Studies into the Reactivity of Frustrated Lewis Pairs Containing N-N Bases with Hydrogen

by

Daniel A. Dalessandro

A thesis submitted in conformity with the requirements for the degree of Master of Science

Department of Chemistry University of Toronto

© Copyright by Daniel A. Dalessandro 2014

ii

Studies into the Reactivity of Frustrated Lewis Pairs Containing

N-N Bases with Hydrogen

Daniel A. Dalessandro

Master of Science

Department of Chemistry

University of Toronto

2014

Abstract

Frustrated Lewis Pairs (FLPs) typically consist of main-group Lewis acids and bases, and can be

used to affect a variety of small molecule activations. Modulation of the base’s identity is of high

interest in our group as this affords the reduction of systems with varying electronic properties.

Such manipulations, for example, have led to the development of reductions of N-heterocycles,

anilines, olefins and C=N bonds. In certain cases, such as hydroaminations, catalytic reduction

was possible. Herein, studies into a novel FLP system containing diazo (N=N) or hydrazine (N-

N)-type bases are presented. Such systems were shown to be effective in activating dihydrogen,

resulting in the hydrogenolysis of the diazene bond. The implications that these observations

have on the development of catalytic systems as well as their broader applications toward their

reactivity with other small molecules will be discussed.

iii

Acknowledgments

Of the many people to thank, I think I am most indebted to my supervisor Prof. Doug Stephan,

without whom I would not have learned the critical skills necessary to be a great chemist. You

were wonderfully patient and accepting of me throughout my time in your lab, and I have grown

immensely as a result, thank-you. Next, I’d like to thank (soon to be Dr.) Tayseer Mahdi, Dr.

Daniel Winkelhaus and Dr. Manuel Pérez Vásquez. Despite the fact that you all had your own

work to do, not once did you hesitate or refuse to assist me when I came to you for help. I wish

you all the luck in the world with the next steps of your lives, wherever it is that you end up next

you’ll surely be great. Also, I’d like to thank Lauren Longobardi, Tayseer Mahdi, Eliar Mosaferi,

Judy Tsao, and July Roy for their editing help. Of course, thank you to Prof. Doug Stephan and

Prof. Datong Song for their assistance in the final edits of my thesis. I’d like to thank all of the

members of my family, in particular my parents, Oronzo and Lori. Last but certainly not least,

I’d like to thank Rosemary Leone for remaining patient and giving me all of the support that I

needed throughout the course of this degree, I love you. To all of the Stephan Group, I know it’s

been a tough year, in more ways than one, and thanks for being there for me whenever I needed

it; you have all played an equal part in who I am and in what I will become.

iv

Table of Contents

Acknowledgments .......................................................................................................................... iii

Table of Contents ........................................................................................................................... iv

List of Tables ................................................................................................................................ vii

List of Figures .............................................................................................................................. viii

List of Schemes .............................................................................................................................. ix

List of Abbreviations and Symbols ............................................................................................... xii

Chapter 1: Introduction .................................................................................................................. 1

1.1 Overview of Lewis Acid-Base Pairs .................................................................................. 1

1.2 Overview of Frustrated Lewis Pairs: Early Developments ................................................ 2

1.3 Toward a Working Description of FLPs ............................................................................ 3

1.4 FLP-Mediated Hydrogenation............................................................................................ 4

1.5 Proposed Mechanism of Hydrogenation by FLPs ............................................................. 6

1.6 Small Molecule Activation with FLPs ............................................................................... 7

1.7 Toward FLPs with N-Containing Lewis Bases ................................................................ 10

1.8 Broader FLP Reactions with N-Containing Bases ........................................................... 12

v

1.9 Scope of Thesis ................................................................................................................ 14

Chapter 2: Azobenzenes as Lewis Bases in FLP-Mediated Hydrogenations ................................ 17

2.1 Reported Reactivity of Azobenzenes: Hydrogenation .................................................... 17

2.2 Project Proposal: FLPs Containing Azobenzene Lewis Bases for Hydrogenation .......... 18

2.3 Results and Discussion ..................................................................................................... 20

2.3.1 Feasibility of Azobenzene as an FLP-Base .......................................................... 20

2.3.2 Reactivity of Azobenzene with Hydrogen at Elevated Temperatures .................. 22

2.3.3 Preliminary Tests into the Reactivity of Azobenzene with Hydrogen ................. 24

2.3.4 Synthesis of Azobenzene Derivatives ................................................................... 25

2.3.5 The Effect of Temperature in the Hydrogenation of Azobenzenes ...................... 27

2.3.6 The Effect of H2 Pressure on Conversion in the Hydrogenation of

Azobenzenes ............................................................................................................ 29

2.3.7 The Effect of a Sterically Encumbered Azobenzene Derivative on

Hydrogenation ......................................................................................................... 33

2.3.8 Mechanistic Insight into the Hydrogenation of Azobenzene ................................ 34

2.3.9 Hydrogenation of a Hydrazine Derivative of Diphenylamine: Results ................ 38

2.3.10 Hydrogenation of a Hydrazine of Diphenylamine: Discussion ............................ 42

vi

2.3.11 Reactivity of an N-N Bond-Containing Compound not derived from Aniline:

Results and Discusison ............................................................................................ 43

2.4 Conclusions ...................................................................................................................... 47

2.5 Future Directions .............................................................................................................. 48

S0 Supporting Information .......................................................................................................... 51

S1 General Information ......................................................................................................... 51

S2 General Procedures for NMR-Scale Hydrogenations ...................................................... 52

S3 General Procedures for Bomb-Scale Hydrogenations ..................................................... 53

S4 General Procedures for Parr®-Facilitated Hydrogenations ............................................. 53

S5 Preparation of Azobenzene Starting Materials ................................................................. 54

S6 Preparation of 1,1,2,2-Tetraphenylhydrazine ................................................................... 55

S7 NMR Data of Azobenzenes .............................................................................................. 56

S8 Hydrogenation Results ...................................................................................................... 66

References ...................................................................................................................................... 97

vii

List of Tables

Table 2.1 Results of hydrogenation trials run at 4 atm. of H2 ...................................................... 30

Table 2.2 Results of hydrogenation trials run at 100 atm. of H2 .................................................. 32

viii

List of Figures

Figure 1.1 Schematic representation of a Frustrated Lewis Pair .................................................... 4

Figure 1.2 Computational model of hydrogen activation using a phosphine-borane

FLP complex ................................................................................................................................... 7

Figure 1.3 Project proposal using diazenes in hydrogenations and addition reactions ................ 16

Figure 2.1 11

B NMR spectrum of the azobenzene-B(C6F5)3 FLP pair under H2 at elevated

temperatures .................................................................................................................................. 22

Figure 2.2 POV-ray depiction of dicyclohexylammonium hydridoborate ................................... 42

Figure 2.3 Various cinnolines and cinnolinium salts and their pharmaceutical/industrial

applications ................................................................................................................................... 49

ix

List of Schemes

Scheme 1.1.0 Classical Lewis acid-base adduct formation ............................................................ 1

Scheme 1.1.1 Selected Examples of reactivity which are inconsistent with Lewis’ theory ........... 3

Scheme 1.1.2 Earliest example of reversible metal-free dihydrogen activation by a Frustrated

Lewis Pair ....................................................................................................................................... 5

Scheme 1.1.3 Selected examples of hydrogen activation using bulky

phosphine-borane pairs ................................................................................................................... 5

Scheme 1.1.4 Selected examples of hydrogen activation with FLPs ............................................. 8

Scheme 1.1.5 Reactivity of olefins and alkynes with various FLP complexes .............................. 9

Scheme 1.1.6 FLP-mediated ring opening transformations .......................................................... 10

Scheme 1.1.7 Reduction of an (E)-disubstituted olefin using FLP-catalysis ............................... 10

Scheme 1.1.8 Various examples of small molecule activation using amine-borane FLP

complexes ..................................................................................................................................... 11

Scheme 1.1.9 Examples of N-containing bases in multicomponent FLP transformations ........... 12

Scheme 1.2.0 Selected examples outlining the broad scope of N-base FLP chemistry ............... 13

Scheme 1.2.1 Proposed mechanism of enamine formation with 1,3-proton transfer from a

trans-alkenylborate ........................................................................................................................ 14

Scheme 1.2.2 Synthesis of complex heterocyclic systems via additions to alkynes .................... 15

x

Scheme 2.1.0 Overview of the various methods to hydrogenate azobenzene .............................. 18

Scheme 2.1.1 Modulation of the Lewis Acid strength in FLPs .................................................... 19

Scheme 2.1.2 Proposed product from hydrogen activation using an azobenzene-B(C6F5)3 FLP

complex ......................................................................................................................................... 20

Scheme 2.1.3 Characterization of the azobenzene-B(C6F5)3 FLP complex ................................. 21

Scheme 2.1.4 Activation of B(C6F5)3 by imidazole in the presence of protic amines .................. 23

Scheme 2.1.5 Activation of B(C6F5)3 by azobenzene and its reduced derivatives at elevated

temperatures .................................................................................................................................. 24

Scheme 2.1.6 Product of hydrogenation of azobenzene and its derivatives is consistent with

an aniline-B(C6F5)3 adduct ............................................................................................................ 25

Scheme 2.1.7 Two protocols used to synthesize azobenzene derivatives, showing the CuBr-

catalyzed method to be superior ................................................................................................... 26

Scheme 2.1.8 Variable-Temperature experiments found that the optimal temperature of

hydrogenation was 40 °C .............................................................................................................. 28

Scheme 2.1.9 Results of the hydrogenation trials with derivative the tetrakis(iPr) diazene

derivative ....................................................................................................................................... 34

Scheme 2.2.0 Mechanism of FLP-catalyzed reduction of imines using a borenium cation-FLP

complex ......................................................................................................................................... 35

xi

Scheme 2.2.1 Proposed mechanism of FLP-mediated hydrogenation of azobenzene to

aniline ........................................................................................................................................... 36

Scheme 2.2.2 Cu(I) mediated synthesis of 1,1,2,2-Tetraphenylhydrazine ................................... 38

Scheme 2.2.3 Hydrogenation results of 1,1,2,2-Tetraphenylhydrazine at elevated temperature

and at one day intervals ................................................................................................................. 40

Scheme 2.2.4 Proposed mechanism of aromatic hydrogenation of diphenylamine by

Stephan et. al. ................................................................................................................................ 43

Scheme 2.2.5 Hydrogenation of phthalazine ................................................................................ 45

Scheme 2.2.6 The synthesis of N-heterocycles via FLP-mediated

intramolecular cyclization .............................................................................................................. 48

Scheme 2.2.7 Cinnolines can be accessed from a diazene-anchored aromatic alkyne .................. 50

xii

List of Abbreviations and Symbols

° degrees

Å Angstrom, 10-10

m

δ chemical shift, ppm

∆ p-m Change in δ between para-fluorine and meta-fluorine signals in 19

F NMR

~ Approximately

Ar Aryl

Azobenzene C12H12N2, or its derivatives

Br broad

BCF B(C6F5)3, tris(pentafluorophenylborane)

C Celsius

Cy Cyclohexyl

d doublet

DCM dichloromethane, methylene chloride, CH2Cl2

Diazene azobenzene (C12H12N2), or its derivatives

eq. Equivalents

Et ethyl, C2H5

Et2O diethyl ether, O(C2H5)2

et al. and others

FLP Frustrated lewis Pair

xiii

FT Fourier transform

G gram

H hour

Hz Hertz, s-1

iPr isopropyl, CH(CH3)2

J Symbol for coupling constant, Hz

kcal kilocalorie

lut 2,6-lutidine, C7H9N

m multiplet

m meta

Me methyl, CH3

Mg milligram

MHz megahertz, 106 s

-1

min minute

mL milliliter(s), 10-3

L

mmol millimole(s), 10-3

mol

mol mole(s)

MW molecular weight, g/mol

nBu n-butyl, C4H9

NMR nuclear magnetic resonance

xiv

NR no reaction

o ortho

p para

Ph phenyl, C6H5

Ppm parts per million, 10-6

py pyridine

q quartet

rt room temperature

s singlet

t triplet

tBu tert-butyl, C4H9

THF tetrahydrofuran, C4H8O

TMP 2,2,6,6-tetramethylpiperidine

TPH Tetraphenylhydrazine

vs. Versus

1

Chapter 1 Introduction

1.1 Overview of Lewis Acid-Base Pairs

Lewis acids and bases are ubiquitous components in synthetic chemistry. First described by

Gilbert Lewis in 1923, he differentiated them according to their ability to either donate or accept

lone-pairs of electrons. The former is descriptive of a Lewis base, while the latter of a Lewis acid

(Scheme 1.1.0).1 The International Union of Pure and Applied Chemists (IUPAC) have since

expanded this to a more general definition, where it stipulates that a zwitterionic Lewis adduct is

formed following the transfer of a lone pair of electrons from a Lewis base to the empty low-

energy orbitals of a Lewis acid.2 Upon adduct formation, the Lewis acid experiences an overall

reduction in bond angles to accommodate coordination.2 Such is the case with boron-nitrogen

adducts, in particular, which pertains to this thesis.3 Boranes are trigonal planar species with

empty p-orbitals and thus behave as Lewis acids. Upon interaction with a lone-pair from a Lewis

base such as nitrogen, it undergoes a pyramidalization to compensate for added steric strain.3 In

certain systems where such quenching is precluded, then a reformulation of Lewis’ theory was

required. The contents of this chapter will therefore discuss this active area of research.

Scheme 1.1.0 Classical Lewis acid-base adduct formation.

2

1.2 Overview of Frustrated Lewis Pairs: Early Developments

Despite the applicability of Lewis’ postulate of acids and bases, exceptions to the theory arose

upon further exploration. The earliest of which was reported by H.C. Brown and coworkers in

1942. They discovered that a combination of 2,6-lutidine and trimethylborane resulted in no

reaction, despite the apparently accessible filled and empty orbitals (Scheme 1.2).4 Interestingly,

when a less sterically demanding acid was mixed with 2,6-lutidine the anticipated classical

Lewis acid-base adduct was observed.4 Shortly after, Wittig and Benz described similar

behaviour, where benzyne (generated in situ from o-fluorobromobenzene) reacted with a mixture

of triphenylborane and the acid triphenylphosphine to yield an o-phenylene bridged

phosphoniumborate (Scheme 1.1.1).5-6

Subsequent work by Tochtermann in 1966 described the

1,2-addition of the trityl cation and triphenylborane with butadiene to form the 1,2-addition

product (Scheme 1.1.1).7 Both Wittig and Tochtermann acknowledged that in cases where the

Lewis acid and base pair are sterically congested, formation of the classical Lewis adduct is

precluded. Tocthermann further described such sterically un-quenched Lewis acid-base pairs as

“antagonishtisches Paar”.7

3

Scheme 1.1.1 Selected examples of reactivity which are inconsistent with Lewis’ original theory.

1.3 Toward a Working Description of FLPs

Given the discovery of novel types of Lewis acid and base interactions, recent work has focused

on the exploration and exploitation of their chemistry. Pioneering work by Stephan and

coworkers in 2006 challenged Lewis’ long-established axiom.8-10

Systems in which adduct

formation was precluded due to the presence of a bulky Lewis acid and base were analyzed and

found to mimic the chemistry of transition metals and activate small molecules (Figure 1.1).

Stephan and coworkers described such systems as “Frustrated Lewis Pairs” (FLP).8-10

Later work

divulged that it is more apt to describe these using a continuum, whereby even compounds where

adduct formation is weak and reversible can be exploited in FLP chemistry.8 Therefore, there

existed a potential for FLPs to be used in analogous-to-transition metal reactions.

4

Figure 1.1 Schematic representation of a Frustrated Lewis Pair.

1.4 FLP-Mediated Hydrogenation

Following the initial discussion of FLPs, Stephan and Erker have broadened the reactivity of

these systems. In 2006 Stephan and coworkers reported the first example of metal-free reversible

activation of dihydrogen utilizing a novel FLP system (Scheme 1.1.2).11

In this work, Lewis acid

and base functionalities were incorporated into the same molecule by reaction of

dimesitylphosphine with tris(pentafluorophenyl)borane (B(C6F5)3) (Scheme 1.1.2). 11

The

subsequent zwitterionic phosphonium-borate, (Mes)2PH(C6F4)BF(C6F5)2, was formed via a para-

nucleophilic aromatic substitution on a pentafluorophenyl ring of B(C6F5)3 affecting fluoride

migration to the boron center (Scheme 1.1.2).11

Subsequent reaction of this salt with

chlorodimethylsilane resulted in a fluoride-hydride exchange yielding the hydrogenated salt,

(Mes)2PH(C6F4)BH(C6F5)2.11

It was also found that heating the salt above 100 °C resulted in the

liberation of H2, forming the phosphinoborane (Mes)2P(C6F4)B(C6F5)2. This was confirmed

separately by reaction of the phosphonium-borate with an equivalent of a Grignard reagent.

Reversibility was uncovered upon reaction of the phosphionoborane with hydrogen gas which re-

formed the hydrogen-activated product.11

5

Scheme 1.1.2 Earliest example of reversible metal-free dihydrogen activation by a Frustrated

Lewis Pair.

Subsequent work probed the generality of the FLP-mediated heterolytic cleavage of dihydrogen

(Scheme 1.1.3). To this end, intermolecular-type systems using bulky phosphines, R3P (R = tBu,

C6H2Me3) mixed with B(C6F5)3 were probed.11

Satisfyingly, no acid/base neutralization was

observed in such systems. Also, in exposing them to hydrogen gas at room temperature, they

showed facile cleavage of dihydrogen forming the respective phosphonium hydridoborate salts

(Scheme 1.1.3).11

Similar reactivity was also observed upon modulating the Lewis acid using

triphenylborane (Scheme 1.1.3).

Scheme 1.1.3 Selected examples of hydrogen activation with bulky phosphine-borane pairs.

6

Although H2 activation with BPh3 was observed, the corresponding salt was isolated in only a

33% yield.12

Additionally, no reaction with dihydrogen was observed with less basic phosphines.

Based on these data, Stephan and coworkers concluded that FLP reactivity is determined by a

combination of both the steric and electronic properties of the interacting acid and base .9,10

This

proved to be quite insightful in understanding the range of Lewis acidity and basicity needed in

order to cleave the dihydrogen bond.

1.5 Proposed Mechanism of Hydrogenation by FLPs

Early reports by the group of Stephan and co-workers into the mechanism of dihydrogen

activation revealed that intramolecular activation is the initial sep.13

It was originally believed

that this was consistent with first-order kinetics. However this kinetic data was later determined

to be misleading as the back-reaction resulting in hydrogen loss is facile.14

Regardless, detailed

kinetic investigations remained elusive due to the difficulty in controlling hydrogen

concentrations in solution.8

Efforts next turned toward computational studies in order to provide insight into the molecularity

of dihydrogen activation.15

Early theoretical investigations into the interaction of BH3 and H2

suggested that dihydrogen activation is initiated by the Lewis acid leading to protonation of the

Lewis base, consistent with a third-order process.15

This postulate was also deemed

unreasonable, largely due to empirical evidence which demonstrated that phosphine Lewis bases

do interact with H2 via a nucleophilic attack in an end-on interaction.

16

Studies by the groups of Papai and Grimme further elucidated the currently-accepted mechanism

of heterolytic H2 activation by FLPs (Figure 1.2) .17

The method of activation involved formation

7

of an “encounter complex”, wherein a molecule of hydrogen is trapped in a pocket between the

FLP pair which is unable to form a dative bond due to steric congestion.17

The dihydrogen

subsequently orients itself in such a fashion between the donor and acceptor sites that heterolytic

cleavage of the H-H bond follows.17-19

Figure 1.2 Computational model of hydrogen activation using a phosphine-borane FLP complex.

1.6 Small Molecule Activation with FLPs

Work into FLP chemistry subsequently investigated the scope of reactivity that they can

facilitate. Collaborative efforts from the groups of Stephan and Erker showed the activation and

insertion of CO2, NO2, SO2 and N2O was facile using B(C6F5)3 and a bulky Lewis base (Scheme

1.1.4).13, 14; 21

This reactivity was shown to be possible using both the traditional bimolecular FLP

system, PtBu3/B(C6F5)3 developed by Stephan, or the ethyl-linked P/B systems developed by

Erker. The mechanism is believed to proceed from formation of the FLP encounter complex,

similar to that proposed for H2 activation (see Figure 1.2).

2.24 Å

0.79 Å

1.74 Å

8

Scheme 1.1.4 Selected examples of small molecule activation with FLPs.

It was also shown that FLPs can add across unsaturated species including terminal alkenes and

alkynes (Scheme 1.1.5).22-23

In cases of terminal alkynes, the sensitivity of the system to

electronics plays an important role. When using a stronger base such as PtBu3, deprotonation

predominates. The addition product is observed when using a milder base such as P(o-tol)3. This

sensitivity is not observed with internal and terminal alkenes, where only the addition product is

observed.24-26

9

Scheme 1.1.5 Reactivity of olefins and alkynes with various FLP complexes.

Early reports by Wittig and Rückert, which showed that the trityl anion could affect the ring-

opening of THF, inspired the investigation of FLPs in similar chemistry (Scheme 1.1.6).27

Indeed, later studies by Breen and Stephan showed that the treatment of [ZrCl4(THF)2] with

PCy3 gave the salt, [{Cl4Zr(μ-O-(CH2)4PCy3)}2] (Scheme 1.1.6).27

Analogous combinations

showed similar reactivity in particular with phosphorous\based Lewis bases. Smaller bases were

required for such a ring-opening reaction, such as dimesityl phosphine (Mes2PH), di-tert-

butylphosphine (tBu2PH), for example (Scheme 1.1.6).

28

10

Scheme 1.1.6 FLP-mediated ring opening transformations.

1.7 Toward FLPs with N-Containing Lewis Bases

Considering most of the initial FLP work was based primarily on phosphine and perfluorinated

borane pairs, subsequent work has focused on the development and advancement of their

chemistry. Indeed, it was discovered that catalytic hydrogenation of various polar substrates was

facile using intramolecular phosphine-borane FLP complexes (Scheme 1.1.7).22

Scheme 1.1.7 Reduction of an (E)-disubstituted olefin using FLP-catalysis.

11

While synthetically useful, the analogous chemistry using diverse Lewis bases other than

phosphorous has been less explored.8 Nitrogen-containing systems, in particular, are

synthetically and commercially advantageous as amines are ubiquitous components of synthetic

and process chemistry. Early work investigating bulky amine-containing bases, such as

diisopropyl amine and 2,2,6,6-tetramethylpiperidine, reported that they undergo facile hydrogen

activation to produce the corresponding ammonium hydridoborate salts (Scheme 1.1.8). In the

latter case, the salt could be reacted further with an equivalent of carbon dioxide to produce the

intramolecular boron carboxylate.30-32

Scheme 1.1.8 Various examples of small molecule activation using amine-borane FLP

complexes.

12

1.8 Broader FLP Reactions with N-Containing Bases

Stephan and coworkers investigated the amines and imines in FLP reactions where they behaved

as both a base and a substrate. It was observed that a variety of bulky imines could undergo

catalytic hydrogenations, yielding the corresponding amine (Scheme 1.1.9). Such work was later

expanded by Stephan and Erker to include synthesis of a variety ammonium alkynylborate and

ammonium alkenylborate salts, complementing the phosphorous-boron FLP systems (Scheme

1.1.9).32,33

Scheme 1.1.9 Examples of N-containing bases in multicomponent FLP transformations.

A remarkable discovery in 2012 provided support for the use of N-containing bases in FLP

chemistry. Early reports using bulky N-substituted aniline and 2,6-disubstituted pyridyl

derivatives showed that hydrogen could be predictably activated by such substrates (Scheme

13

1.2.0).35

Under more forcing conditions, with a stoichiometric amount of B(C6F5)3, it was

discovered that the aromatic moiety of such amines could be reduced to the cyclohexyl- and

piperidyl-derivatives, respectively.34,35

Scheme 1.2.0 Selected examples outlining the broad scope of N-base FLP chemistry.

The most recent additions to the library of FLPs containing N-bases were a series of catalytic

hydroaminations. Such transformations were previously only effected using metal-based

protocols90

whereas metal-free protocols remained sparse.36

Stephan reported that catalytic

B(C6F5)3 promoted the addition of aryl amines to alkynes to the corresponding amine derivatives

(Scheme 1.2.0).36

The proposed mechanism is based upon the observation that catalysis only

occurred upon slow addition of the alkyne (Scheme 1.2.1).36

Formation of the amine-borane FLP

is reversible and alkyne activation occurs with a free equivalent of the borane. The resultant

proton from the zwitterionic arylammonium intermediate is acidic and undergoes a 1,3-proton

14

migration to give the free enamine, liberating an equivalent of the borane to effect further

catalysis.

Scheme 1.2.1 Proposed mechanism of enamine formation with 1,3-proton transfer from a trans-

alkenylborate.

1.9 Scope of Thesis

Our group had considerable interest in broadening the scope of N-bases that could be used in

FLP chemistry. For example, early reports by Erker and coworkers reacted thioethers and bulky

phosphine-anchored terminal alkynes with B(C6F5)3 to give a variety of heterocycles. (Scheme

1.2.2).37,38

These reactions generally proceed through 1,2-addition of the Lewis-base and

B(C6F5)3 to an alkynl fragment. Interestingly, products of this nature were not reported to be

accessible with amine or imine-based FLPs by Stephan and coworkers. The impetus for the

current project stemmed from using novel N-containing compounds as Lewis-bases in FLPs.

Immediate interest was placed upon the azobenzene family (PhN=NPh) for several reasons:

15

FLPs containing bases with the diazo (N=N) moiety have never been explored, they are

commercially available and economical, and they contain two Lewis-basic nitrogen centers free

to participate in FLP chemistry.

Scheme 1.2.2 Synthesis of complex heterocyclic systems via additions to alkynes.

Initially, we needed to understand the strength of the interaction between azobenzene and

B(C6F5)3. Therefore, we also investigated the FLP reactivity of these novel N-N-containing

substrates with H2 in order to develop a detailed understanding of their electronic and steric

characteristics, as FLP-containing N-bases of this nature are uncommon. In doing so, one can

envision tuning and exploiting these factors in order to probe their viability in additions to

unsaturated compounds (Figure 1.3).39

16

Figure 1.3 Project proposal using azobenzenes in hydrogenations and addition reactions.

17

Chapter 2 Azobenzenes as Lewis Bases in FLP-Mediated Hydrogenations

2.1 Reported Reactivity of Azobenzenes: Hydrogenation

There are several literature records on the hydrogenation of azobenzene derivatives. The first

report by Gitua and Eisch used a Ti(IV) catalyst followed by a hydrolytic work-up to achieve the

addition of one equivalent of hydrogen across the N=N moiety of azobenzenes, giving the

hydrazine product (Scheme 2.1.0).55

Later studies by Plietker and Beller used a Ru(II) catalyst

followed by aqueous work-up and achieved the full reduction of azobenzene to the respective

aniline.56-58

Subsequent work by other authors focused on developing metal-free analogues to

this chemistry. Zhen et. al. found that using chitosan-supported formate and magnesium followed

by aqueous work-up could affect complete reduction of azobenzene to aniline.59

A later report by

Kinjo et. al, showed that the reduction to of azobenzene to hydrazine was facile using ammonia-

borane as the source of hydrogen and a planar N-heterocyclic phosphane as the catalyst.60

18

Scheme 2.1.0 Overview of the various methods to hydrogenate azobenzene.

2.2 Project Proposal: FLPs Containing Azobenzene Lewis Bases for Hydrogenation

For some time now, interest in FLP-mediated hydrogen activation has been rooted in catalytic

hydrogenations of unsaturated organic compounds, which is an important industrial process.

Work by our group has been focused upon the investigation of FLPs containing N-bases and

their feasibility for use catalytic hydrogenations. One account by Farrell and Stephan showed that

a borenium ion was effective toward the catalytic hydrogenation of a variety of imine-containing

19

substrates (Scheme 2.1.1).61

Further investigation by both the Stephan and the Erker group have

found that the Lewis acidity of the alkenylborane resulting from 1,1-carboboration of B(C6F5)3

and (n-C3H7)C≡C(n-C3H7) is lower than B(C6F5)3, which facilitated the catalytic reduction of

otherwise inert enone-substrates.62

It was noted that modulation of the Lewis-acid’s strength was

synthetically challenging, in general.61

In contrast, modulation of the basicity of FLPs containing

nitrogen was relatively facile (see: Chapters 1.7-1.8).33-37

Scheme 2.1.1 Modulation of the Lewis Acid strength in FLPs.

Provided the reduced Lewis basicity of the azobenzenes relative to aniline, and their established

reactivity toward hydrogen,55-59

the azobenzene family’s ability to activate dihydrogen using

FLP-type mechanisms will be investigated (Scheme 2.1.2).89

This substrate would be a

noteworthy addition to the scope of FLP chemistry in that dihydrogen activation has only been

observed in C-X type bonds (X = N, S, O), but never N=N bonds.67,68

Secondly, the highly

protic diazenium cation that would result from dihydrogen activation could be used toward the

catalytic reduction of otherwise stable unsaturated substrates.

20

Scheme 2.1.2 Proposed product from hydrogen activation using an azobenzene-B(C6F5)3 FLP

complex.

2.3 Results and Discussion

2.3.1 Feasibility of Azobenzene as an FLP-Base

Addition of a solution of (E)-diphenylazobenzene (azobenzene) to an equimolar solution of

B(C6F5)3 in toluene at room temperature resulted in minimal adduct formation (Scheme 2.1.3).

Analysis of the 19

F NMR spectrum showed two sets of peaks, one set at -132.6 ppm, -154.5

ppm and -161.7 ppm corresponded to the o-C6F5, p-C6F5 and m-C6F5 fluorine atoms of the

azobenzene-B(C6F5)3 adduct, respectively (Scheme 2.1.3). The other set of peaks at -127.3

ppm, -141.9 ppm and -159.4 ppm, correspond to B(C6F5)3 (Scheme 2.1.3). Relative integration of

these peaks indicated that they were present in a 1:23.5 ratio, respectively. The resonances

attributed to the m-C6F5 and p-C6F5 fluorine atoms show a reduction in their separation from 15.8

ppm to 7.2 ppm, indicating pyramidalization of B(C6F5)3.8 Lastly a sharp peak in the ~ -3 ppm

region of the 11

B NMR spectrum reflected the four-coordinate boron of the adduct, while a peak

at ~ 55 ppm was characteristic of the three-coordinate boron of B(C6F5)3. These data led us to

conclude that in solution we were observing both free B(C6F5)3 as well as a weakly bound adduct

between azobenzene and B(C6F5)3.

21

Literature work reveals that most aromatic amines form weak adducts with B(C6F5)3, the most

similar example to the present system being N-methylaniline.33

Based on our observations we

believe that (E)-diphenylazobenzene interacts similarly with B(C6F5)3. The weak interaction is

perhaps due to delocalization of nitrogen’s lone-pair around the adjacent π-system of the

aromatic rings.51,52

Scheme 2.1.3 Characterization of the azobenzene-B(C6F5)3 FLP complex. Solvent: CD2Cl2,

Spectrometer: 400 MHz.

~96% ~4%

11B NMR 19

F NMR

* **

** ** **

**

*

*

*

*

22

2.3.2 Reactivity of Azobenzene with Hydrogen at Elevated Temperatures

The reactivity of this weak FLP-complex toward dihydrogen was probed next. Addition of

azobenzene and B(C6F5)3 in 1:1 molar quantities under H2 in bromobenzene-d5 followed by

heating at 110 °C for two days resulted in a mixture of products. The corresponding 1H NMR

spectrum showed two peaks at 7.94 ppm and 7.32 ppm in the aromatic region with a relative

integration of 2:3, corresponding to the azobenzene starting material. Additionally, there was a

complex multiplet in the 1H NMR spectrum present in minor quantities at 6.31 ppm which was

believed to be C6F5H. This was confirmed through analysis of the 19

F NMR spectrum which

showed peaks at -138.1 ppm, -154.8 ppm and -161.5 ppm, which is consistent with literature

values for C6F5H.73

The 11

B NMR spectrum showed the presence of two broad singlet peaks at

60.4 ppm and 34.5 ppm, corresponding to free B(C6F5)3 and an unknown three-coordinate

borane, respectively (Figure 2.1). The presence of B(C6F5)3 was confirmed by 19

F NMR

spectroscopy, with three peaks at -127.3 ppm, -141.9 and -159.3 ppm.88

Figure 2.1 11

B NMR spectrum of the azobenzene-B(C6F5)3 FLP pair under H2 at elevated

temperatures.

23

The 19

F NMR spectrum also showed three other signals, occurring at -131.2 ppm,

-154.9 ppm, -161.9, with relative integrations of 4:2:4 for a total of ten fluorine atoms. These

data, combined with our 11

B NMR spectrum are in fact consistent with an amido-borane complex

of the general type R2N-B(C6F5)2. It was already known based on work by Stephan and

coworkers, that imidazole in catalytic quantities in the presence of a protic amines of the type,

R1R2NH, and B(C6F5)3 can cleave a pentafluorophenyl ring from B(C6F5)3 to form C6F5H and a

stable amido-borane species (Scheme 2.1.4).8,73,74

.

Scheme 2.1.4 Activation of B(C6F5)3 by imidazole in the presence of protic amines.

It was believed that this reaction proceeds through initial protonation of the imidazole by the

amine substrate forming an imidazolium species. This then protonates a C6F5 ring of B(C6F5)3 to

produce C6F5H, amido-borane and regenerating the imidazole (Scheme 2.1.4). We propose that

a similar reaction pathway is likely with our system, as the azobenzenes are relatively acidic (pKa

~ 3.5) and may be able to protonate a C6F5 ring of B(C6F5)3 in the absence of imidazole.89

This

was spectroscopically confirmed by both the presence of three-coordinate boron as well as

C6F5H (Figure 2.1). Also, when the corresponding aniline and hydrazine were subjected to

similar conditions, the same three-coordinate borane was observed (Scheme 2.1.5). Lastly, as

these boranes have diminished Lewis acidity at the boron center, it was determined that

hydrogenations at elevated temperatures were not feasible.

24

Scheme 2.1.5 Activation of B(C6F5)3 by azobenzene and its reduced derivatives at elevated

temperatures.

2.3.3 Preliminary Tests into the Reactivity of Azobenzene with Hydrogen

Subsequent work aimed at determining the optimal set of conditions in which hydrogen

activation using azobenzene as an FLP-base could be achieved. Azobenzene and B(C6F5)3 were

stirred in 1:2 molar ratios in hexanes for two days under 4 atm. of H2 at room temperature. After

this period, a fine yellow powder was observed to precipitate from solution. The 1H NMR

spectrum of this powder revealed a highly pure product with multiplets at 6.55 ppm and 6.33

ppm and a broad singlet at 5.81 ppm. These had relative integrations of 3:2:2, respectively. 11

B

NMR spectral data indicated the complete consumption of B(C6F5)3 and showed a sharp singlet

at -5.69 ppm. Additionally, the 19

F NMR spectrum showed resonances at -133.2, -154.9 and -

162.5 ppm; the reduced meta-para gap from 17.3 ppm in free B(C6F5)3 to 7.1 ppm in this species

is indicative of the B(C6F5)3 fragment in a four-coordinate environment.

This major product was hypothesized to be an aniline-borane adduct, suggesting cleavage of the

N=N bond of azobenzene had occurred. To confirm this, two tests were conducted (Scheme

25

2.1.6). Firstly, when the corresponding diphenylhydrazine (1b) was subjected to similar

hydrogenation conditions, identical 1H NMR,

11B NMR and

19F NMR spectra were obtained

(Scheme 2.1.6). Additionally, when the corresponding aniline and B(C6F5)3 were mixed in a 1:1

ratio, the NMR data of the resulting aniline-borane salt was also found to be consistent with the

product of the azobenzene-B(C6F5)3 hydrogenation described above (Scheme 2.1.6). As such, we

concluded that the azobenzene was undergoing reduction with two equivalents of H2 to produce

1a (Scheme 2.1.6). The mechanism of hydrogenation will be expanded on in Chapter 2.28.

Scheme 2.1.6 The product of azobenzene and diphenylhydrazine hydrogenations was consistent

with an aniline-B(C6F5)3 adduct.

2.3.4 Synthesis of Azobenzene Derivatives

A facile synthetic approach of the functionalized azobenzenes was required in order to better

understand the scope of this reduction.64-67

It should be noted that such compounds were not

commercially available, and the only way to access them without having to work with explosive

and hazardous diazonium precursors was through a metal-mediated oxidative dehydrogenative

1a 1b

26

coupling reaction.69-71

Two such protocols were investigated: a stoichiometric Pb(OAc)2-

mediated coupling, and a CuBr-catalyzed protocol (Scheme 2.1.7).69-72

Scheme 2.1.7 Two protocols used to synthesize azobenzene derivatives, showing the CuBr-

catalyzed method to be superior.

The stoichiometric Pb(OAc)2-mediated coupling protocol suffered from low yields of <10%.

Also the scope of azobenzenes that could be made with this protocol was also quite limited. The

much milder, high-yielding CuBr-catalyzed protocol was thus chosen as it would allow for the

synthesis of a wide variety of azobenzenes (Scheme 2.1.7). In this fashion, the following

compounds 1b-i were prepared.

- Poor yields (< 10%). - Smaller library of

derivatives

- No aqueous work-up required.

- Better yields (> 70%). - Catalytic method - Access to a wider library

of diazenes.

27

2.3.5 The Effect of Temperature in the Hydrogenation of Azobenzenes

At this point, it was of interest to next determine the optimal temperature in which to conduct the

hydrogenation of the azobenzene derivatives. In order to achieve this, azobenzene derivative 1c

and B(C6F5)3 were mixed in a 1:2 stoichiometric ratio and reacted for a total of eleven days: five

days at room temperature and six days at 40 °C. The reaction progress then monitored by 1H

NMR, 11

B NMR and 19

F NMR spectroscopy. Note that these tests were conducted with

derivative 1c, as the corresponding hydrazine (2c) and aniline-borane (3c) were easily

distinguishable by 1H NMR spectroscopy. The aromatic peaks for 1c appear as two downfield

doublets with shifts of 7.91 ppm and 7.53 ppm in the 1H NMR spectrum. In comparison, the

aromatic resonances corresponding to the aniline-borane adduct, 2c, show as doublets with shifts

of 7.30 ppm and 7.03 ppm, while the N-H resonance appears as a broad singlet at 6.90 ppm,

respectively. Lastly, the aromatic peaks for the hydrazine derivative, 3c, appear at 7.26 ppm and

7.17 ppm, while the N-H proton occurred as a doublet at 6.60 ppm. Knowing this, the relative

amounts of each could be determined by integration of the 1H NMR spectra (Scheme 2.1.8).

28

Scheme 2.1.8 Variable-Temperature experiments found that the optimal temperature of

hydrogenation was 40 °C.

After reacting at room temperature for five days, the resultant mixture consisted in 28% of the of

starting material, 1c. The remainder of the mixture consisted of 43% of the aniline-borane adduct

(3e), and 29% corresponded to the intermediate hydrazine (3c), although whether it interacted

with B(C6F5)3 was unclear. Increasing the temperature to 40 °C increased the consumption of 1c

to 99% after seven days, with no evidence of C6F5H or an amido-borane adduct. Conversion to

3c only increased slightly to 63%, while the hydrazine 2c was present in 36% yield. On further

reaction, the yield of the aniline-borane only increased marginally with time.

Time Temp.

(°C)

25 3 d

5 d 25

40 7 d

11 d 40

1c 1c

3c 3c

3c 2c

2c

3c

1c 1

H NMR

2c

29

Analysis of the corresponding 11

B NMR and 19

F NMR spectra suggested that consumption of

B(C6F5)3 was not complete. For example, two peaks in the 11

B NMR spectrum were observed at

59.3 and -5.6 ppm, reflective of free B(C6F5)3 and a nitrogen-boron adduct. The former peak

persisted throughout the course of the reaction, confirming that unreacted B(C6F5)3 was present

in solution. Analysis of the 19

F NMR spectrum revealed two sets of peaks: one at -128.2 ppm, -

143.9 ppm and -161.2 ppm, corresponding to free B(C6F5)3, while the other occurred at -133.8

ppm, -156.1 ppm and -163.0 ppm corresponding again to a nitrogen-B(C6F5)3 adduct. It is

known that diphenylhydrazine, under elevated temperatures can cleave a C6F5 ring of B(C6F5)3 to

form an amido-borane species (Shceme 2.6). This process requires adduct formation between the

N-center of the hydrazine and the borane; therefore it is possible that formation of an adduct

between 2c and B(C6F5)3 occurred. However, as evidenced by the persistence of free B(C6F5)3

solution, we believe relative to the less sterically encumbered N-center of aniline, 3c, that

interaction of hydrazine 2c with the borane was weaker. Further work into clarifying the strength

of the hydrazine-B(C6F5)3 is required.

2.3.6 The Effect of H2 Pressure on Conversion in the Hydrogenation of Azobenzenes

Subsequent efforts focused on forcing the complete conversion of azobenzene to the aniline-

borane adduct. To attempt this, the reaction was conducted at 40 °C with two equivalents of

B(C6F5)3. Also, dihydrogen pressures were increased to 4 atm. and the reaction was scaled-up to

0.24 mmol from 0.05 mmol. The results of these experiments are shown in Table 2.1.

30

While consumption of the starting azobenzenes was nearly quantitative for all of the attempts,

conversion to the fully reduced aniline-borane adducts (3c-f) was unsatisfactory, with one

exception: the para-fluorine substituted aniline-borane adduct 3b was the only product observed

following hydrogenation. This was determined by 1H NMR spectroscopy, which showed two

broad multiplets at 7.12-6.95 ppm and 6.95-6.81 ppm with relative integrations of 2:1, reflective

of the aromatic: N-H proton resonances. The 19

F NMR spectrum showed four distinct resonances

at -111.8 ppm, -133.8 ppm, -156.1 ppm, and -163.1 ppm (meta-para gap of ~ 6.7 ppm) with

relative integrations of 1:6:3:6 corresponding to the p-F, o-C6F5, p-C6F5 and m-C6F5 fluorine

atoms, respectively. Also, the 11

B NMR spectrum showed a sharp singlet peak at -6.0 ppm as

R 1(%) 2(%)* 3(%)*

p-F (1b) 0 0 (2b) 100 (3b)

p-Cl (1c) 1 29 (2c) 70 (3c)

p-Br (1d) 20 20 (2d) 60 (3d)

p-iPr (1e) 12 32 (2e) 56 (3e)

p-tBu (1f) 18 28 (2f) 54 (3f)

m-CH3 (1g) N/A N/A N/A

C6F5** (1h) N.R. - -

Table 2.1 Results of experiments run at 4 atm. of hydrogen with preliminary yields. *Results

reported as ratios by 1H NMR ** No conversion was also observed at 110

°C.

1 2 3

31

well as a peak at 55 ppm, confirming the presence of an aniline-borane adduct and free B(C6F5)3

in ratios of approximately 1:2, respectively.

The para-substituted azobenzene derivatives other than 1b gave lower overall aniline-borane

ratios (see S8 of the supplementary information for details). For example, ratios were 70%, 60%,

54% and 56% determined by 1H NMR spectroscopy for aniline-borane adducts 3c-3f,

respectively. Therefore, there was no significant difference in the hydrazine:aniline-borane yields

moving from para-substituted electron-withdrawing to para-substituted electron-donating

groups. Also, a complex mixture of products was observed for the bis(m-(CH3)) azobenzene

derivative, 1g by 1H NMR spectroscopy. This will be expanded upon later in this chapter.

Lastly, the highly electron-deficient derivative, 1h, was not observed to interact with B(C6F5)3 by

19F NMR and

11B NMR spectroscopy, with only free B(C6F5)3 present in solution. As a result, at

40 °C under hydrogenation conditions this derivative was not able to activate dihydrogen.

Elevating the temperature to 110 °C resulted in mainly C6F5H and an amino-borane (three-

coordinate) present by 1H NMR,

11B NMR and

19F NMR spectroscopy, respectively.

Next, the effect that even greater hydrogen pressures had on conversion to the aniline-borane

species 3 was probed. The results from reacting the azobenzene derivatives with B(C6F5)3 at

pressures of 100 atm. for two days at 40 °C in CH2Cl2 are shown in Table 2.2.

32

Slight improvements in ratios were observed for adducts 3c-3f. Our most interesting observation

came with the derivative 1a, where a decrease in yield of the adduct 3b was observed relative to

the low-pressure hydrogenation runs. However, the reason for this was not clear and further trials

are necessary to elucidate the cause. Also, derivative 1h again gave recovery of mostly starting

material with no conversion toward either the hydrazine or the aniline-borane product observed.

The reasons for this will be expanded in Chapter 2.28.

Lastly, a complex mixture of products was again observed for the bis(m-(CH3)) azobenzene

derivative 1g. Efforts were then focused upon independently synthesizing and characterizing the

R 1(%) 2 (%)* 3 (%)*

p-F (1b) 0 18 (2b) 82 (3b)

p-Cl (1c) 0 24 (2c) 76 (3c)

p-Br (1d) 0 17 (2d) 83 (3d)

p-tBu (1e) 0 34 (2e) 66 (3e)

p-iPr (1f) 0 18 (2f) 82 (3f)

m-CH3 (1g) 20 14** (2g) 43** (3g)

C6F5 (1h) N.R. - -

Table 2.2 Hydrogenations run at 100 atm. of hydrogen result in slightly better aniline-borane

ratios, with several exceptions. *All yields are reported by 1H NMR spectroscopy **A complex

mixture of products was observed for 1g, however the synthesis of 1g was confirmed by 1H NMR

spectroscopy and low resolution-mass spectrometry.

1 2 3

33

aniline-borane, 3g, that resulted from mixing bis(m-(CH3)) and B(C6F5)3 in 1:1 molar quantities.

Its corresponding spectra are reported as follows: peaks at 7.19-7.13 ppm, 7.13-7.07 ppm and

6.90-6.79 ppm in the 1H NMR spectrum in a 3:1:2 ratio reflected the aromatic and N-H proton

resonances of 3g. Also, peaks at -133.6 ppm, -156.9 ppm and -163.7 ppm in the 19

F NMR

spectrum reflected the C6F5 fluorine resonances of this species (meta-para gap ~ 6.9 ppm). A

sharp singlet peak at -5.7 ppm in the 11

B NMR spectrum indicated the presence of four-

coordinate boron. All of these peaks were consistent with our experimental hydrogenation data

confirming that the aniline-borane-adduct 3g had been synthesized. Also, this salt was observed

to constitute 43% of the product mixture. It should also be noted that peaks corresponding to the

hydrazine were inferred by 1H NMR, occurring as singlets at 2.10 ppm and 2.30 ppm, composing

14% of the product mixture. Additionally a peak of unknown identity at 1.64 ppm and present in

23% yield was observed. Lastly, 20% of the product mixture corresponded to unreacted 1g.

2.3.7 The Effect of a Sterically Encumbered Azobenzene Derivative on Hydrogenation

The effect that the tetrakis(o-iPr) sterically encumbered derivative of azobenzene, 1i, had on

hydrogenation was probed next. When this compound was subjected to identical hydrogenation

conditions as outlined in Chapter 2.26 only the starting material 1i was recovered (Scheme

2.1.9). When the temperature was increased to 60 °C and 1i was allowed to react for two days,

approximately 80% of the resultant product mixture corresponded to the hydrazine product 2i, by

1H NMR spectroscopy (Scheme 2.1.9). Its identity was also confirmed by mass spectrometry

(MS) and by 1H NMR spectroscopy, with a broad multiplet peak at 7.36-7.28 ppm and a broad

singlet at 4.81 ppm with a relative integration of 3:1 reflective of the aromatic C-H and N-H

34

resonances, respectively. Interestingly, 19

F NMR and 11

B NMR data support that a hydrazine-

borane complex had formed, with fluorine resonances at -136.2 ppm, -160.1 ppm and -165.4

ppm (meta-para gap ~ 5.3 ppm), while a boron resonance -3.8 ppm indicative of four-coordinate

boron

Scheme 2.1.9 Results of the hydrogenation trials with tetrakis(iPr) diazene derivative, 1i.

2.3.8 Mechanistic Insight into the Hydrogenation of Azobenzene

At this point it was possible to propose a likely mechanism of N=N hydrogenation based on our

data and literature precedent.8,76,71

The literature mechanism of the hydrogenation of imine 5

with the borenium FLP complex 4 was believed to be most similar (Scheme 2.2.0).8,76

In this

mechanism Stephan et. al, propose that activation of dihydrogen occurs from a borenium-imine

encounter complex to give the protonated iminium-borate salt 6 and borane 7.61

Addition of a

hydride from the borane 7 to the unsaturated carbon atom of the iminium cation 6 occurs next,

giving amine 8 and regenerating the borenium catalyst.

2i

1i

35

Scheme 2.2.0 Mechanism of FLP-catalyzed reduction of imines using a borenium cation-FLP

complex.

In contrast, the FLP-base in our system contained an N=N moiety that was reduced. It is

proposed that initial activation of dihydrogen occurs from the FLP encounter complex, 9, formed

between B(C6F5)3 and the azobenzene (Scheme 2.2.1). It should be noted that while no

quantitative evidence was collected with regard to the exact geometry of the azobenzene in the

FLP complex, azobenzenes are known to undergo facile interconversion between the (E) and (Z)

conformations. This may be a requirement in order to facilitate activation of H2.77-79

In any case,

activation of dihydrogen leads to the formation of the diazenium salt 10, analogous to salt 6 in

the proposed borenium mechanism (Scheme 2.21).

4

5

6

7

8

36

Scheme 2.2.1 Proposed mechanism of FLP-mediated hydrogenation of azobenzene to aniline.

Hydride transfer from the hydridoborate fragment of 10 to the monobasic nitrogen fragment then

follows to generate the hydrazine 12 and B(C6F5)3. Both these species have been verified

spectroscopically (See: Chapter 2.25). Subsequently, reduction of the remaining hydrazine

occurs via initial formation of a hydrazine-B(C6F5)3 encounter complex with H2, analogous to 9,

followed by hydride transfer from the resulting hydrazonium hydridoborate, analogous to 10, to

produce the aniline-borane salt 13 . It is as this point that B(C6F5)3 becomes quenched and unable

to facilitate further reduction chemistry, precluding its catalytic turnover of this system.

There also exists some mechanistic precedent with respect to the hydrogenation of azobenzenes

using similar systems. It was found that there was a large kinetic isotope effect (KIE) for the

hydride transfer step 11 when the azobenzene derivatives were reduced using the hydrogen

source ammonia-borane and a planar N-heterocyclic phosphane catalyst (See: Kinjo et. al.,

9

10

11

12

13

37

Scheme 2.1.0).60,80

In contrast, our system does not support such a rate-limiting step. This was

because at no point throughout our experiments was salt 10 observed. We observed that

increasing H2 pressures did not significantly improve conversion toward the aniline-borane

adduct, which suggests that protonation of the N-center, 10, as opposed to activation of of H2, 9,

was the slow step to hydrogenation (Scheme 2.2.1). To reiterate, the pKa of azobenzene was

~ 3.5, suggesting that loss of a proton following H2 activation was facile, further supports this

hypothesis.89

Additionally, we observed that formation of an amido-borane species was facile at

elevated temperatures when diphenylhydrazine and B(C6F5)3 were mixed (Schemes 2.1.4-2.1.5).

This implies, upon adduct formation between diphenylhyrdazine and B(C6F5)3, that the N-H

protons of diphenylhydrazine are sufficiently to affect cleavage of a C6F5 ring from B(C6F5)3

(Scheme 2.1.4). Therefore, it is likely that once addition of the first equivalent of H2 to the

diazene moiety occurred to produce hydrazine 12, that activation of a C6F5 ring of B(C6F5)3 by

the amine to produce an amido-borane was likely (see: Scheme 2.1.4). This may also explain

why while consumption of the hydrazine was never quantitative. This unwanted reactivity

precluded further reduction chemistry.

Also, hydrogen activation was never observed for derivative 1h regardless of the temperature,

time or hydrogen pressures used. We believe that this is due to the perfluoroarene rings

inductively withdrawing electron density from the nitrogen-center of 1h, resulting in insufficient

basicity for H2 activation. Also, no difference in yield was observed with the para-substituted

alkyl and halogen derivatives. This suggested that altering the electronics of the system slightly

through mono-substitution at the para position of the arene ring did not significantly alter

reactivity with H2. Slightly higher temperatures were required to hydrogenate the derivative 1i,

suggestive of a slight steric component to hydrogenation, although whether this effects formation

of the encounter complex or hydride transfer is unknown and will be investigated in future.

38

Lastly a mixture of at least three products was observed when the derivative 1g was subjected to

hydrogenation conditions, corresponding to the aniline-borane adduct, the hydrazine intermediate

as well as an unknown product. This suggested a steric effect caused lower conversion.

2.3.9 Hydrogenation of a Hydrazine Derivative of Diphenylamine: Results

In this work we focused upon oxidizing diphenylamine to its corresponding bulky 1,1,2,2-

tetraphenyhydrazine (TPH) analogue and probing its reactivity with B(C6F5)3 and dihydrogen,

with a specific emphasis on cleavage of the N-N bond. This would strengthen the above

mechanistic proposal which suggested that hydrogenation to the aniline proceeded via a

hydrazine intermediate. In addition, although aromatic hydrogenations of bulky amines and

B(C6F5)3 was well precedented within our group, they were never demonstrated in systems

containing an N-N bond. It was thus believed that TPH would be an optimal substrate to test this

reactivity.34,35,66,83

The synthesis of TPH was outlined previously by Tsuji and coworkers.84

To

our satisfaction, adding diphenylamine neat to an equivalent of pyridine and CuCl at room

temperature overnight, followed by aqueous work-up and recrystallization from hexanes resulted

in the clean formation of TPH (Scheme 2.2.2, yield: 65%).

Scheme 2.2.2 Cu(I) mediated synthesis of 1,1,2,2-Tetraphenylhydrazine.

39

This was confirmed by 1H NMR spectroscopy, which showed 3 broad multiplets at 7.28-7.34

ppm, 7.16-7.24 ppm and 6.87-6.93 ppm with relative integrations of 2:2:1, corresponding to the.

ortho, meta and para aromatic protons, respectively. Additionally, the absence of a broad singlet

peak at 5.70 ppm, which was present in the 1H NMR spectrum of diphenylamine (starting

material) confirmed that this oxidation protocol was successful. This was important as any

presence of amine could significantly influence the subsequent hydrogenation data.

Next, TPH and B(C6F5)3 were mixed in 1:1 molar quantities and their ability to form an FLP-

complex was examined spectroscopically. Only one broad singlet peak at ~ 55 ppm in the

corresponding 11

B NMR spectrum was observed, consistent with free B(C6F5)3. Additionally,

peaks at -127.3 ppm, -142.1 ppm and -159.3 ppm, reflective of the ortho-C6F5, para-C6F5 and

meta-C6F5, were also consistent with B(C6F5)3. Combined, these data told us that TPH formed a

non-interacting FLP-pair. Subsequently, a 2:1 solution of this hydrazine with B(C6F5)3 in

bromobenzene-d5 was prepared and subjected to 4 atm. of hydrogen. The reaction course was

monitored by 1H MMR,

11B NMR, and

19F NMR spectroscopy at 110 °C for a period of five

days (Scheme 2.2.3).

40

Scheme 2.2.3 Hydrogenation results of TPH at elevated temperatures and at one day intervals.

Relative ratios of products were determined by 1H NMR spectroscopy.

After only one day there were several prominent species present in solution by 1H NMR

spectroscopy, although their relative yields could not be determined. Diphenylamine, which gave

rise to a broad singlet at ~5.70 ppm (15), and C6F5H (16), appearing as a complex multiplet at ~

6.32 ppm (Scheme 2.2.3). These values were consistent with their literature shifts.73

Also partial

reduction of the arene ring was observed, typified by the presence multiplet peaks at 2.81-2.64

ppm (N-Cy), 1.33-1.15 ppm (Cy), 0.90-1.14 ppm (Cy) and 0.90-0.67 ppm (Cy) in the 1H NMR

spectrum (Scheme 2.2.3). However under these conditions and after one day, the fully reduced

product dicyclohexylammonium hydridoborate 14 was not observed. By the second day, this

Time

2 d

1 d

3 d

4 d

5 d

14

14 15 16 17

I5

16

41

product did appear as a broad singlet at ~ 4.47 ppm in the 1H NMR spectrum, characteristic of its

N-H proton resonances, but these peaks disappeared by the fifth day of monitoring, indicative

that this product had decomposed.

Also, after three days three major boron species were observed in the 11

B NMR spectrum: a four

coordinate boron at ~-3.46 ppm, characteristic of an adduct between diphenylamine and B(C6F5)3

(15); a doublet peak at ~ -23.7 ppm with a coupling constant of 79 Hz (1JB-H), consistent with

hydridoborate34

; as well as a three-coordinate borane at ~35 ppm, which, along with the

identification of C6F5H, proves the formation of an amino-borane (17). Note that the 19

F NMR

data are also consistent with the known resonances for C6F5H and the amino-borane 17.35

In fact,

after five days this amino-borane product was the only boron species observed by 11

B NMR

spectroscopy. This, combined with the fact that the amine protons corresponding to 14 were not

observed, indicated that 17 most likely corresponded to the dicyclohexylamido borane adduct.

Further characterization will be carried out in future. The formation of the amino-borane product

17 is likely a result of the high temperature.

In order to avoid formation of amino-borane 17, a 2:1 mixture of B(C6F5)3 and TPH was

prepared and subjected to 4 atm. of hydrogen in bromobenzene-d5 at a lower temperature than

our previous experiment (65 °C). Reaction progress and 1H NMR yields of each product were

then monitored over a period of two, six and twelve days. Quantitative consumption of TPH was

observed by 1H NMR spectroscopy after six days, with 14 and 15 composing 35% and 25% of

the product mixture, respectively. The remainder of the product mixture (40%) consisted of

partially reduced aromatic product(s). After twelve days under the reaction conditions,

conversion to salt 14 only increased marginally to 59%. Therefore lowering the temperature

allowed us to observe complete consumption of TPH after six days, while conversion toward 14

42

could not be improved despite increasing reaction times. The identity of 14 was found to be

spectroscopically and crystallographically consistent with the literature data for

dicycloxehylammonum hydridoborate (Figure 2.2 and see Chapter S8).34

Figure 2.2 POV-ray depiction of 14.

2.3.10 Hydrogenation of a Hydrazine Derivative of Diphenylamine: Discussion

Work by Stephan et. al. proposed a likely mechanism of aromatic hydrogenation from

diphenylamine. 34

In this mechanism, the diphenylammonium hydridoborate salt (Scheme 2.2.4,

18) can lose dihydrogen to generate diphenylamine (Scheme 2.2.4, 15).34

Our data were

consistent with this, as diphenylamine (15) was observed throughout the course of the reaction

(Scheme 2.2.4). Note this also implies that cleavage of the N-N bond of TPH occurred in our

system. This mechanism then goes on to propose that activation of dihydrogen occurs from the

B1

N1

43

resonance isomer of diphenylamine, 19, giving a 1,3-cyclohexadiene intermediate 20 (Scheme

2.2.4).34

Iteration of this mechanism result in the fully reduced species 14.This was also observed

throughout our hydrogenation runs of TPH. Our data was inconclusive in determining an order if

N-N bond cleavage occurred before, during or after arene hydrogenation. This could not be

clarified further even at temperatures as low as 65 °C. Lower temperature experiments are

recommended in the future in order to further elucidate this mechanism.

Scheme 2.2.4 Proposed mechanism of aromatic hydrogenation of diphenylamine by Stephan et.

al.34

2.3.11 Reactivity of an N-N Bond-Containing Compound not derived from Aniline: Results and Discussion

We wanted to expand the scope of our protocol to include diverse systems containing the N-N

moiety other than aniline. Phthalazine is an example of such a compound, and in addition to the

N-N bond it is characterized by a fused planar aromatic system (21, Scheme 2.2.5). It would be

interesting to investigate if such a system could form a viable FLP complex and if hydrogen

activation could be observed. Gratifyingly, mixing an equimolar solution of phthalazine with

B(C6F5)3 resulted in no adduct formation at room temperature, with 19

F NMR and 11

B NMR

18 15 19 14 20

44

peaks consistent with B(C6F5)3. This is likely a result of the electronic quenching of the lone-pair

of nitrogen about the aromatic system.

When we exposed phthalazine to 100 atm. of dihydrogen at 40 °C for 2 days in CH2Cl2,

complete reduction of the imine moieties was observed. This was confirmed by 1H NMR

spectroscopy showing a 1:1 relationship between the aromatic and methylene protons (Scheme

2.2.5). This spectrum also revealed a broad singlet at 6.78 ppm corresponding to an amine N-H

group with a relative integration of 1. Also observed was a complex multiplet at ~ 6.97 ppm,

consistent with C6F5H. The 11

B NMR spectrum of this species shows two major boron

resonances at 40.7 ppm and -4.7 ppm, indicative of boron in a three- and four-coordinate

environment, respectively (Scheme 2.2.5). This suggested, under our hydrogenation conditions,

that phthalazine gave rise to the amino-borane species 22 which contained two four-coordinate

boron species. This product, however, was not spectroscopically observed. This led us to

conclude that the amine of 22 was sufficiently protic to affect activation of a C6F5 ring of the

adjacent B(C6F5)3, forming the three-coordinate boron species 23 and C6F5H. The identity of

both of these species was confirmed by 1H NMR spectroscopy. This also explains why the

integration of the amine proton was 1.

45

Scheme 2.2.5 Hydrogenation of phthalazine. * Denotes Ar-H resonances, X Denotes CH2

resonances, O Denotes N-H resonances.

The 19

F NMR spectrum expanded these data, showing 25 total fluorine atoms with an unusual

splitting pattern. Sharp peaks, for example, at -126.7 ppm, -127.7 ppm, -139.6 ppm and -142.4

ppm were indicative of the o-B(C6F5)2 fluorine atoms, while peaks at -128.2 ppm and -131.9

ppm reflected the o-B(C6F5)3 fluorine atoms with a total relative integration of 1:1:2:4:1:1,

respectively (Scheme 2.2.5). Note that the inequivalence of the o-B(C6F5)2 fluorine atoms was

suggestive of inhibited rotation about the N-B bond. The m-B(C6F5)2 fluorine atoms appeared at -

22 23

1H NMR

19F NMR 11

B NMR

* *

o

x

x

x

* *

* *

x

x

o

ortho ortho

ortho

ortho

para

para

meta

meta

21 24

para

46

162.9 ppm and -163.7 ppm with a total relative integration of 1:1, while the p-B(C6F5)2 fluorine

atoms occurred at -157.1 ppm. Also, the meta-para fluorine gaps of 23 and 24 were ~ 13 ppm

and ~ 15 ppm. Therefore, this slight reduction, in addition to the inequivalence of the o-B(C6F5)2

fluorine atoms, reflected an absence of rotation about the N-B bond. This is due to resonance de-

localization of the amine lone-pair from 23 into the empty p-orbitals of the adjacent borane

forming 24. This species was confirmed by 19

F NMR and 11

B NMR spectroscopy (Scheme

2.2.5). Furthermore, our spectral data are consistent with previous literature reports of salts

similar to 24.84.85

All of these data, combined with the presence of C6F5H and low-resolution mass spectrometry

lead us to conclude that zwitterionic phthalazine 23 had been formed, which underwent

resonance delocalization forming the resonance isomer 24. It is interesting to note that such

selective reductions of imines in aromatic systems in the presence of N-N moieties are

unprecedented. Reduction of the hydrazine, moiety, was therefore precluded due to the nitrogen

in the amine-linked derivative being too acidic such that it decomposes the Lewis acid.

47

2.4 Conclusions

In conclusion, we now understand that hydrogen activation using FLPs containing azobenzene

bases is facile provided the appropriate temperatures and H2 pressures are used. Insight was

gained through synthesizing a library of azobenzene compounds of varying basicity and steric

bulk and subjecting them to varying hydrogenation conditions. In systems where the basicity of

the nitrogen center is inductively lowered, such as bis(pentafluorobenzene)azobenzene, 1h, no

reactivity with hydrogen was observed. Altering the electronics of the system slightly through

mono-substitution at the para position of the arene ring, however, did not significantly alter

reactivity of this FLP with H2. In the hydrogenation of TPH, we were able to show that cleavage

of the N-N bond and reduction of the aromatic system had occurred, although no order of

reactivity could be established. This system was also found to be sensitive to temperature, with

higher temperatures favouring formation of the amino-borane complex, while lower temperatures

favoured reduction to the dicyclohexylammonium hydridoborate salt. Also, reduction of the

aromatic N-N bond in phthalazine was not observed with our hydrogenation protocol due to the

acidity of the amino-borane adduct affecting decomposition of the borane. Eventually, these

protocols could be further developed to reduce stronger N-N bonds such as those in di-nitrogen

or di-nitrogen supported organometallic complexes.

48

2.5 Future Directions

There exists some precedent with respect to the synthesis of nitrogen-containing heterocycles

using N-based FLP systems. Work by our group has shown that intramolecular cyclizations of

N,N-dimethylaniline derivatives, substituted at the ortho position with olefin or acetylene

fragments, can be achieved using B(C6F5)3 (Scheme 2.2.6).14,50

The reaction proceeds through a

π-type interaction between the olefinic or acetylenic fragment and B(C6F5)3, followed by

intramolecular attack by the amine. Additionally, it was proposed that this reaction occurred due

to formation of the classical Lewis acid-base adduct being sterically precluded.50

Also, this

protocol is limited in its scope as it only results in the formation of five- and six-membered N-

containing heterocycles (Scheme 2.2.6).

Scheme 2.2.6 The synthesis of N-heterocycles via FLP-mediated intramolecular cyclization.

49

Subsequent work should attempt to expand the scope of FLP-mediated intramolecular

cyclizations to compounds containing the N=N moiety. Some interesting synthetic include the

cinnolines and cinnolinium salts (Figure 2.3). These compounds are known to have potent

anticancer, antimicrobial, and anti-inflammatory abilities as well as unusual optical and

luminescent characteristics. They are thus compounds of high pharmaceutical and synthetic

interest.40,41

The cinnolines and their derivatives have traditionally been accessed from metal-

catalyzed couplings of the corresponding hydrazines with aryl alkenes, with C-H activation being

a critical step.42-45

Figure 2.3. Various cinnolines and cinnolinium salts and their pharmaceutical/industrial

applications.

50

We envision that if a bulky enough diazene-containing precursor was reacted in the presence of

B(C6F5)3, the classical Lewis acid-base adduct would not be observed. This may facilitate an

intramolecular cyclization, allowing facile access to a cinnolinium precursor (Scheme 2.2.7).

Scheme 2.2.7 Cinnolines can be accessed from a diazene-anchored aromatic alkyne.

51

Studies into the Reactivity of Frustrated Lewis Pairs

Containing N-N Bases with Hydrogen

Daniel A. Dalessandro* and Douglas W. Stephan

Department of Chemistry, University of Toronto, 80 St. George Street,

Toronto, ON, M5S 3H, Canada

S0. Supporting Information

General Information S1.

All hydrogenations were carried out under an anhydrous N2 atmosphere using standard Schlenk

and glovebox techniques. All glassware was oven-dried and cooled under vacuum before use. All

diazenes/diazo compounds were prepared as previously recorded. Tetraphenylhydrazine was also

prepared according to previously reported protocols. All solvents were purchased from Fischer

Scientific and directly from the original bottle without further purification or drying, unless

otherwise specified. Commercial reagents were purchased from Sigma Aldrich, TCI or Apollo

Scientific and used without further purification unless indicated otherwise. CD2Cl2 (Aldrich) was

deoxygenated, distilled over CaH2, then stored over 4 Å molecular sieves before use. Molecular

sieves were activated by storage overnight in an oven at 120 oC. C6D5Br (Aldrich) was

deoxygenated and stored over 4 Å molecular sieves before use. All solid substrates were dried in

vacuo and stored in an inert atmosphere glovebox. Tris(pentafluorophenyl)borane was purchased

from Boulder Scientific and used without further purification. Hydrogen gas (Grade 5.0) was

obtained from Linde and purified through a Matheson Model 450B or Matheson Nanochem

WeldAssureTM

gas purifier.

52

All reactions were monitored using a Bruker Ultrashield 400 MHz,Bruker Advance III 400 MHz

NMR or Varian Mercury 300 MHz spectrometer. Chemical shifts are expressed in ppm values,

and 1H NMR are referenced to 0.00 ppm for Me4Si (TMS) and

13C NMR spectra are referenced

to 54.24 ppm for CD2Cl2. Peak multiplicities are designated by the following abbreviations: s,

singlet; br.s, broad singled; d, doublet; t, triplet; q, quartet; dq, doublet of quartets; m, multiplet;

J, coupling constant in Hz. Mass spectra were obtained by the University of Toronto Mass

Spectral Facility (AIMS); high-resolution mass spectra (HR-MS) were recorded on an AEI

MS3074 or AB/Sciex QStar mass spectrometer with an ESI source. Flash column

chromatography on silica gel (60 Å, 230-400 mesh, obtained from Silicycle Inc.) was performed

with reagent-grade chloroform and dichloromethane as eluent. As a method of comparison, all

final aniline compounds were synthesized independently, and compared to the experimentally

hydrogenated diazenes using the 1H,

19F and

11B nulcei.

General Procedures for NMR-Scale Hydrogenations S2.

A clean, dry J. Young tube was washed with water and acetone then stored in a 120 °C oven

overnight to dry. The tube was then left to cool overnight under vacuum and transferred into a

drybox. At this point, the tube was charged with the starting diazene and tris(pentafluorophenyl)

borane in CD2Cl2, unless otherwise specified, in a 1:2 equivalence ratio. The tube was sealed and

then subjected to three freeze-pump-thaw cycles. The tube was then frozen, evacuated and then

backfilled with hydrogen gas. The tube was then thawed and hydrogen activation products were

observed by 1H,

11B and

19F NMR spectroscopy at various intervals at 40 °C or 110 °C,

depending on the experiment.

53

General Procedures for Bomb-Scale Hydrogenations S3.

A clean, dry round-bottomed Schlenk flask was washed with water and acetone then stored in a

120 °C oven overnight to dry. The flask was then left to cool overnight under vacuum and

transferred into a drybox. At this point, the flask was charged with a stirring rod, the starting

diazene and tris(pentafluorophenyl) borane in CH2Cl2, unless otherwise specified, in a 1:2

equivalence ratio. The flask was sealed and then subjected to three freeze-pump-thaw cycles. The

flask was then frozen, evacuated and then backfilled with hydrogen gas to a pressure of

approximately 4 atmosphered. The resultant mixture was then allowed to stir at 40 °C for 48

hours. After this period, the mixture was concentrated in vacuo and dissolved in a minimal

amount of dichloromethane. The mixture was then purified through flash column

chromatography on a short pipette column (eluent: 10:1 dichloromethane:hexanes).

General Procedures for Parr®-Facilitated Hydrogenations S4.

In an inert atmosphere glovebox, the starting diazene (1 equiv.) and

tris(pentafluorophenyl)borane (2 equiv.) were weighed into separate vials.

tris(pentafluorophenyl)borane was then dissolved with approximately 2 mL of CH2Cl2. This

solution was then transferred into the vial containing the starting diazene. This vial was then

equipped with a stir bar and placed in a Parr pressure reactor. The rector was then sealed,

removed from the glovebox and attached to a thoroughly purged hydrogen gas line. The reactor

was purged 7 times at 50 atm with hydrogen gas and then 7 times at 102 atm. The reactor was

54

then sealed under 102 atm hydrogen gas and placed on a stir place overnight at 40 °C. The

reactor was slowly vented and an NMR sample was taken in CD2Cl2 following silica gel flash

chromatography on a short pipette column (eluent: dichloromethane). Conversion of the

unsaturated substrate to the aniline-derivative product was determined by 1H NMR spectroscopy.

Preparation of Azobenzene Starting Materials S5.

The parent diazene 1,2-diphenyldiazene (azobenzene) and hydrazine, 1,2-diphenylhydrazine

(hydrazobenzene) were purchased directly from TCI America and Sigma Aldrich, respectively,

and used unless otherwise specified without any further purification. All other diazenes were

synthesized according to known literature protocols unless otherwise specified.72,84

In general: A

50 mL round-bottomed flask equipped with a stirring bar was charged with CuBr (0.09 mmol,

12.9 mg, 0.03 equiv) and pyridine (0.27 mmol, 21.36 mg, 0.09 equiv) in 2 mL of toluene each.

Then, the desired aniline (3 mmol, 1 equiv.) in 6 mL of toluene was added to the same flask and

the mixture was stirred at room temperature for 5 minutes to allow for complete dissolution of

starting materials. A reflux condenser was then attached to the flask and the resultant mixture

was heated to 60 °C for 24 hours.

After this period, the mixture was concentrated in vacuo and dissolved in a minimal amount of

dichloromethane. The resultant mixture was purified via flash column chromatography on a

60mL fine ground-glass frit (eluent: 10:1 chloroform:hexanes, volume: 100 mL). The resultant

liquid was then concentrated in vacuo, and left under vacuum for 24 h to dry. It was found that

the starting material was of a sufficient amount of purity/dryness to use in subsequent

hydrogenations and was thus subjected to no further purification. All diazenes, unless otherwise

55

specified, were consistent wither previously reported literature compounds. (E)-1-phenyl-2-(p-

tolyl)diazene was purchased from Sigma Aldrich and used directly without further purification.

Preparation of 1,1,2,2-Tetraphenylhydrazine S6.

A 250 mL was equipped with a magnetic stir bar and charged with CuCl (20 mmol, 1.98g, 2

equiv.) in 50 mL of pyridine and stirred vigorously for 10 minutes until a consistent green slurry

was formed. Next, diphenylamine (9.99 mmol, 1.69 g, 1 equiv.) was dissolved in approximately

30 mL of pyridine in an Erlenmeyer flask and transferred into a 100 mL dropping funnel. The

diphenylamine was then added at room temperature dropwise (approximately at a rate of 1

drop/10 seconds) to the green slurry overnight. Following this period, the solution was

concentrated in vacuo and the resulting brown residue was dissolved in a minimal amount of

dichloromethane and was purified via flash column chromatography on a5 mL 60mL fine

ground-glass frit (eluent: 1:1 hexanes:toluene, 100 mL, then dichloromethane, 50 mL and

methanol, 5 mL). The resultant mixture was then concentrated in vacuo; to remove residual

pyridine from the sample the mixture was dissolved into a minimal amount of hexanes at room

temperature and sonicated. The insoluble residue was collected on a Büchner frit and washed 3X

with 10 mL of cold hexanes. NMR of the crude product showed no presence of free amine

starting material, indicating unsaturation at the nitrogen center.

56

NMR Data of Azobenzenes S7.

1H NMR (CDCl3, 400 MHz, δ): 7.89-7.97 (4H, m), 7.15-7.24 (4H, m);

19F NMR (CDCl3, 400

MHz, δ): -111.73 (1F, s) (Yield: 65%).

1H NMR

57

1H NMR (CDCl3, 400 MHz, δ): 7.81-7.86 (4H, m), 7.43-7.49 (4H, m) (Yield: 75%).

1H NMR

58

1H NMR (CDCl3, 400 MHz, δ): 7.73-7.79 (4H, m), 7.59-7.66 (4H, m) (Yield: 70%).

1H NMR

59

1H NMR (CDCl3, 400 MHz, δ): 7.81-7.86 (4H, m), 7.39-7.33 (4H, m), 2.99 (2H, sept.) 1.30

(12H, d) (Yield: 70%).

1H NMR

60

1H NMR (CDCl3, 400 MHz, δ): 7.87-7.93 (4H, m), 7.54-7.59 (4H, m), 1.41 (18H, s) (Yield:

70%).

1H NMR

61

1H NMR (CDCl3, 400 MHz, δ): 7.75-7.80 (4H, m), 7.40-7.46 (2H, m), 7.29-7.34 (2H, m), 2.49

(6H, s) (Yield: 70%).

1H NMR

62

1H NMR (CDCl3, 400 MHz, δ): 7.28-7.36 (6H, m), 3.26 (4H, sept.) 1.20 (24H, d,

1J = 18.4 Hz)

(Yield: 75%).

1H NMR

63

19F NMR (CDCl3, 400 MHz, δ): -132.05 (m, 6F), -135.13 (m, 4F) (Yield: 30%).

1H NMR

64

19F NMR

65

1H NMR (CDCl3, 400 MHz, δ): 7.28-7.34 (8H, m), 7.16-7.24 (8H, m) 6.87-6.93 (4H, m) (Yield:

65%).

1H NMR

66

Hydrogenation Results S8.

1H NMR (C6D6, 400 MHz, δ): 6.50-6.60 (3H, m), 6.29-6.37 (2H, m) 5.81 (2H, br.s)

19F NMR

(C6D6, 400 MHz, δ): -133.2 (2F, br, o-C6F5), -154.9 (1F, br, p-C6F5), -162.5 (2F, br, m-C6F5). 11

B

NMR (C6D6, 400 MHz, δ): -5.89 (s, H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz, δ): 148.3 (dm,

1JC-F ~ 239 Hz, CF), 140.8 (dm,

1JC-F ~ 253 Hz, CF), 137.8 (dm,

1JC-F ~ 247 Hz), 130.5 (p-Ph),

1H NMR

67

129.6 (m-Ph), 123.0 (o-Ph). MS (Dart Ionization), [m/z, (%)]: 604.0 ([M-H]-), HRMS (Dart

Ionization, m/z) calcd. For C24H7BF15N, [M-H]-: 604.034; found: 604.0369. (Yield: 95%).

1H NMR

19F NMR

68

1H NMR (C6D6, 400 MHz, δ): 6.47-6.64 (3H, m), 6.26-6.42 (2H, m) 5.72-5.90 (2H, br.s)

19F

NMR (C6D6, 400 MHz, δ): -132.9 (2F, br, o-C6F5), -154.7 (1F, br, p-C6F5), -162.3 (2F, br, m-

C6F5). 11

B NMR (C6D6, 400 MHz, δ): -5.60 (s, H2NB(C6F5)3) (Yield: 85%). Due to match in

NMR data to previously reported compound, no further spectral data was collected.

11B NMR

69

1H NMR

19F NMR

70

1H NMR (CD2Cl2, 400 MHz, δ): 6.95-7.11 (4H, m), 6.89 (2H, s).

19F NMR (CD2Cl2, 400 MHz,

δ): -111.7 (1F, br, C5H4F), -133.7 (6F, br, o-C6F5), -156.0 (3F, br, p-C6F5), -163.1 (6F, br, m-

C6F5). 11

B NMR (CD2Cl2, 400 MHz, δ): -5.49 (s, H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz,

δ): 148.2 (dm, 1JC-F ~ 239 Hz, CF), 140.8 (dm,

1JC-F ~ 249 Hz, CF), 137.7 (dm,

1JC-F ~ 252 Hz),

130.5 (m-Ph), 129.6 (CNH2), 123.0 (o-Ph), 116.7 (CF). MS (Dart Ionization), [m/z, (%)]: 622.0

([M-H]-), HRMS (Dart Ionization, m/z) calcd. For C24H6BF16N, [M-H]

-: 622.0272; found:

622.0269. (Relative yield: 82%).

11B NMR

71

1H NMR

19F NMR

72

11B NMR

13C NMR

73

1H NMR (CD2Cl2, 400 MHz, δ): 7.25-7.30 (2H, m), 6.99-7.04 (2H, m), 6.90 (2H, br.s).

19F

NMR (CD2Cl2, 400 MHz, δ): -133.7 (2F, br, o-C6F5), -155.9 (1F, br, p-C6F5), -163.0 (2F, br, m-

C6F5). 11

B NMR (CD2Cl2, 400 MHz, δ): -5.33 (s, H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz,

δ): 148.4 (dm, 1JC-F ~ 239 Hz, CF), 140.8 (dm,

1JC-F ~ 249 Hz, CF), 137.8 (dm,

1JC-F ~ 251 Hz),

132.3 (CNH2), 128.3 (m-Ph), 122.6 (o-Ph), 116.7 (CCl). MS (Dart Ionization), [m/z, (%)]:

637.997 ([M-H]-), HRMS (Dart Ionization, m/z) calcd. For C24H6BClF15N, [M-H]

-: 637.9974;

found: 637.9974. (Relative yield: 76%).

1H NMR

74

11B NMR

19F NMR

75

1H NMR (CD2Cl2, 400 MHz, δ): 7.41-7.46 (2H, m), 6.92-6.98 (2H, m), 6.85-6.92 (2H, br.s).

19F

NMR (CD2Cl2, 400 MHz, δ): -133.7 (2F, br, o-C6F5), -155.9 (1F, br, p-C6F5), -163.0 (2F, br, m-

C6F5). 11

B NMR (CD2Cl2, 400 MHz, δ): -5.55 (s, H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz,

δ): 148.3 (dm, 1JC-F ~ 239 Hz, CF), 141.0 (dm,

1JC-F ~ 249 Hz, CF), 137.8 (dm,

1JC-F ~ 251 Hz),

133.7 (CNH2), 133.6 (m-Ph), 124.8 (o-Ph), 123.5 (CBr). MS (Dart Ionization), [m/z, (%)]: 172.0

([M-B(C6F5)3]-) (Relative yield: 83%).

13C NMR

76

1H NMR

19F NMR

77

11B NMR

13C NMR

78

1H NMR (CD2Cl2, 400 MHz, δ): 7.10-7.15 (2H, m), 6.92-6.98 (2H, m), 6.83 (2H, br.s), 2.83

(1H, sept.), 1.13-1.16 (6H, m). 19

F NMR (CD2Cl2, 400 MHz, δ): -133.5 (2F, br, o-C6F5), -156.8

(1F, br, p-C6F5), -163.6 (2F, br, m-C6F5). 11

B NMR (CD2Cl2, 400 MHz, δ): -5.59 (s,

H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz, δ): 148.3 (dm, 1JC-F ~ 244 Hz, CF), 140.8 (dm,

1JC-F ~ 251 Hz, CF), 137.7 (dm,

1JC-F ~ 251 Hz), 132.4. (p-Ph), 128.3 (CNH2), 122.0 (m-Ph),

116.7 (o-Ph), 34.2 (C(CH3)2), 23.9 (CCH3)2. MS (Dart Ionization), [m/z, (%)]: 646.08 ([M-H]-)

(Relative yield: 82%).

1H NMR

79

19F NMR

11B NMR

80

1H NMR (CD2Cl2, 400 MHz, δ): 7.25-7.31 (2H, m), 6.91-6.98 (2H, m), 6.83 (2H, br.s), 1.22

(9H, s). 19

F NMR (CD2Cl2, 400 MHz, δ): -133.5 (2F, br, o-C6F5), -156.8 (1F, br, p-C6F5), -163.5

(2F, br, m-C6F5). 11

B NMR (CD2Cl2, 400 MHz, δ): -5.87 (s, H2NB(C6F5)3). 13

C NMR (CD2Cl2,

400 MHz, δ): 148.3 (dm, 1JC-F ~ 239 Hz, CF), 140.7 (dm,

1JC-F ~ 249 Hz, CF), 137.6 (dm,

1JC-F ~

251 Hz), 132.0 (p-Ph), 127.2 (CNH2), 122.5 (m-Ph), 116.1 (o-Ph), 31.6 (C(CH3)3, 31.2

(C(CH3)3. MS (Dart Ionization), [m/z, (%)]: 661.21 ([M-H]-) HRMS (Dart Ionization, m/z)

13C NMR

81

calcd. For C28H15BF15N, [M-H]-: 660.0989; found: 660.0090. (Yield: 95%). (Realtive yield:

66%).

1H NMR

82

11B NMR

19F NMR

83

**Note: Due to the sample consisting of ~50% of the desired anilinium salt by NMR, as a

mixture with the starting diazene and hydrazine intermediate, proper peak integration

could not be conducted on the parent spectrum. As a result, the compound was synthesized

independently through mixing of the desired aniline with tris(pentafluorophenyl)borane to

form the anilinium salt. The compound was then characterized fully and the peaks

corresponding to this compound are reported herein. All spectral data between the

13C NMR

84

hydrogenation product are consistent with the independently synthesized compound.

Additionally, mass spectral data of the hydrogenation product confirm its synthesis.

1H NMR (CD2Cl2, 400 MHz, δ): 7.14-7.20 (3H, m), 7.09-7.12 (1H, m), 6.95 (2H, br.s), 6.85-

6.89 (1H, m), 6.80-6.85 (1H, m) . 19

F NMR (CD2Cl2, 400 MHz, δ): -133.6 (2F, br, o-C6F5), -

156.9 (1F, br, p-C6F5), -163.7 (2F, br, m-C6F5). 11

B NMR (CD2Cl2, 400 MHz, δ): -5.65 (s,

H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz, δ): 148.3 (dm, 1JC-F ~ 245 Hz, CF), 141.2 (dm,

1JC-F ~ 249 Hz, CF), 137.8 (dm,

1JC-F ~ 249 Hz), 141.1 (CNH2), 134.8 (CCH3), 130.2 (Ph), 123.6

(Ph), 119.9 (Ph) . MS (Dart Ionization), [m/z, (%)]: 618.05 ([M-H]-) HRMS (Dart Ionization,

m/z) calcd. For C25H9BF15N, [M-H]-: 618.0520; found: 618.0520. (Relative yield: 43%).

1H NMR

85

1H NMR

19F NMR

19F NMR

86

11B NMR

13C NMR

87

**Note That the compound was synthesized following literature procedures outlined by

Mahdi et. al, 2012. All spectroscopic peaks reported below are consistent with

aforementioned literature reports. Additionally, a molecular structure of the above

compound was also obtained via single-crystal X-Ray diffraction.

1H NMR (C6D5Br, 400 MHz, δ): 4.47 (br. s, 2H, NH2), 2.97-3.08 (m, 1H, BH), 2.64-2.81 (m,

2H, N-Cy), 1.15-1.33 (m, 4H, Cy), 0.90-1.14 (m, 4H, Cy), 0.67-0.90 (m, 12H, Cy). 19

F NMR

(C6D5Br, 400 MHz, δ): -133.1 (2F, br, o-C6F5), -160.7 (1F, br, p-C6F5), -164.6 (2F, br, m-C6F5).

11B NMR (C6D5Br, 400 MHz, δ): -23.7 (d, BH,

1JB-H ~ 90 Hz).

13C NMR (CD2Cl2, 400 MHz,

δ): 148.3 (dm, 1JC-F ~ 236 Hz, CF), 139.9 (dm,

1JC-F ~ 249 Hz, CF), 137.3 (dm,

1JC-F ~ 248 Hz),

88

123.9 (br, i-C6F5), 57.3 (N-Cy), 24.7 (Cy), 24.6 (Cy). MS (Dart Ionization), [m/z, (%)]: 182.2

([M-HB(C6F5)3]-) (Relative yield: 35%).

\

1H NMR

89

19F NMR

90

11B NMR

13C NMR

91

1H NMR (CD2Cl2, 400 MHz, δ): 7.28-7.36 (m, 6H, Ph), 4.81 (br. s, 2H, NH), 3.24 (sept, 4H,

CH(CH3)2), 1.20 (24H, d, CH(CH3)2, 3JH-H ~ 6.6 Hz).

19F NMR (CD2Cl2, 400 MHz, δ): -136.2

(2F, br, o-C6F5), -160.1 (1F, br, p-C6F5), -165.4 (2F, br, m-C6F5). 11

B NMR (CD2Cl2, 400 MHz,

δ): -3.76 (s, H2NB(C6F5)3). 13

C NMR (CD2Cl2, 400 MHz, δ): 148.5 (dm, 1JC-F ~ 236 Hz, CF),

139.9 (dm, 1JC-F ~ 249 Hz, CF), 137.4 (dm,

1JC-F ~ 248 Hz), ), 149.4 (C-NH2), 141.5 (o-Ph),

129.2 (p-Ph), 124.3 (m-Ph), 28.1 (C(CH3)2, 24.5 (C(CH3)2. MS (Dart Ionization), [m/z, (%)]:

353.3 ([M- B(C6F5)3]-) (Relative yield: 70%).

92

1H NMR

19F NMR

93

11B NMR

13C NMR

94

1H NMR (CD2Cl2, 400 MHz, δ): 7.28-7.35 (m, 2H, ArH), 7.09-7.22 (m, 2H, ArH), 6.78 (br. s, 1

H NHB(C6F5)3), 4.60-4.69 (m, 1H, CH2), 4.22-4.32 (m, 2H, CH2), 4.08-4.18 (m, 1H, CH2). 19

F

NMR (CD2Cl2, 400 MHz, δ): -126.7 (1F, br, B(o-C6F5)2), -127.7 (1F, br, B(o-C6F5)2), -128.2

(2F, br, B(o-C6F5)3, -131.9 (4F, br, B(o-C6F5)3), -139.6 (1F, br, B(o-C6F5)2), -142.4 (1F, br, B(o-

C6F5)2), -149.9 (2F, br, B(p-C6F5)2), -155.4 (1F, br, B(p-C6F5)3), -157.0 (2F, br, B(p-C6F5)3), -

161.8 (2F, br, B(m-C6F5)3), -162.2 (4F, br, B(m-C6F5)3), -162.9 (2F, br, B(m-C6F5)2), -163.7 (2F,

br, B(m-C6F5)2) .11

B NMR (CD2Cl2, 400 MHz, δ): 40.7 (br. s, NB(C6F5)2), -4.7 (s, NB(C6F5)3).

13C NMR (CD2Cl2, 400 MHz, δ): 148.6 (dm,

1JC-F ~ 245 Hz, CF), 143.5 (dm,

1JC-F ~ 255 Hz,

CF), 138.0 (dm, 1JC-F ~ 251 Hz), 130.2 (Ar), 129.1 (Ar), 128.5 (Ar), 128.2 (Ar), 127.3 (Ar), 127.0

(Ar), 51.6 (CH2NB(C6F5)3), 49.6 (CH2NB(C6F5)2). MS (Dart Ionization), [m/z, (%)]: 990.3

([M]), 991.3 ([M+H]-), 989.2 ([M-H]

-) (Relative yield: 95%).

95

1H NMR

19F NMR

96

11B NMR

13C NMR

97

References

(1) Lewis, G.N. Valence and the Structure of Atoms and Molecules; Chemical Catalogue

Company, Inc.: New York, 1923.

(2) IUPAC. Compendium of Chemical Terminology, 2nd ed. (the "Gold Book").

Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications,

Oxford (1997). XML on-line corrected version: http://goldbook.iupac.org (2006-)

created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins.

(3) March, J. Advanced Organic Chemistry, 4 Ed; J. Wiley and Sons.: New York, 1992.

(4) Brown, H.C.; Schlesinger, H.I.; Cardon, S.Z. J. Am. Chem. Soc. 1942, 64, 325.

(5) Wittig, G.; Benz, E.; Chem. Ber. 1959, 92, 1999.

(6) Roesler, R.; Piers, W.E.; Parves, M. J. Organomet. Chem. 2003, 680, 218.

(7) Tochtermann, W. Angew. Chem. Int. Ed. 1966, 5, 351.

(8) Stephan, D.W.; Erker, G. Angew. Chem. Int. Ed. 2010, 49, 46.

(9) Stephan, D.W. Org. Biomol. Chem. 2008, 6, 1535.

(10) Stephan, D.W. Dalton Trans. 2009, 3129.

(11) Welch, G.C.; Juan, R.R.S.; Masuda, J.D.; Stephan, D.W. Science. 2006, 314, 1124.

(12) Tokob, T.A.; Hamza, A.; Pápai, I. J. Am. Chem. Soc. 2009, 131, 10701.

(13) Welch, G.C.; Stephan, D.W. J. Am. Chem. Soc. 2007, 129, 1880.

(14) Neu, R.C.; Otten, E.; Lough, A.; Stephan, D.W. Chem. Sci. 2011, 2, 170.

(15) Jursic, B.S.; J. Mol. Struct. 1999, 492, 97.

(16) Moroz, A.; Sweany, R.L. Inorg. Chem. 1992, 31, 5236.

(17) Rokob, T.A.; Hamza, A.; Stirling, A.; Pápai. J. Am. Chem. Soc. 2009, 131, 2029.

98

(18) Privalov, T. Dalton Trans. 2009, 1321.

(19) Guo, Y.; Li, S. Inorg. Chem. 2008, 47, 6212.

(20) Mӧmming, C.M.; Otten, E.; Kehr, G.; Frӧlich, R.; Grimme, S.; Stephan, D.W.; Erker,

G. Angew Chem. Int. Ed. 2009, 48, 6643.

(21) Sajid, M,; Klose, A.; Birkmann, B.; Liang, L.; Schirmer, B.; Wiegand, T.; Eckert, H.;

Lough, A.J.; Frӧlich, R.; Daniliuc, C.G.; Grimme, S.; Stephan, D.W.; Kehr, G.; Erker,

G. Chem. Sci. 2013, 4, 213.

(22) Spies, P.; Schwendemann, S.; Lange, S.; Kehr, G.; Frӧlich, R.; Erker, G. Angew.

Chem. Int. Ed. 2008, 47, 7543.

(23) Mӧmming, C.M.; Frӧmel, S.; Kehr, G.; Frӧlich, R.; Grimme, S.; Erker, G. J. Am.

Chem. Soc. 2009, 131, 12280.

(24) McCahill, J.S.J.; Welch, G.C.; Stephan, D.W. Angew. Chem. Int. Ed. 2007, 46, 4968.

(25) Dureen, M.A.; Stephan, D.W. J. Am. Chem. Soc. 2009, 131, 8396.

(26) Ulrich, M.; Seto, K.S.H.; Lough, A.J.; Stephan, D.W. Chem. Commun. 2009, 2335.

(27) Wittig, G.; Ruckert, A. Justus Liebigs Ann. Chem. 1950, 566, 101.

(28) Breen, T.L.; Stephan, D.W. Inorg. Chem. 1992, 31, 4019.

(29) Welch, G.C.; Masuda, J.D.; Stephan, D.W.; Inorg. Chem. 2006, 45, 478.

(30) Sumerin, V.; Shulz, F.; Neger, M.; Leskelä, M.; Repo, T.; Rieger, B. Angew. Chem.

Int. Ed. 2008, 47, 6001

(31) Ashley, A.E.; Thompson, A.L.; O’Hare, D. Angew Chem. Int. Ed. 2009, 48, 9839.

(32) Voss, T.; Mahdi, T.; Otten, E.; Frӧlich, R.; Kehr, G.; Stephan, D.W.; Erker, G.E.

Organometallics, 2012, 31, 2367.

(33) Chase, P.A.; Jurca, T.; Stephan, D.W. Chem. Commun. 2008, 1701.

(34) Mahdi, T.; Heiden, Z.M.; Grimme, S.; Stephan, D.W. J. Am. Chem. Soc. 2012, 134,

4088.

99

(35) Mahdi, T.; del Castillo, J.N.; Stephan, D.W.; Organometallics. 2013, 32, 1971.

(36) Mahdi, T.; Stephan, D.W. Angew. Chem. Int. Ed. 2013, 52, 12418.

(37) Eller, C.; Kehr, G.; Daniliuc, C.G.; Frӧlich, R.; Erker, G. Organometallics. 2013, 32,

384.

(38) Yu, J.; Kehr, G.; Daniliuc, C.G.; Erker, G. Inorg. Chem. 2013, 52, 11661.

(39) Blanksby, S.J.; Ellison, G.B. Acc. Chem. Res. 2003, 36, 255.

(40) Lewgowd, A.; Stanczak, A. Arch. Pharm. Chem. Life Sci. 2007, 340, 65.

(41) Kenneford, J.R.; Lourie, E.M.; Morley, J.S.; Simpson, J.C.E.; Williamson, J.; Wright,

P.H. Nature, 1948, 161, 603.

(42) Ball, C.J.; Gilmore, J.; Willis, M.C. Angew. Chem. Int. Ed. 2012, 51, 5718.

(43) Zhang, G.; Miao, J.; Zhao, Y.; Ge, H. Angew. Chem. Int. Ed. 2012, 51, 8318.

(44) Kiselyov, A.S.; Dominguez, C. Tetrahedron Letters. 1999, 40, 5111.

(45) Zhao, D.; Wu, Q.; Huang, X.; Song, F.; Lv, T.; You, J. Chem. Eur. J. 2013, 19, 6239.

(46) Mӧmming, C.M.; Frӧmel, S.; Kehr, G.; Frӧlich, R.; Grimme, S.; Erker, G. J. Am.

Chem. Soc. 2009, 131, 12280.

(47) Sortais, J.-B.; Voss, T.; Kehr, G.; Frӧlich, R.; Erker, G. Chem. Commun. 2009, 7417.

(48) Fukazawa, A.; Yamada, H.; Yamaguchi, S. Angew. Chem. Int. Ed. 2008, 47, 5582.

(49) Kehr.; G.; Erker, G. Chem. Commun. 48, 1839.

(50) Voss, T.; Chen, C.; Kehr, G.; Nauha, E.; Erker, G.; Stephan, D.W. Chem. Eur. J. 2010,

16, 3005.

(51) Merino, E.; Ribagorda, M. J. Org. Chem. 2012, 8, 1071.

(52) Garcia-Amorós, J.; Valasco, D. J. Org. Chem. 2012, 8, 1003.

(53) Chen, D.; Klankermayer, J. Chem. Commun. 2008, 1701.

100

(54) Chen, D.; Want, Y.; Klankermayer, J. Angew. Chem. Int. Ed. 2010, 49, 9479.

(55) Eisch, J.J.; Gitua, J.N. Organometallics. 2003, 22, 24.

(56) Holzwarth, M.S.; Alt, I.; Plietker, B. Angew. Chem. Int. Ed. 2012, 51, 5551.

(57) Schabel, T.; Belger, C.; Plietker, B. Org. Lett. 2013, 15, 2858.

(58) Jagadeesh, R.V.; Wienhӧfer, G.; Westerhaus, F.A.; Surkus, A.-E.; Junge, H.; Junge,

K.; Beller, M. Chem. Eur. J. 2011, 17, 14375.

(59) Yu, X.H.; Ma, X.J.; Jin, S.P.; Zhen, Y.Z. Synth. Commun. 2014, 44 707.

(60) Chong, C.C.; Hirao, H.; Kinjo, R. Angew. Chem. Int. Ed. 2014, 53, 3342.

(61) Farrell, J.M.; Hatnean, J.A.; Stephan, D.W. J. Am. Chem. Soc. 2012, 134, 15728.

(62) Reddy, J.S.; Xu, B.; Mahdi, T.; Frӧlich, R.; Kehr, G.; Stephan, D.W.; Erker, G.

Organometallics. 2012, 31, 5638.

(63) Erӧs, G.; Mehdi, H.; Pápai, I.; Rokob, T.A.; Soós, T. Angew. Chem. Int. Ed. 2010, 49,

6559.

(64) Molina, C.L.; Chow, C.P.; Shea, K.J. J. Org. Chem. 2007, 72, 6816.

(65) Xiong, F.; Qian, C.; Lin, D.; Zeng, W.; Lu, X. Org. Lett. 2013, 15, 5444.

(66) Zhu, Y,; Shi, Y. Org. Lett. 2013, 15, 1942.

(67) Stephan, D.W. Org. Biomol. Chem. 2012, 10, 5740.

(68) Kehr, G.; Schwendermann, S.; Erker, G. In Frustrated Lewis Pairs: Uncovering and

Understanding; Erker, G,; Stephan, D.W., Eds.; Springer Heidelberg, 2013; Vol. 1; p

85.

(69) Ma, X.-T.; Tian, S.-K. Adv. Synth. Catal. 2013, 355, 337.

(70) Merino, E. Chem. Soc. Rev. 2011, 40, 3835.

(71) Baer, E.; Tosoni, A.L. J. Am. Chem. Soc. 1956, 78, 2857.

(72) Zhang, C.; Jiao, N. Angew. Chem. Int. Ed. 2010, 49, 6174.

101

(73) Chase, P.A.; Stephan, D.W. Angew. Chem. Int. Ed. 2008, 47, 7433.

(74) Holschumacher, D.; Bannenberg, T.; Hrib, C.G.; Jones, P.G.; Tamm, M. Angew.

Chem. Int. Ed. 2008, 47, 7428.

(75) Taft, R.W.; Lewis, I.C. J Am. Chem. Soc. 1958, 80, 2436.

(76) Rokob, T.-A.; Pápai, I. In Frustrated Lewis Pairs: Uncovering and Understanding;

Erker, G,; Stephan, D.W., Eds.; Springer Heidelberg, 2013; Vol. 1; p 157.

(77) Yager, K.G.; Barret, C.G. In Azobenzene Polymers as Photomechanical

Multifunctional Smart Materials. Shahinpoor, M.; Schneider, H.-J. Eds.; Cambridge:

Royal Society of Chemistry, 2008; p 426.

(78) Brown, E.V.; Granneman, R.G. J. Am. Chem. Soc. 1975, 97, 621.

(79) Quick, M.; Dobryakov, A.L.; Gerecke, M.; Richter, C.; Berndt, F.; Ioffe, I.N.;

Granovsky, A.A.; Mahrwald, R.; Ernsting, N.P.; Kovalenko, S.A. Journal of Physical

Chemistry B. 2014, 118, 8756.

(80) Yang, X.; Zhao, L.; Fox, T.; Wang, Z.-X.’ Berke, H. Angew. Chem. Int. Ed. 2010, 49,

2058.

(81) Yan, X.-M.; Chen, Z.-M.; Yang, F.; Huang, Z.-Z. Synlett. 2011, 4, 569.

(82) Zhang, L.; Xia, J.; Li, Q.; Li, X.; Wang, S. Organometallics. 2011, 30, 375.

(83) Kajimoto, T.; Takahashi, H.; Tsuji, J. Bull. Chem. Soc. Jpn. 1982, 55, 3673.

(84) Winkelhaus, D.; Vishnevskiy, Y.V.; Berger, R.J.F.; Stammler, H.-G.; Neumann, B.;

Mitzel, N.W. Z. Anorg. Allg. Chem. 2013, 639, 2086.

(85) Winkelhaus, D.; Stephan, D.W. Angew. Chem. Int. Ed. 2014, 126, 5518.

(86) March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th

ed.; John Wiley and Sons.: New York, 1992.

(87) Severio, A.D.; Focante, F.; Camurati, I,; Resconi, L.; Beringhelli, T.; D’Alfonso, G.;

Donghi, D.; Maggioni, D.; Mercandelli, P.; Sironi, A. Inorg. Chem. 2005, 44, 5030.

102

(88) Chase, P.A.; Stephan, D.W. Angew. Chem. Int. Ed. 2008, 47, 7433.

(89) Bordwell, F.G. Acc. Chem. Res. 1988, 21, 456.

(90) Chinchilla, R.; Nájera, Chem. Rev. 2013.

(91) March, J. Advanced Organic Chemistry: Reactions Mechanism and Structure, 3rd

ed.;

Wiley: New York, 1985.