I. Cleavage of tetrahydrofurans in n-butyllithium; II. Rotation … · 2020. 4. 2. · of n-butyllithium with various tetrahydrofurans0 A news high yield preparation of lithium enolates

I. Cleavage of tetrahydrofurans in n-butyllithium;II. Rotation barriers in pentadienyllithiums

Item Type text; Dissertation-Reproduction (electronic)

Authors Potter, Dale Eugene, 1943-

Publisher The University of Arizona.

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X0 CLEAVAGE OF TETRAHYDROFURMS IN n-BUTYLLlTHIUM

lie ROTATION BARRIERS IN PENTADIENYLLITHIUMS

Dale Eugene Potter

A Dissertation Submitted to the Faculty of the

DEPARTMENT OF CHEMISTRY

In Partial Fulfillment of the Requirements For the Degree of

DOCTOR OF PHILOSOPHY '

In the Graduate College

THE UNIVERSITY OF ARIZONA

1 9 6 9

THE UNIVERSITY OF ARIZONA

GRADUATE COLLEGE

I hereby recommend that this dissertation prepared under my

direction by Dale Eugene Potter___________________

entitled I. CLEAVAGE OF TETRAHYDROFURANS IN n-BUTYLLITHIUM

II. ROTATION BARRIERS IN PENTADIENYLLITHIUMS________

be accepted as fulfilling the dissertation requirement of the

degree of _______________ Doctor of Philosophy___________________

7.X3-61Dissertation Director Date

After inspection of the final copy of the dissertation, the

following members of the Final Examination Committee concur in

its approval and recommend its acceptance:*

0xx/61

This approval and acceptance is contingent on the candidate's adequate performance and defense of this dissertation at the final oral examination. The inclusion of this sheet bound into the library copy of the dissertation is evidence of satisfactory performance at the final examination.

STATEMENT BY AUTHOR

This dissertation has been submitted in partial fulfillment of requirements for an advanced degree at The University•of Arizona and is deposited in the University Library to be made available to borrowers under rules of the Library0

Brief quotations from this dissertation are allowable without ■special permission, provided that accurate acknowledgment of source is madeo Requests for permission for extended quotation from or reproduction of this manuscript in whole or in part may be granted by the head of the major department or the Dean of the Graduate College when in his judgment the proposed use of the material is in the interests of scholarshipc In all other instances, however, permission must be obtained from the author0

SIGNED:

TO MICHELE

ACKNOWLEDGMENTS

The author wishes to express his sincere thanks to Dr. Robert

B„ Bates for his assistance and advice during the course of this work

and to Mrs. J. L. Cude for the typing of the final manuscript.

Financial support for this research from an Ethyl Corporation

Fellowship for 1968-1969 is gratefully acknowledged.

TABLE OF CONTENTS

Page

LIST OF ILLUSTRATIONS vii ■

LIST OF TAB LES eo e e e e o e e o c c o o o G o o o e o o o o o 15C

ABSTRACT o © © © o o o o o o © o e © © © o c - © o ® < i © o o © © o X

PART Is CLEAVAGE OF TETRAHYDROFURANS IN’ n~BUTYLLITHIUM . . . . * 1

INTRODUCTION o o o o o o o e o o e o o o o e o e c o o c o © 2

• Stability of Organometallic Compounds in THF 0 © © ® « © ‘ 2Mechanisms of THF Cleavage Reactions. © © © © © © © © © © 6Solvation Effects of Substituted Tetrahydrofurans © © © © 7

EXPERIMENTAL 0 © © © © « © © © © © © © © © © « © © © © © © © 9

Reaction of THF With n-Butyllithium © © © © © © © » © © © 9Lithium Enolate 0 2THF 0 ©©©. © © © © © © © © © o © © © 10Hydrolysis of Lithium Enolate © © • © © © © © © © © © © © 10Tritiation of Tetrahydrofurany1 Anion 0 © © © © © © « © © 10Deuteration of Tetrahydrofurany1 Anion © © © © © © © © © 12Hydrolysis of Tetrahydrofurany1 Anion © © © © © © « © © « 123 9 4 ~ Dime thy 11 e t r ahy d r o f u r an « © * © * « © ' © © * ■ © « © © © 12Preparation of PentadienyHithium in VariousTetrahydrofurans . * « . © . . © . © * * © * © © © © . 13

DISCUSSION OF RESULTS 15

Preparation of Lithium Enolate « © © © © © « © © © © © © 15Mechanism for. Cleavage of Tetrahydrofuran © © © © © © © © 18a- Versus 0-Cleavage of Substituted Tetrahydrofurans © © 22Possible Mechanism for p-Cleavage » e « © . © » « © « © © « 24Solvation Effects in the Cleavage Reactions © © © © © © « 25Rotation Barriers in Lithium Enolates © . © © © . . © ©.© 29Conclusions © © © © © @ © © © * © *.©*©©.© © © ©© © © 33

PART II: ROTATION BARRIERS IN PENTAD IENY LLITHIUMS ......... 34

INTRODUCTION © © © © © © © * © © ©■© © © © © © © © © © » © © 35

Structure and Rotational Barriers of Pentadieny1An 1 ons © © « « © © « © © © © © © « © « © © © © * © « © . 35

Structure and Rotational Barriers of Ally! Anions © © © © 36

v

VI

TABLE OF CONTENTS--Continued

• PageRotational Barriers of Allyl and PentadienylCatrons © O C C O C C O O O G O O O C O O G C O O O e O 41

EXPERIMENTAL ® ' e © o o ® e o e © © e o o © o e o © e o o e o 43

Synthesis of Pentad ienyl lithium © © © © © ® © * © © © © © 43

DISCUSSION OF RESULTS © * , . © © © © © © © © © © © ©,© © © © 46

NMR Spectra of Pentadienyl Anions © © © © © © © © © © © © 46Rotation in Anions « © © » © © © © « © © © © © © © © © © 66Sigmatropic Rearrangements of Pentadienyl Anions © © © © 75Conelus rons © © © © © © » © © © o © © © © © © © © © © © © 73

LIST OF REFERENCES © © © © © © © © © © © © © © © © ©. © © © © © © 79

LIST OF ILLUSTRATIONS

Figure ■ . "Page

lo . "NMR spectrum of lithium enolate and ethylene e • « * * 16

;2o NMR spectrum of lithium 3-methy.lenolate andpropy 1 ene © o © © « © © © © © © © © .© . .© ■© © © © © © © -.© 16

3© NMR parameters for lithium enolate at.35° © © © * © © © 17

4© NMR parameters for lithium 3-methylenolate at 35° * © © 17

. 5© Kinetic curves for reaction (5) at 35° © © © © © © © © 19

6© a- versus cleavage of substituted tetrahydrofurans © 23

7© NMR spectrum of anion (15) • © © © © © © © © © © © © © 31

8© NMR parameters for anion (15) at 35° © © © © © © © © © 32

9© NMR .spectrum of 1,4-hexadiene © ........... 47

10© NMR spectrum of anions (24) and (25) © © © © © © © © © 47

11 © NMR spectrum of 5-methyl-l,4-hexadiene © © © © © © © © 48

12© NMR spectrum of anions (26), (27), and (28) © © © © © © 48

13© NMR spectrum of 2,6“dimethyl-2,5-hexadiene © © © © © © 49

14© NMR spectrum of anion (29) © © © © © © © © © © © © © © 49

15© NMR spectrum of anions (30) and (31) © » © © © © © © " © 50

16© NMR spectrum of 1,4-octadiene © © © © © © © © .©. © © © © 50

17 © NMR spectrum of anion (32) © © © « © © © © © ♦ © © © © 51

18© NMR spectrum of isopropyl-1,4-pentadiene © © © © © © © 51

19© NMR spectrum of anions (33) and (34) « © © © © © © © ©. 52

20© NMR spectrum of anions (35) and (36) © © . © © © . © © 52

21© NMR spectrum of 2-methyl-l,4-pentadiene » « © © © © © © 53

vii

viii

LIST OF ILLUSTRATIONS--Continued

Figure Page

22. NMR spectrum of anion (37) e e . 0 . c c 6 © ■• o 53

23. NMR spectrum of Z^-dimethyl- 1,4--pentadiene . 6 ° c ° 54

24. NMR spectrum of anion (38) • o . O ° o G ° 54

25. NMR spectrum of 3-methyl--ls4-pentadiene o O e 6 . ° ©' . 55

26. . NMR spectrum of anion (39) . • '. c • ° o. O e • 0 6 © 55

27. NMR parameters for pentadienyllithium at 45° © o * ° © 56

28. NMR parameters for anion (24) at 50° ° c c c e © © 56

29. NMR parameters for anion (25) at 50° c . . . 6 e 6 6 • 57

30. NMR parameters for anion (26) at 50° o . . . • ° ° 6 57

31. NMR parameters for anion (27) at 40° 0 . o e c c ° ° • 58

32. NMR parameters for anion (28) at 40° 6 . . . • • 6 ° • 58

33. NMR parameters for anion (29) at 35° o e . ° 6: • 59

34. NMR parameters for anion (30) at 40° 0 . . c . © © • 59

35. NMR parameters for anion (31) at 35° ' . . . o C • • 60

36. NMR parameters for anion (32) at 35° 0 • 6 © © 60

37. NMR parameters for anion (33) at 40° 0 « . e © • 61

38. NMR parameters for anion (34) at 40° » . • ° • • 61

39. NMR parameters for anion (35) at 40° e . c . • . e © 62

40. NMR parameters for anion (36) at 40° 6 * * 6 * . © © • 62

41. NMR parameters for anion (37) at 35° 0 C O . ° ° • • 0 63

42. NMR parameters for anion (38) at 35° / • • • 63

43. NMR parameters for anion (39) at 35° . . . . 6 • • • 64

44. Sigmatropic rearrangements of anions . « . 77

LIST OF TABLES

Table • Page

Part I

l.o Decomposition rates of n-decyllithium « « « « ,* . e « « 5

2o Reaction of substituted tetrahydrofurans with.n-buty 1 llthlUmS o © o - » e - o o o o e o e ® o o e o o o o 1 1

3e Preparation of pentadieny11ithium in varioustetrahydrofurans , , » * « * e o « * * * * « * . « * e . 14

4e Relative rates for cleavage reactions at 35°. e e o » 26

5o Solvation studies on tetrahydrofurans at 35° «, <, o o o o 27

Part II ,

60 Rotation barriers in phenylally1 anion « o® oo e oo o 39

7 o Preparation of pentadienyHithiums o o o o . o o o o o o o 45

So Equilibrium concentrations, of cis- and trans-anions » c 68

9 o Rotation barriers in pentad ieny Hi thiums e «, e «> « o e 6 71

ix

ABSTRACT

Various tetrahydrofurans are reacted with n-butyllithium* Two

types of cleavage reactions are encountered- and possible mechanisms for

these reactions are discussed0 A new9 high yield synthesis of lithium

enolates of aldehydes is presented? which appears to occur via an elec-

•trocyclic mechanisme

Various pentadienyllithiums are produced by treating l94-penta-

dienes with n-butyllithium in hexane-tetrahydrofuran?. and a new posi

tional isomerization reaction possibly involving a 1,6-sigmatropic

proton shift is observed in some cases*

Variable temperature nuclear magnetic resonance studies of the

carbahions are run to get information on the effect of substituents on

rotation barriers* Most of the rotation barriers are <15 kcal/mole?

but with a pentadienyl carbanion containing one or more terminal alkyl

groups? the rotation barrier about the carbon-carbon bond to which the

alkyl group is attached is >19 kcal/mole* A mechanism involving momen

tary formation of covalent-lithium bonds is used to account for the

differences in rotation barriers in the various anions*

PART I

CLEAVAGE OF TETRAHYDROFURANS IN n-BUTYLLITHIUM

1

INTRODUCTION

Tetrahydrofuran (THF) is a .common solvent for many reactions

involving.organometallic reagents such as anionic polymerizations and

metallation reactions with alky111thiumso It is well known that organ

ometallic compounds decompose in THF and other ethersc The investiga

tion presented in this part of the dissertation deals with the reaction

of n-butyllithium with various tetrahydrofurans0 A news high yield

preparation of lithium enolates of aldehydes is presented0

Stability of Organometallic Compounds in THF

In 1910 Schorigin observed that ethyl ether reacts with ethyl-

sodium to produce ethylene, ethane, and sodium ethoxide* Since that

time there have been many reports on the cleavage of ethers by organo

metallic reagents, but only a few of these have dealt directly with

THF 6Wittig and Ruckert (1950) observed that THF, when complexed

with triphenyIboron, could be cleaved by triphenylmethyIsodium (1)* A

later study (Normant 1954) showed that THF can be cleaved by a Grignard

reagent at temperatures above 200° to give compounds of the type

R(CH^ÔHo Both of these reactions appear to take place by displace

ment of the ether oxygen by the organometallic compound*

In 1956 Letsinger and Pollart, while investigating o versus

^-elimination in the cleavage of ethers, reacted OO-phenyltetrahydrofuran

2 '

3

© ©+ ( C ^ ) ^ Na > c h2-c h 2 ©

Na

CH — CH2

(C6H5)3C 0H(1)

with propyIsodium. The products isolated were acetophenone, 1-pheny1-

ethanol, and 2,3-diphenyl-2,3-butanediol. Analysis of the gases evolved

showed the presence of ethylene and propane. The diol and phenylethanol

were theorized to be reduction products of acetophenone since small

quantities of metallic sodium were present in the propyIsodium mixtures.

To show that this was the case, cc-phenyltetrahydrofuran was reacted

with propyHithium in ether to produce acetophenone (85-92%), but no

reduction products. Pheny H i thium also cleaved cc-phenyltetrahydrofuran

in the same manner. 1

to explain the isolated products is shown in (2). Initial attack is on

the a-position, which is similar to the cleavage of ethyl benzyl ether

shown in this same publication. This was further substantiated by the

observation that THF itself, when treated with propyIsodium in hexane

at 50° for two hours, did not react.

A mechanistic sequence proposed by Letsinger and Pollart (1956)

4

+ RH

CHII 0 © H O 0

IIC H + C,H_C-0 M2 4 6 5 ^ c 6h 5c-c h 3

(2)

More information concerning the stability of organolithium com

pounds in tetrahydrofuran was presented by Gilman and Gaj (1957).

Methyl-, n-butyl-, and phenyllithium were prepared in tetrahydrofuran

and their relative stabilities were measured. It was found that these

three organolithium reagents are less stable in THF than in ethyl

ether, but their relative stabilities remain the same in either solvent,

namely, methyl- > phenyl- > n-butyllithium (Gilman, Haubein, and Hartz-

feld 1954; Haubein 1943). It was reported that the workable temperatures

for methyl-, n-butyl-, and phenyllithium in THF are 0°, be low -35°, and

0° to -30°, respectively.

added further evidence on the instability of alkyHithiums in mixed

ether solvent systems. These studies showed that the decomposition of

the alkyHithiums was markedly increased when tetrahydrofuran-ether

mixtures were used as compared to ether alone. Table 1 shows the de

composition rates of n-decyHithium in various solvent systems.

An investigation carried out by Gilman and Schwebke (1965)

5Table 1. Decomposition rates of n-decyllithium.

Solvent k^(h 1) ^0.5^)

Diethyl ether-tetrahydrofuran 0.598 1.2

Diethyl ether-tetrahydropyran 0.045 15

Diethyl ether-2, 2,4,4-tetramethyItetrahydrofur an 0.0104 67

Diethyl ether 0.0096 72

Rembaum, Siao, and Indietor (1962) reported that ethyllithium

decomposed in THE at 25° to give, upon hydrolysis, ethane, ethylene,

acetaldehyde, and hexanol. The following reaction paths (3) were used

to explain these products. Both of these pathways have been mentioned

previously (Letsinger and Pollart 1956, Normant 1954).

EtLi +

> Et(CH ) OH

+Li OH 4/

H2° 0 0 LiOH + CH CHO <— -— CH2=CHO Li +

(3)

• 6Mechanisms of THF Cleavage Reactions

The simplest mechanism for OC-cleavage of THF has already been

presented in this introduction and involves the abstraction of an GO

proton followed by a shift of electrons until ethylene and enolate are

eliminated* This mechanism.was used to explain the hydrolysis products?

but no evidence for its existence was presented*

If alkyl substituents are placed on the COposition of THF? the

possibility of a" -elimination is greatly increased» The mechanism of

this cleavage reaction with alkyl ethers has been investigated by Let-

singer and Bobko (1953)* Their studies on the reaction of butyllithium

with cis and'trans isomers of methyl 2-phenylcyclohexy1 ether indicated

that the trans•isomer was converted to 1-pheny1eye1ohexene faster than

the cis isomer* Since methyl cyclohexyl ether and butyllithium did not

react under the conditions employed for the phenyl-substituted ethers5

it was assumed that a p-proton was abstracted in the reaction* There-,

fore, in this case cis elimination was faster than trans elimination*

A proposed path for the reaction is shown below (4). This cyclic tran

sition state is similar to ones postulated for pyrolytic elimination

reactions* A similar mechanism was proposed by Gould, Schaaf, and

Ruigh (1951) for the cleavage of cholesteryl ethers with aIkyIsodiums»

+ LiOCH

(4)

Solvation Effects of Substituted Tetrahydrofurans

Since in the investigation described in this dissertation the

tetrahydrofurans treated with n-butyllithium were also used as solvents

for the reaction, their solvating ability may have an effect on the re

action, and pertinent literature will now be reviewed.

Chan and Smid (1968) made a study on the role of solvent struc

ture in alkali ion solvation. Their results showed that 2-methyltetra-

hydrofuran is a much poorer solvating solvent than THF, and 2,5-

dimethyItetrahydrofuran is even worse. These two solvents contain

substituents in the a-position. When a methyl group was placed on the

|3-position of THF, it was found that the solvating ability was not much

different than THF; this seemed reasonable since the substituent was

situated nearer to the periphery of the solvating shell.

The results of Gilman and Schwebke (1965) mentioned earlier

also could indicate a solvation effecte The decomposition of n-decyllithium in ether - 2,2,4,4-tetramethyltetrahydrofuran was much slower

than in ethe'r-THF*

EXPERIMENTAL

Nuclear magnetic resonance (nmr) spectra were recorded at 100

MHz on a Vartan HA-100 spectrometere Infrared (IR) spectra were re

corded on a Perkin-Elmer Infracord Spectrophotometer Model 137 Be Mass

•spectra were determined on a Hitachi-Perkin-Elmer RMU-6E Double Focus

ing Mass Spectrometero The EPR spectra were recorded on a Varian E-3

Spectrometero Kinetic data were analyzed using a Pace -TR-10 Analog

Computero Liquid scintillation counting was done with a Nuclear-

Chic ago "Mark I" Liquid Scintillation Counter0 The tetrahydrofurans

obtained commercially were dried over 4”A molecular sieves activated

by heating at greater than 200° for at least 8 hourse

Reaction of THE With n^Butyliithium

Commercial (Foote Mineral Company) n-butyllithium (0,5 ml,

0,0008 mole) was added to dry tetrahydrofuran (1,0 ml, 0,012 mole) in

ah nmr tube, and the reactants were thoroughly mixed. After a few min

utes the solution turned pale yellow. The reaction was essentially

complete after about seventy minutes,

The gaseous products given off in this reaction were collected

in a gas collection tube fitted with IR plates, and these products were

analyzed by infrared spectrophotometry and mass spectrometry.

The reaction of n-butyllithium with the remaining tetrahydro

furans was run in^the manner described above. In all cases 0,5 ml of

9

10n«butyllithium was used6 Table 2 indicates the quantities of tetrahydrofurans used 0 .

Lithium Enolate c 2THF

Tetrahydrofuran (lo0 ml) and n-butyllithium (4.0 ml) were thor

oughly mixed in a test tube and allowed to stand for six days, by which

time crystals had formed. The top layer was decanted off and the crys

tals were washed several times with dry heptane and redissolved in

THF .g6 Nmr spectra were taken of the upper layer and the redissolved

crystals.

Hydrolysis of Lithium Enolate

THF (4.0 ml) and n-butyllithium (2.0 ml) were thoroughly mixed

in a test tube and allowed to react for 2 hours. The resulting solu

tion was placed in a dropping funnel fitted to a three-necked, round-

bottomed flask containing a condenser and a ground-glass stopper.

Excess water (10.0 ml) had been placed in the flask and cooled to 0°.

The solution of lithium enolate was added slowly to the reaction vessel

with.rapid stirring. After all of the enolate was added, the reaction

mixture was distilled and the acetaldehyde was collected and identified

by its infrared and nmr spectra.

Tritiation of Tetrahydrofurany1 Anion

Tetrahydrofuran (10 ml) and n-butyllithium (5 ml) were mixed in

a flask and after 4 minutes THO (180 X ) was added. The mixture was al

lowed to stir for 5 minutes and then the flask was placed in a hot water

bath to drive off the dissolved ethylene and butane. Lithium aluminum

11

Table 2* Reaction of substituted tetrahydrofurans with n~buty11ithiums»

Compound Source ml

2-me thy11e tr ahyd rofur an ' - b V 0.60

2,2-dime thyItetrahyd rofuran / c 0.672,5-dime thyItetrahydrofuran a 0.67

7-oxo-b icyc1o[2.2.l]heptane a 0.66

3,4-dime thyltetrahydrofuran d ^ 0.67#

o (a) Aldrich Organic Chemical Co., (b) Eastman Organic Chemicals, (c) Chemical Samples Co., (d) see Experimental.

#. This quantity includes a small amount of pentane.

12hydride(0o09 g) was added and the reaction mixture was refluxed for

30 minutes c Distillation of the mixture afforded about 8 ml of mater

ial boiling at 62°. A sample (10 X) was removed to be used on the

scintillation counter. r

The scintillation solution was prepared by mixing 2,5-diphenyl-

oxazole (4 g) and 194-biS”2eM(4-methy 1-5-phenyloxazolyl)-benzene in

toluene (1 Titer).

A standard sample was prepared by adding” n-butyllithium (5 ml)- * . . .

to THO (180 X) followed by addition of THF (10 ml). This sample was

dried in the same manner as described previously.

Deuteration of Tetrahydrofurany1 Anion

Tetrahydrofuran (2.0 ml) and n-butyllithium (1.0 ml) were mixed

in a flask and after 4 minutes the reaction was quenched with deuterium

oxide (Stohler Isotope Chemicals). A sample of the liquid was taken

for.mass spectral analysis.

Hydrolysis of Tetrahydrofuranyl Anion

The above procedure was repeated, but water was added" after 4

minutes. A sample of the liquid was taken for analysis on the mass

spectrometer.

3,4-Dime thy11e trabydr ofur an

A 200-ml round-bottomed flask was equipped with a Soxhlet ex

tractor and a magnetic stirring unit. Into the reaction vessel was

placed 0.9 g of LiAlH^ (0.023 mole; Metal Hydrides) and 100 ml of■an

hydrous ether. The extraction thimble contained 2.3 g of

132$S-dimethylsuccinic acid (0,016 mole; Aldrich Organic Chemical Com

pany) , The ether was maintained at a moderate rate of boiling by means

of an electric heating mantle until all the diacid in the thimble had

dissolved. The reaction flask was cooled to 0° and H O (6 ml) was

added slowly with stirring. After stirring at ropm temperature for one

hour9 the ether layer was decanted and used to extract the solid resi

due for 24 hours in a Soxhlet extractor. The solvent was removed by

distillation at atmospheric pressure through a 15-inch Vigreux column

and then by evacuation for 4 hours, Air was admitted to the apparatus

and 0,2 ml of 857, phosphoric acid was added, After refluxing for 2

hourss all material boiling-below 100° was distilled into the receiver.

This material was dried by running it through a column packed with

basic Alumina9 activity 1 (J, T, Baker Chemical Company); the solvent

used was pentane, Most of the pentane was removed by distillation and

the remaining material was shown to be 394-dimethyItetrahydrofuran by

nmr. The yield was about 0,5 g (30%).

Preparation of PentadienyHithium in Various Tetrahydrofurans

Commercial (Aldrich Organic Chemical Company) 1$4-pentadiene

(0,15 ml) was added to n-butyllithium (0.80 ml) in the various tetra

hydrofurans at -78°, The reactions were followed immediately by nmr

and a relative tL was determined by following the downfield multiplet

due to the pentadieny1lithium. Table 3 shows the quantities of the

tetrahydrofurans used in. the reaction.

14

Table 3. Preparation of pentadienyllithium' in various tetrahydrofurans«

„Compound ml

tetrahydrofuran 0.11

2~me thyltetrahydrofuran 0.12

2g2-dimethyltetrahydrofuran 0.14

2,5“dimethyltetrahydrofuran 0.14

•7"Oxo”bicyclo[2,2, l]heptane 0.13

DISCUSSION OF RESULTS

It has been known for some time that tetrahydrofuran (THE)

reacts with alkyllithium compounds* In this part of the dissertation

the reaction between some tetrahydrofurans and n»butyllithium is pre

sented o A new high-yield synthesis of lithium enolates of aldehydes

is describedo

Preparation of Lithium Enolate

. The reaction between THE and n-butyllithium produces lithium

enolate and ethylene in quantitative yield as shown by the complete

disappearance of the n-butyllithium and appearance of only enolate and

ethylene0 The nmr spectrum shown in Figure 1 consists of a downfield

quartet at T 3,12 and an upfield quartet at T 6,85 due to enolate and

a singlet at T 4,7 due to ethylene* The other quartet associated with

enolate absorbs in the same region as'THE (T 6,4), The chemical shifts

in T units and coupling constants in Hertz (Hz) are shown in Figure 3,

Upon hydrolysis acetaldehyde was obtained, . The ethylene produced was

identified by its nmr$ infrared, and mass spectra. Lithium enolate was

found to be stable in THE for at least six months when stored in a

sealed tube under nitrogen. Crystalline lithium enolate was prepared

by mixing equimolar quantities of THE and n-butyllithium and allowing

this to stand for six days * The nmr spectrum of these crystals dis

solved in perdeuterotetrahydrofuran seems to show that two moles of THE

are associated with each mole of lithium enolate,

15

S-s-H

-n16

Figure 1. NMR spectrum of lithium enolate and ethylene.

Figure 2. NMR spectrum of lithium 3-methylenolate and propylene.

17

HaHe

Chemical Shifts (T)

Ha 3.12

Hb ^ 6.4

He 6.85

Figure 3. NMR parameters for

Coupling Constants (Hz)

Jab 12.8

Jac 4.8

Jbc 2.0

ithium enolate at 35°.

Ha

Hb

Chemical Shifts (T) Coupling Constants (Hz)

Ha 3.37 Jab 11.0

Hb 6.3

Figure 4. NMR parameters for lithium 3-methylenolate at 35°.

The enolate from propionaldehyde was prepared by treating 3,4

dimethyltetrahydrofuran with n-butyllithium. The nmr spectrum and the

nmr parameters for this anion are presented in Figures 2 and 4, respec

tively.

Mechanism for Cleavage of Tetrahydrofuran

It is proposed that the following reaction sequence was taking

place (5). Since a 15-fold excess of THE was used, the first step is

pseudo first-order in butyllithium. The kinetic expressions that

apply are the following:

This reaction was conveniently followed by observing the de

crease of the methylene peaks a t T 11 due to the n-butyllithium and the

increase in the quartet at T 3.1 due to enolate in the nmr spectrum.

The set of curves (Figure 5) produced was matched as well as possible

using an analog computer. The rate constants obtained at 35° were

+ BuLi -BuH >

(THF©) (EG)

(5)

Peak

He

ight

(c

m.)

19

24t x I0 2 (sec.)

3630 42

Figure 5. Kinetic curves for reaction (5) at 35°.

A n-butyllithium o Lithium enolatePoints are experimental, curves are computer-drawn

' 20From the curves it was observed that the•intermediate (presum

ably the anion shown) reached, its maximum concentration of about 10%

after 4 minutes * Because of this finding, it seemed possible to gain

evidence regarding the structure of this 'intermediate in another manner*

To do this, two different methods were employede

In the first procedure, after 4 minutes the reaction mixture

was quenched with THOe The THF recovered from the reaction was then

purified and its radioactivity measured* The results of this experi

ment suggested that the THF anion was present, but quantitatively the

results were poor because the background count of the standard sample,

prepared by mixing THF with THO &nd then purifying the THF, varied

greatly*The second procedure consisted of adding DÔ to the sample after

4 minutes of reaction* Comparison of the mass spectrum of the deuter-

ated material to a standard sample in which-H O was added resulted in a

calculated concentration for the THF anion of 8%* From these observa

tions, it seems clear that this anion is an intermediate in the cleav

age reaction*

From the above data, the following possible mechanisms were

proposed (I and II)e A third possibility is a free radical dissocia

tion of the tetrahydrofuranyl anion (THF©) e

A free radical mechanism was rendered somewhat less likely on

the basis that no radicals could be detected when the reaction was

followed by ESR* '

21

I+ BuLi > CH =CHOLi + CH CH

To differentiate between mechanism I and II one can look at the

products obtained with cc-phenyltetrahydrofuran and 2-methyltetrahydro-

furan. In the case of a-phenyltetrahydrofuran the proton next to the

phenyl ring would be the most acidic and would be abstracted by

n-butyllithium to give (6). If this anion decomposes by mechanism I,

(6)

the products upon hydrolysis would be acetophenone and ethylene which

were the products obtained (Letsinger and Pollart 1956). If mechanism

II were operating, the products on hydrolysis would be acetaldehyde

and styrene, but these products were not detected. If 2-methyltetra

hydrofuran is considered, one of the two secondary CC~protons would be

expected to be abstracted faster than the tertiary (X-proton. This is

a reasonable assumption since secondary carbanions are more stable than

22tertiary carbanions and because no a-protons are abstracted when 2,5-

dimethyltetrahydrofuran is reacted with n-butyllithium. If, after

forming anion (7), mechanism I proceeds, the products would be lithium

enolate and propylene which are the products obtained. The products

expected if mechanism II were operating would be the enolate of acetone

(7)

and ethylene, neither of which was detected. These results seem to in

dicate that mechanism I is the favored process. This seems to be an

example of a 4 + 2 electrocyclic reaction which is thermally allowed

cis-cis according to Hoffmann and Woodward (1968).

PC- Versus 3-Cleavage of Substituted Tetrahydrofurans

In attempts to prepare other lithium enolates by the aforemen

tioned procedure and to further investigate the cleavage reaction, sub

stituted tetrahydrofurans were obtained and reacted with n-butyllithium.

In doing these experiments it was noticed that another type of cleavage

was taking place in some cases. In the reactions discussed, (X-cleavage

is defined as the abstraction of an a-proton by n-butyllithium followed

by a retro-cycloaddition reaction and 3 -cleavage as an elimination re

action triggered by the abstraction of a 3-proton. Figure 6 illustrates

23

CH. G+ 0 ^ 0 + /

(8)

C H ^ X T ' c h3(9)

CH.

CH.■> ©

(10)

(11)

CH a i3

+ = /

(12)

Figure 6. a- versus ^-cleavage of substituted tetrahydrofurans,

24reactions investigated in.this part of the dissertation. In all cases

an excess of the cyclic-ether was used»

Possible Mechanism for g-Cleavagei i i-nmm 8ii mr»ini, MWjiwnm, it in nwiuu l .... i i ijw* wniTi.it%» i^*. —

In the course of investigating the cleavage reactions between

n-butyllithium and substituted tetrahydrofuranss some observations were

made on the mechanism for p-cleavage,

Tetrahydrofuran-itself contains four j3~protons available for the

p-cleavage, but this type of reaction was not detected. Models of THF

show that none of these protons can, without considerable strain, reach

the proper geometry for a facile cis- or trans-elimination process, In

cases where methyl groups are attached to the apposition of THF [(8),

(9), and (10)], both cis~ and trans-g-elimination processes are.geomet

rically possible. These compounds do give g-“cleavage reactions, When

a model is made of 7-oxo-bicyclo[.20 2® l]heptane (11), a trans-elimination,

seems possible with very little twisting of the ring, but a cisêlimina

tion reaction is not possible. Since this compound does not undergo a

g-elimination reaction (<2%), this seems to be indirect evidence for a

cin-elimination process. This type of. elimination could take place via

a six-membered ring transition state (13).as proposed by Letsinger and

Bobko (1953) for the reaction between n-butyllithium and the cis and

trans isomers of 2-phenyl eye lohexyl ether. In all cases where-f3-cleavage

occurred, this type of transition state was geometrically possible.

Solvation Effects in the Cleavage Reactions

It was observed that some of the tetrahydrofurans investigated

containing (X-protons did not undergo observable CC-cleavage since

another cleavage reaction occurred faster. In the case of 2,5-dimethyl-

tetrahydrofuran (9), both of the Oc-protons are tertiary and this might

explain the inability of this compound to Ct-cleave, but this cannot be

the reason for 2,2-dimethyltetrahydrofuran (10) not reacting in this

manner since this compound contains two secondary a-protons. Looking

at the relative rates for CC- and (3-cleavage (Table 4), it is obvious

that some other factor is entering into the picture.

A possible explanation of these observations might be obtained

by examining the solvating abilities of the various tetrahydrofurans.

This was done by following with nmr the reaction of n-butyllithium with

1,4-pentadiene using the various tetrahydrofurans as the solvent. The

approximate half-lives for the production of pentadienyllithium at 35°

are shown in Table 5. From this table, it can be seen that as methyl

groups are placed on the a-position the solvating ability of the cyclic

26

Table 4e Relative rates for cleavage reactions at 35°*

Ether\

a-cleavagea tL (sec)

P -cleavage^3t, (sec)% -

THE 6 x 102 -

2-methyl THE 4 x 103 . 2.0 x 103

2,2-dimethyl THE >1 x 105 4.2 x 104

2,5-dimethyl THE >1 x 105 3.5 x 104

3,4-dimethyl THE 4 x 103 c -

7-oxo«bicyclo[2<> 20 l]heptane 6 x 102 “

ae Rate per secondary a-p'roton

be Rate per (3-proton not in ring

cc This should not be compared to the others since somepentane was present as an impurity in this ether and the polarity of the solution was lower in this case.

27

Table 50 Solvation studies on tetrahydrofu'rans at 35°©

Solvent for formation of pentadienyllithium (sec)

THF 200

2-methyl THF 700

2;2-dimethyl THF 2800

2,5-dimethyl THFa 1300

7-oxo-bicyclo[2o 2.l]heptane ~ 200

a* Mixture of cis- and trans-isomers0

ether decreases. These results are in agreement with a study done by

Chan and Smid (1968) on steric effects in solvation.

The above solvation studies seem to correlate the observed

cleavage reactions. The g-cleavage reactions proceed more slowly as

more methyl groups are placed on the OC-position. Placing of two methyl

groups on one Ct-position causes slower 3-cleavage than if one methyl

group is placed on each a-position and this is what is expected accord

ing to the solvation studies. This suggests that the first step in the

reaction is the formation of an ether-buty11ithium complex (14) which

further reacts to give the observed products.

+ nBuLi

(14)

If this concept is applied to the Ct-cleavage reactions, the

same effect is seen when comparing THE and 2-methyl THE, but 2,2-

dimethyl THE does not give any a-cleavage although this material con

tains two secondary CC-protons. A possible explanation here is that in

the ether-butyllithium complex of this compound the ether molecules are

situated farther from the butyllithium than with THE because of steric

reasons and this makes it more difficult to abstract an CC-proton, but

the formation of a six-membered ring transition state for 3"•cleavage is

still possible. In the case of the 2-methyl THE the ether molecules

are close enough to the n-butyllithium to allow both types of cleavages.

Rotation Barriers in Lithium Etiolates

Since it was possible to prepare lithium enolate (Figure 3) in

high concentrationsj, an attempt could be made to measure the rotation

barrier in the anionc At room temperature the terminal protons of

lithium enolate are nonequivalent and thus cause the central proton to

appear as a quartet in the nmr spectrum* If the anion could be heated

to a .high enough temperature, rotation would occur faster about the

carbon-carbon bond, the terminal protons would become equivalent, and

the central proton would appear as a triplet* Lithium enolate was

heated to 125% but no change in the nmr spectrum was observed * Appar

ently the barrier to rotation is quite high (AG >20 kcal/mole; see

Part II for mode of calculation)* This barrier contrasts with the very

low one (11 kcal/mole) in allyllithium (West, Purmort, and McKinley

1968)o Apparently covalent bond-forming collisions to carbon are rare

in this anion (see Part II for mechanism for rotation), partly due to

its great stability as compared to allyl anion and partly since colli

sions may occur predominantly at the more electronegative oxygen (an

invisible process)0 This charge distribution is further illustrated by

comparing the chemical shifts of the terminal hydrogens in lithium eno

late and allyllithium, which are T"6*6 and T 7*8, respectively* Bates,

Gosselink, and Kaczynski (1967b) have shown that the more electron den

sity a carbon possesses, the further upfield the hydrogens attached to

’that carbon absorb in the nmr spectrum*

A related anion (15) was produced by treating 2,5-dihydrofuran

with n-butyllithium* The nmr spectrum of this anion is shown in

Figure 7 and the nmr parameters in Figure 8. This anion was also

heated to 125° to obtain a barrier to rotation about the C1 _ bond.1-2Again the nmr spectrum showed no change and the barrier to rotation

about this bond is assumed to be quite high (A G*> 20 kcal/mole).

The nmr parameters of anion 15 indicate that it is sickle

shaped or possibly U-shaped. In the preparation of this anion, the

U-shaped anion should be formed initially and this probably rapidly

rotates about the ^ bond to the sickle-shaped anion. This is con

sistent with the idea that the major contributing resonance form is

16. This also explains the high barrier to rotation about the

bond and its apparent failure to equilibrate with the presumably more

©(15) (16)

stable W-shaped ion. This anion was heated to 150° in a sealed tube

and then cooled, but this failed to produce any change. This indi

cates either that the barrier to rotation about the bond is quite

high (AG^ >23 kcal/mole), or that the sickle-shaped anion shown is the

most stable. Decreased negative charge on the terminal carbon is sug

gested by the difference in chemical shifts of the terminal hydrogens

in anion 15 and pentadieny11ithium, which are T 5.6 and T 7.0, respec

tively.

31

Figure 7. NMR spectrum of anion (15).

32

Ha Hb


Ha 3.30 Jab 6.0

Hb 5.42 Jbc 10.5

He 3.26 Jed 17.0

Hd 5.48 Jce 10.5

He 5.75 Jde 2.0

\

Figure 8. NMR parameters for anion (15) at 35°.

33

Conclusions

In this part of the dissertation a new high yield synthesis of

lithium enolates of aldehydes has been presented, The only other sub

stances produced are gaseous materials which can easily be removed.

This reaction appears to proceed by an electrocyclic mechanism. An in

vestigation of the stereochemistry of the reaction would be of inter

est: from the Woodward-Hoffmann rules, an anion like 17 would cleave

to a cis olefin.

Z

(17)

PART II

ROTATION BARRIERS IN PENTADIENYLLITHIUMS

34

INTRODUCTION

Pentadienyl carbanions have been proposed as short-lived inter

mediates in base-catalyzed isomerizations of 19 3- and ls'4-dienes (Birch

1950| Birch? Shoukry8 and Stansfield 1961| Krapcho and Bothner-By 1959)9

Birch reductions of aromatic compounds? and in nucleophilic substitu

tion reactions (Bunnet and Zabler 1951? Miller 1963)» A recent prepara

tion of pentadienyllithiums in high concentrations (Bates? Gosselink?

and Kaczynski 1967a) has now made this class of compounds available for

study and this part of the dissertation deals with the effect of sub- .

stituents on rotation barriers in these anions and the mechanism involved

in these rotationse In this introduction? a discussion of the work al

ready done on pentadienyllithiums will be presented first? followed by

a brief description of allyl carbanions, lower vinylogs of pentadienyl .

anionse Lastly, corresponding studies on pentadienyl and allyl cations; ' . }

will be summarized0

Structure and Rotational Barriers of Pentadienyl Anions

The bonding in organometallic compounds has been of interest

for many yearse The carbon to metal bond in simple alkyllithiums has

been shown to be largely covalent (Cheema, Gibson, and Eastham 1963).

Some alkyllithiums probably exist mainly as solvent separated ion pairs

(Hogen-Esch and Smid 1966)0 The bonding in triphenylmethyllithium ap

pears to be ionic since the nmr spectrum is independent of cation and

solvent (Sandel and Freedman 1963)e

■

36

Bates? Gosselink? and Kaczynski (1967a,b) reported on the prep™

aration and nmr study of pentadienyHithium0 The probe temperature nmr

spectrum of this substance consisted of a multiplet at T 308 due to the

protons attached to carbons 2 and 4, a triplet at T 5*9 due to the cen

tral proton, and a broadened absorption at T 7«,0 due to the four termi

nal protonso Upon warming to 40°, two sharp peaks developed in the

T 7o0 region, and cooling to 15° produced four peaks in this region0

The temperature dependence of the nmr spectra was explained as being

due to an exchange process that makes the terminal protons equivalent

slightly above probe temperature0 From these data it was concluded

that, since the low temperature spectrum cannot be explained by rapid

equilibration of covalent species (Norlander and Roberts 1959), the

compound must be greater than 90% ionice A proposed mechanism for the

exchange process consisted of a collision between a carbanion and a

lithium ion to form a covalent bond for a sufficient amount of time to

permit rotation about the resulting carbon-carbon single bondse

Structure and Rotational Barriers of Allyl Anions

The nmr spectrum of allylmagnesium bromide was shown to be

simple AX^ pattern in ether solution (Norlander and Roberts 1959)0 The

spectrum consisted of a downfield quintet due to the central proton and

an upfield doublet due to the terminal protonse This spectrum was in

terpreted on the basis of a rapid equilibrium of two covalent forms

(18)* Structures such as 19 and 20 could also explain the observed

data, but these were ruled out because the authors felt the multiple.

37

BrMgCH CH=CH ~ ^ CH =CHCH MgBr

(18)

MgBr CH •' ".CH"Mg'"Br

(19) (20)

bond character (p^^ = 0.707) (Streitwieser 1962) makes the barrier to

rotation too high to be reasonable under normal conditions. In order

for the terminal protons to be in an pattern, the barrier to rota

tion about the bond must be low enough to allow averaging of these

protons. If rotation was not taking place, then the spectrum would be

expected to show an AA’BB’C pattern.

Early investigations of allyllithium (Johnson et al. 1961,

Grovenstein et al. 1966) did not lead to a definite decision on the co

valent or ionic nature of the compound. Infrared studies by Lanpher

(1957) on allylsodium, -potassium, -lithium, and -magnesium added evi

dence for a largely ionic structure.

Freedman, Sandel, and Thill (1967) reported on the geometric

stability of 1,3-diphenylallyllithium. The desired anion was produced

from the reaction of n-butyllithium in hexane-tetrahydrofuran with cis-

and trans-1,3-diphenyIpropene. The nmr spectra obtained in both cases

consisted of an AB^ pattern with = 13 Hz. This was consistent with

38the spectrum expected for trans-trans-1,S-dlphenylallyllithium (21).

The upfield shift of the phenyl protons indicated that there was

(21)

considerable delocalization of the negative charge into the phenyl

rings, and therefore the charge must be similarly distributed over the

allylic carbons. If a largely delocalized anionoid species was in

volved, then the anion would contain partial double bonding and a bar

rier to rotation. Using a calculated bond order of 0.66 for the

1,3-diphenylallyl anion, and assuming a correlation between bond order

and bond energy, the rotation barrier would amount to 27 kcal. This

calculation was based on a 40-kcal energy difference between a single

and a double bond. Since rotation took place even at -30°, it was as

sumed that there was an extraordinarily low AG* for rotation, but no

explanation was given for this discrepancy.

Rotation barriers in phenylallyl alkali metal salts were meas

ured by Sandel, McKinley, and Freedman (1968). The chemical shifts

of the central proton and £-phenyl proton indicated a trans geometry

about carbons 2 and 3 (22). An nmr temperature study of the lithium

compound showed that rotation about carbons 1 and 2 takes place rapidly

at 90° but is slow or absent at 5°. Studies using 3,5-dideuterophenyl-

allyllithium revealed that rotation about the phenyl-C^ bond is rapid at

39

H

H H(2 2)

5°, but slowed down at -58° to the extent that two different ortho-

protons can be observed. Data obtained for various alkali metals in

THF and ether is shown in Table 6.

Table 6. Rotation barriers in phenylallyl anion.

Metal SolventMe thylene Phenyl

Tca°C

A g^(t )kcal/mole

Tc°C

AC? (-15°)kcal/mole

Li THF 60 17.0 (55°) -31 11.9

Li ether 25 15.7 (55°) -77 10.3

Na THF 95 17.8 (95°) -15 12.9

Na ether -38 11.7

K THF 115 20.1 (115°) -15 12.9

a. Coalescence temperature.

It can be seen from this table that the barrier appears to increase in

general in going from lithium to potassium.

The authors (Sandel et al. 1968) found that the ratio of the

energy barriers of the t0 the phenyl-C^ was in good agreement with

the ratio of Huckel MO TT-bond orders. From these results it was

40

reasoned that the rotation occurs in a single? solvent- and cation- dependent partially delocalized structure*

The mechanism for rotation used by Bates et al0 (1967b) for

pentadienyl carbanions could also be applied to phenylallyllithium*

This mechanism would be cation and solvent dependent* As the cation

is changed from lithium to sodium to potassium? the ionic nature of the

bond increases and the formation of a momentary covalent bond becomes

less desirable* Since the degree of solvation of a metal ion depends

on the solvent used? the barrier to rotation will also be solvent de

pendent*

If calculations similar, to ones used by Freedman et al* (1967)

are done on phenylallyllithium? the barriers to rotation about the

bond and phenyl-bond would be 31 and 20 kcal, respectively* These

calculations were done using bond orders reported by Sandel et al*

(1968), These calculated values do not agree with the reported experi

mental values* Although these results alone are not enough to rule out

rotation in the anion itself? the results reported on the dependency of

rotation on the cation and solvent would tend to support the mechanism

used for pentadienyllithium* Further data on this point will be pre

sented in the Discussion section*

A variable temperature nmr study of allyllithium (West? Purmort?

and McKinley 1968) added more evidence to the ionic nature of these

compounds* At 370 all of the terminal protons are equivalent and an

AB^ pattern was observed* At -87°, the rotation about the carbon-carbon

41bonds is slowed to the extent that two distinct protons can be observede

Ultraviolet and infrared studies also indicated an ionic structuree

Rotational Barriers of Allyl and Pentadienyl Cations

Another class of related compounds are the allyl and pentadienyl

carbonium ions o

Deno and Pittman (1964) reported that the nmr spectrum of

:X,l.9555-tetramethylpentadienyl carbonium ion contained two resolved

peaks for the methyl groupse This indicated that the methyls are non™

equivalent due to slow or absent rotation about the bond*

It was noted by Deno and others (1963) that the nmr spectrum of

2$4-dimethyIpenteny1 cation showed two separate peaks for the methyl

groupseL

Olah and Bollinger (1968) measured actual rotation barriers in

alkenyl cations6 Their data seemed to show that rotation was not talc™

ing place by means of formation of a momentary covalent species* It

was assumed that the transition state for the rotations was an ion in

which the p-orbital of the carbonium ion is orthogonal to the TT-orbital

of the double bond * It was observed that in the case of 23 the olefinic

protons were nonequivalent* Apparently the rotation barrier about the

adjacent carbon™carbon bond is quite large*

42

CH

H

CH

(23)

EXPERIMENTAL

Nuclear magnetic resonance (nmr). spectra were run at 100 MHz on

a Varian HA-100 spectrometer. Using the Varian variable temperature

control unit) nmr spectra were obtained from -60 to 4-100°. The vari

able temperature control unit was calibrated using ethylene glycol for

high temperatures and methanol for low temperatures. All chemical

shifts are reported in T"units and coupling constants in Hertz. The

nmr spectra of the pentadienyl carbanions are not described in the Ex

perimental section^ but reproductions of them can be found in the Dis

cussion section. In the spectra of the anions9 no absorptions were

observed between T 0.0 and T 3.5.

Synthesis of Pentadienyllithium

Dry tetrahydrofuran (0.2 ml) and commercial (Aldrich Organic

Chemical Company) 1,4-pentadiene (0.10 ml) 0.001 mole) were introduced

into an nmr tube and cooled to -78°. Commercial (Foote Mineral Com

pany) 1.6 M in hexane solvent) n-butyllithium (0.8 ml, 0.0013 mole)

was added. The reactants were thoroughly mixed and allowed to warm to

room temperature. After about 5 minutes the reaction was complete and

two layers had formed. The orange lower layer was found by nmr to con

tain pentadienyllithium, tetrahydrofuran, and hexane'. The yellow upper

layer contained tetrahydrofuran and hexane.

The tetrahydrofuran used in this synthesis was dried by distil

lation from lithium aluminum hydride and stored over 4-A molecular

43

44sieves (activated by heating at greater than 200° for at. least 8

hours)« The rest of the pentadieny11ithiums studied were prepared by

this general procedure (Bates et al* 1967a) using commercial (Stohler

Isotope Chemicals) perdeuterotetrahydrofuran (0.2 ml) and 0.8 ml

n-butyllithiunic The quantities of dienes used and approximate times

for layer separation are shown in Table 7.

45

Table 7 <,. Preparation of pentadieny 11 ithiums 0

Diene . *Source ' Ml ofdiene

Approximate time for layer separation (hrs)

1,4-hexadiene a Oo 11 0.5

5-me thy 1 =* 1,4 "hexad iene a 0.13 0.8

2,6-d ime thy1-2,5-heptadiene c 0.16 48.0

l94-octadlene b 0.14 0.3

2,4-d ime thy1-1,4-pent adlene a 0.13 12.0

2-methyl-1,4-pentadiene a 0.11 0.2

isopropyl-1,4-pentad iene c 0.13& 0.3

3-me thy1-1,4-pen t ad i ene^ a 0.11 0.2

*• (a) Chemical Samples Co,, (b) Aldrich Organic Chemical Co.,(c) private communication6

a. This quantity is given in grams»

be Prepared in regular THF.

DISCUSSION OF RESULTS

In this study* lithium salts of acyclic pentadienyl carbanions

are prepared by the procedure of Bates et ale (1967a)* and the barriers

to rotation about the partial double bonds are calculated from the var

iable temperature nmr spectra* A sigmatropic rearrangement of these

carbanions is also presented0

NMR Spectra of Pentadienyj Anions

The nmr spectra of the starting dienes and the resulting carban- .

ions are presented in Figures 9 through 26* The conversions to the

anions were essentially quantitative since no dienes could be observed

in the spectra* The lock signal utilized for the anions was the methyl .

groups of. hexane at T 9e1 or the methylene groups at T 8*8, The lock

signal for the dienes was tetramethylsilane (TMS)6 Small absorptions at

T"8,30 and T 6,46 are due to residual protons on the deuterotetrahydro-

furan. In some cases more than one anion is present; the manner in

which these mixtures arose will be discussed later*

The coupling constants in Hertz (Hz) and chemical shifts in

units for the pentadienyl anions are presented in Figures 27 through

43* The approximate chemical shifts were calculated using hexane as an

internal standard *

Bates et al* (1967b) observed that the chemical shifts of the ■2protons attached to the sp carbons of the carbanion can be related to

the charge density on these carbons* The hydrogens attached to carbons

46

47

Figure 9. NMR spectrum of 1,4-hexadiene.

fztdr

Figure 10. NMR spectrum of anions (24) and (25).

Numbers in parentheses refer to anions presented in Figures 27-43.

48

Figure 11. NMR spectrum of 5-methyl-l,4-hexadiene.

_L

Figure 12. NMR spectrum of anions (26), (27), and (28).

49

Figure 13. NMR spectrum of 2,6-dimethy 1-2,5-hexadiene.


50


1 r ~i~;—

Figure 16. NMB. spectrum of 1,4-octadiene.

§-2-

s-f-n

51


Figure 18. NMR spectrum of isopropy1-1,4-pentadiene.

52


Figure 20. NMR spectrum of anions (35) and (36)

53

Figure 21. NMR spectrum of 2-methy1-1,4-pentadiene.


54

Figure 23. NMR spectrum of 2,4-dimethy 1-1,4-pentadiene.


55

A ,

Figure 25. NMR spectrum of 3-methyl-1,4-pentadiene.


56

Figure

Figure

Chemical Shifts (T)

Ha

Hb

He

7.00

3.80

5.90


Jab 12.0

Jbc 11.0

7. NMR parameters for pentadienyllithium at 45°.

CH_ f

Chemical Shifts (T)

Ha 7.38 He 5.79

Hb 3.70 Ilf 8.40

He 5.78

Hd 4.10


Jab 12.0 Jdf 6.0

Jbc 12.0

Jed 12.0

Jde 14.0

8. NMR parameters for anion (24) at 50°.

Figure

Figure

C H f

Chemical Shifts ( T ) Coupling Constants (Hz)

Ha 7.22 He 6.18 Jab 12.0 Jef 6.0

Hb 3.74 Hf 8.40 Jbc 12.0

He 6.10 Jed 11.0

Hd 4.10 Jde 11.0


CH„f

CrLe

Chemical Shifts (T)

Ha 7.78 He 8.40

Hb 3.90 Hf 8.50

He 6.441

Hd 4.36


Jab 12.0

Jbc 12.0

Jed 10.0


58

CH_b

CH.f

Chemical Shifts (7~)

Ha 7.26 He 5.90

Hb 8.50 Hf 8.50

He 6.51

Hd 4.05


Jed 10.0

Jde 14.0

Jef 6.0


HdHa He

Ha He

Chemical Shifts (7*) Coupling Constants (Hz)

Ha 7.50 H e -6.4 Jed 12.5

Hb 8.50 Hf 8.50 Jde 11.0

He 6.]6 Jef 6.0

Hd 4.04


59

CH. a H,c CH

HdCH h CH

Chemical Shifts ( T ) Coupling Constants (Hz)

Ha 8.60 Jed 11.0

Hb 8.40

He 4.34

Hd 6.90


CH3b

Chemical Shifts (T)

Ha 7.20 He 5.78

Hb -8.6 Hf 7.78

He 6.44 Hg ~9 .1

Hd 3.95


Jed 10.0

Jde 15.0

Jef 6.0

Jfg 6.0


CH38Hf X H 38

Chemical Shifts (T)

Ha 7.52 He 6.37 Jed 12.0

Hb ~8.6 Hf 7.78 Jde 11.0

He 6.10 Hg~9.1 Jef 6.0

' Hd 3.96 Jfg 6.0


Hb Hd HfHa JL

r ’ ' Mr '■Ha He

Chemical Shifts (7*) Coupling Constants (Hz)

Ha 7.60 He 5.96 Jab 12.0 Jef 6.0

Hb 3.88 Hf 8.20

He 6.20

Hd 4.26

Jbe 12.0

Jed 10.0

Jde 14,0


Chemical Shifts (T) Coupling; Constants (Hz)

Ha 7.42 He 5.80 Jab 12.0 Jef 6.0

Hb 3.82 Hf 7.90 Jbc 12.0

He 6.00 Hg 8.30 Jed 10.0

Hd 4.10 Jde 14.0

Fogure 37. NMR parameters for anion (33) at 40°.

Hb Hd

Ha HeCH g Hf 'CH3g

Chemical Shifts (T)

Ha 7.60 He

Hb 3.82 Hf 7.90

He 6.00 Hg 8.30

Hd 4.20


Jab 12.0 Jef 6.0

Jbc 12.0

Jed 10,0

Jde ^11


62

CH_b

Hf CH

Chemical Shifts (T)

Ha 7.22 He 5.80

Hb 8.4 Hf 8.02

He 6.54

Hd 4.02


Jed 10.0

Jde 14.0

Jef 6.0


CH hHd

Ha HeHa He Hf

Hf CH3

Chemical Shifts (T)

Ha 7.41 He ~ 6.6

Hb~8.4 Hf 8.02

He 6.21

Hd 4.00


Jed 10.0

Jde 9.0

Jef 6.0


63

CH.dHb

Ha HeHa He He

Chemical Shifts (f) Coupling Constants (Hz)

Ha 6.90 He 6.70 Jab 13.0

Hb 3.76 Jbc 10.0

He 6.20

Hd 8.30


HaHHeHa


Ha 6.83 None

Hb 8.40

He 6.80


64

HbHa

HaCH3

Chemical Shifts (T)

Ha 7.38

Hb 3.98


Jab 12.4


2 and 4 in pentadieny1littiium absorb in the normal range of olefinic

protons, but the hydrogens attached to carbons 1, 3, and 5 absorb in an

abnormally high range® Since theoretical calculations (Brickstock and

Pople 1954) predict higher electron density on carbons 1, 3, and 5 in pentadieny1lithium, it was assumed that higher field absorption indi

cated higher electron density* This is further illustrated by the ob

servation that the chemical shifts of the protons attached to carbons

bearing negative charge decrease as the electron density decreases in

the series allyl (end protons, T 8.0) (West et al* 1968), pentadienyl

(end, IT 7*1; central, T 5.9.) (Bates et al* 1967b), heptatrienyl (end,

T 6*7; internal, T 5 *5) (Bates et al* 1969). It was also observed that

primary hydrogens attached to carbons 1 and 5 absorb at higher field

than the secondary proton on carbon 3, which is reasonable since pri

mary carbanions are more stable than secondary carbanions and therefore

one might expect more negative charge at primary sites in such a hybrid

carbanion*

It is interesting to note the effect that added substituents2have on the chemical shifts of the protons attached to the sp carbons*

When, an alkyl group is placed on carbon 1, the hydrogens attached to

carbons 3 and 5 are in general shifted upfield, while the hydrogen on

carbon 1 is shifted downfield* If two methyl groups are placed on

carbon 1, the primary hydrogens are shifted further upfield. Placing

of two methyl groups on both carbons 1 and 5 shifts the secondary hy

drogen on carbon 3 up into the range where primary hydrogens absorb.

These observations seem to correlate with the relationship between

66

chemical shift and electron density since it would be expected that the

primary carbon in a 102030 anion would possess more negative charge

than in a 10202° anion and this latter anion would be similarly related

to a 102°10 aniono Also9 when one or two alkyl groups are placed on

carbons 1 and/or 5$ more negative charge would be expected on carbon 3,

thus shifting this hydrogen upfield. Placing of a methyl group on

carbon 3 causes more electron density to be shifted to carbons 1 and 5

and thus the hydrogens attached to these carbons are shifted upfield*

The chemical shift changes encountered when methyl groups are attached

to the 2 and/or 4 carbons may be explained by assuming that the methyl2groups twist the anion so that the sp carbons do not lie in one plane0

In the case of the 2-methyIpentadienyllithium* this twisting occurs at

carbon 2 which produces more double bond character in the bond,

and therefore more electron density on carbons 3 and 5* For example,

the hydrogens on carbons 1, 3, and 5 absorb at 7 6*70, T* 6*20, and

T 6 <,90, respectively* In the case of 2,4-dime thy Ipentadienyllithium,

this twisting produces more double bond character between and

C. _ and therefore concentrates more electron density on carbon 3*4-5This assumption is supported by the fact that the hydrogens attached to

carbons 1 and 3 absorb at 'T 6*83 and T 6*80, respectively*

Rotation in Anions

When a W~shaped pentadienyl anion contains an alkyl group on

the terminal carbon, cis- and trans-conformations can exist (40)* From

the nmr spectra of the terminally substituted anions investigated in

this study, it was apparent that.more than one anion was present in

67

(40)

solution and, from the coupling constants between the hydrogens at

tached to carbons 1 and 2, it was clear that both the cis- and trans-I

anions were present at room temperature. In all cases investigated

the nmr spectra indicated that the trans-isomer was present in higher

concentrations than the cis-isomer (Table 8), even upon heating to

100°. This indicates that the trans-isomer is thermodynamically more

stable, contrary to reports on allylie anions (Bank, Schriesheim, and

Rowe 1965; Bank 1965) where the cis-isomer was stated on the basis of

indirect evidence to be more stable. In the current study it was found

that when n-butyllithium is reacted with 1,3-pentadiene the allyl anion

(41) produced by addition is mostly in the trans-form (>907o). It was

R

(41)

hoped that if the anion from cis- or trans-114-hexadiene was prepared

and followed immediately by nmr, the presence of the pure cis- or

trans-anion could be observed and a rate of isomerization could be ob

tained. When this was done the nmr spectra at 35° showed that the

68

Table 8. Equilibrium concentrations of cis- and trans-anions.

Anion /<> Cis /0 Trans

(24,25)

(32)

(33,34)

(27,28)

(35,36)

45 55

46 54

28 72

40 60

35 65

25 75

(30,31)

69equilibration had already taken place faster than could be measured by

the instrument. Apparently the isomerization is fast (AG*<21 kcal/mole;

tL = 1800 sec) at that temperature, but slower than the nmr measurement

(AG*> 18 kcal/mole).

Since it was possible to heat these substituted anions to 100°

and still observe both cis- and trans-anions, it was apparent that the

rotation about the bond was quite slow. Bates et al. (1967b) have

investigated the rotation barriers in pentadienyllithium. They ob

served that above 40° the terminal hydrogens are equivalent and appear

as a doublet in the nmr spectrum, but at 15° they are nonequivalent and

appear as two separate doublets differing in chemical shifts and coupling

constants. This shows that at temperatures above 40° rapid rotation

about the C. bond is taking place, but at 15° this rotation is slower 1- /than the nmr measurement. It is possible to calculate the rate constant

for the averaging process at the nmr coalescence temperature using the

relation 42 (Pople, Schneider, and Bernstein 1959), where k^ is the rate

_1_ = a \J2

k2 " OT(Va - V

(42)

constant, (*L - V^) is the chemical shift difference in Hz at maximum

peak separation, and a is the initial concentration of anion. This

equation is based on the assumption that a second order reaction is in

volved in the rotation. From this rate constant, the barrier to

70rotation can be calculated by employing the Eyring equation (43) (Jen

sen et al. 1962). The rotation barriers for the anions investigated in

this present study are given in Table 9.

-AG*. kT RTk2 = h " e

(43)

In the discussion of these rotations, use will be made of the

illustration shown below (44). In all cases the R groups are hydrogens

(44)

unless otherwise stated. If R^ is CH^-, (CH^) CH-, or

CH^CH^- and R^ is CH^- or H-, the barrier to rotation about is

greatly increased (>18 kcal/mole) when compared to pentadienyHithium

(16 kcal/mole), while the barrier about decreases. If R^ and R^

are CH^-, the barrier about is somewhat lower yet. If R^ is CH^-,

the barrier to rotation about the Cn _ bond is also lower than in the1-2unsubstituted case. The barrier about the bond is highest when R^

and R^ are CH^-. The rotations about the inner bonds were rapid in

most cases even at -60°.

71

Table 9. Rotation barriers in pentadieny11ithiums.

Cl-2 C4-5Anion Tca AG* Tca >

°C kcal/mole °C kcal/mole

(23)4 2

45 16.2 45 16.2

(24,25) >100 >18.8 14.0

(32) >100 14.0

(33,34) >100 -3 13.5

(27) >100 >18.3 -10 13.5

(28) >100 >18.3 14.2

Table 9.--Continued 72

(35) ^ >100 -12 13.7

(36) >100 20

(30,31) >100 >18.3• h

(26) >100 >19.0 -15 12.9

(29) >100 >19.1 >100 >19.1

(37) 15 15.3 5 14.4

(38) 63 18.2 63 18.2

(39) -7.5 14.0 -7.5 14.0

a. Coalescence temperature.

73It was also observed that the rotation barrier about C. was4-5

higher for the cis-anion than for the trans-anion for the case when

or is CH^- or CH^CH^- and R^ is CH^-.

The simplest mechanism which accounts for the observed rota

tions is the one proposed by Bates, Gosselink, and Kaczynski (1967b).

This mechanism involves the collision between the lithium cation and

the carbanion to form a momentary covalent bond for a long enough

period of time to permit rotation about the single bonds produced. A

similar mechanism was proposed by Grovenstein and others (1966) for ro

tation in allyl carbanions. Since a covalent bond between lithium and

carbon 3 allows rotation about inner bonds and a covalent bond to

carbon 1 or 5 allows rotation about inner and outer bonds [(45) and

(46)], the barrier to rotation about internal bonds would be expected

to be lower than for outer bonds.

Li(45) (46)

When R^ is an alkyl group, more negative charge is expected at

Cg. (Birch, Shoukry, and Stansfield 1961) than at C. , so that more col

lisions will take place at the primary position and lower the barrier

to rotation about the C.‘ _ bond when compared to the unsubstituted4-5case. At the same time, the number of collisions at is decreased

and the rotation barrier about the bond is increased. If R^ and

74R are both alkyl groups9 the collisions at are further increased

and the rotation is even faster. When is an alkyl group, more col

lisions are .expected at and and this lowers the barrier to rota

tion about the terminal bonds 0 If and R are both CH -=, the rotation

barrier about the bond seems to be abnormally high, but is reason-

.able if the anion is assumed to be twisted, out of the plane causing

more double bond character between C1 and C. _01" I 4-5Further evidence for this mechanism was afforded by the results

of Sandel et al» (1968) when they observed that the rotation barriers

for phenylallyllithium increased in general in going from lithium to

potassium as the cation (see Introduction to Part II)„ This would be

expected if the above collision mechanism is occurring, since as the

size of the cation increases the desirability for the formation of the

momentary covalent bond decreases. Although an alternate mechanism in

volving rotation in the anion itself was proposed by the authors, the

above results seem to support the collision mechanism, ,

To obtain additional evidence for the mechanism involved in ro

tation, dilution experiments were performed. Pentadienyllithium was

prepared in the usual manner and an nmr spectrum was taken each time

the anion was diluted with dry THF, The upfield protons at 35° ap

peared as a broadened singlet at first, but changed to two doublets

(J = 16 and J =9) as 0,5 ml THF (total THF = 0,7 ml) was added. The

spectrum at the end of the experiment was characteristic of penta-

dienyllithium at less than IS0, The dilution increased the rotation

barrier about carbon-carbon bonds. This result would be expected with

75the collision mechanism^ since cation-anion collisions at high dilu

tion would be less probable$, but would not be expected if rotation was

taking place in the anion itself* These experiments show that the ro

tation is concentration dependent, but do not show conclusively that a

second order reaction is involved *

Sigmatropic Rearrangements of Pentadienyl Anions

Woodward and Hoffmann (1965) reported on the selection rules

for "sigmatropic" reactions, which they defined in the following way:

l!A sigmatropic change of order [i,j] is the migration of a CT-bond,

flanked by one or more TT~electron systems, to a new position whose

termini are i-1 and j-atoms removed from the original bonded loci, in

an uncatalyzed intramolecular process" (p* 2511)* It was stated that

orbital symmetry relationships must play a part in the course of these

transformations»

There are two possible ways in which hydrogen may be trans

ferred from to 0,- in the following example (47),

■R0CrCH-CH=CH-CHR* ' R0CH-CH=CH-CH=CR>z z z z(47)

If the hydrogen is associated at all times, with the same face of the

TT-system, the transformation is termed suprafacial, but if the hydrogen

is passed from the top of one carbon terminus to the bottom of another,

the transformation is called antarafacial* In considering example 47,

if the transition state is composed of a hydrogen atom and a radical

76containing five electrons, the highest occupied orbital in the system

possesses the symmetry illustrated below (48). Therefore, the [1,5]

transformation could take place in a suprafacial manner.

( 4 8 )

In considering the [1,6] shift in the pentadienyl carbanions,

the orbital used would look like 49, and an antarafacial transforma

tion would be required.

(49)

This type of transformation in carbanions was encountered in

the investigation presented in this dissertation as shown in Figure 44.

In the case of 26, the transformation took place at 40°, but 29 and

33 or 34 required heating to 90° even though both anions could be de

tected at 40°. The theory of Woodward and Hoffmann(1965) predicts that

the hydrogen shifts must take place in an antarafacial manner. In

order for this to occur, the carbanion must exist for a short period

of time in a helical all-cis form. This form does distort the

TT-systern of the carbanion somewhat, but it has been shown by Bates

77

H H40°

H H H

(26) 48% (27,28) 52%

H H

(29) 107<

90'

CH CH

CH

(30,31) 90%

(33,34) 107

90'CH CH3

CH3CH

CH

(35,36) 90%

Figure 44. Sigmatropic rearrangements of anions.

78and McCombs (1969) that pentadienyl carbanions can exist in a distorted

U-shape* Although the nmr showed the existence of only the W-shaped

carbanion, the distorted U-shaped carbanion must also be of low energy

since the transformations did take placee

Conclusions

In this part of the dissertation supporting evidence has been

obtained for a mechanism for rotation involving momentary formation of

covalent carbon-lithium bonds0 In many cases, numerical values for

rotation barriers were obtained; in others, only minimum values for

many of the rotation barriers could be calculated* It might be possi^

ble to obtain actual values for these barriers by preparing the anions

in a higher boiling solvent*

In some of the anions studied, a new positional isomerization

reaction possibly involving a 1,6-sigmatropic proton shift is observed*

Determination of whether this reaction is inter- or intramolecular is

necessary before it can be stated that these are .1,6-sigmatropic

shifts*

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Documents

I. Cleavage of tetrahydrofurans in n-butyllithium; II. Rotation … · 2020. 4. 2. · of n-butyllithium with various tetrahydrofurans0 A news high yield preparation of lithium enolates