Organometallic Chemistry

5.44 An Introduction to Organometallic Chemistry

Note: Much of the handout and lecture material is taken, with permission, from “Organometallic Chemistry and its Application to Organic Synthesis,” a course given by E.N. Jacobsen (Harvard) and S.L. Buchwald (MIT). It is for your personal use. Please do not reproduce or distribute this material.

Professor Stephen L. Buchwald (18-490, [email protected]) Grader: Phill Milner ([email protected])

©S.L. Buchwald and E.N. Jacobsen, 2005-12, All rights reserved.

!Classes: 3/31, 4/7, 4/14, 4/15, 4/28, 5/5, !Hour Exam: April 28 in class (1.25 hours)-25% of grade!Presentation: May 5--25% of grade.!Final Exam: May 12, in class--50% of grade!There is no required textbook for this class.

Representative Text Books

Hartwig, Organotransition Metal Chemistry Crabtree, The Organometallic Chemistry of the Transition Metals Elsenbroich, Organometallics Spessard, Miessler, Organometallic Chemistry

ZrCp2

H2C

H2CCH2

Fe(CO)3Co

Organotransition Metal Chemistry

• Stabilization/Synthetic Utilization of Reactive Organic Structures

• Activation of Normally Unreactive Molecules

FEATURES:

Me Me

CHO+ CO/H2

(CO)8Co2

Me Me

CHO+

• Changes From Substrate-Controlled Outcome of Reactions

NBOC

F3C

OTBS H2/Pd-C

NBOC

F3C

OH(w/desilylation)

99:178%

NBOC

F3C

OH Crabtree

NBOC

F3C

OH

158:191%

Cy3PN Ir PF6

Crabtree's Catalyst

Cl CH3

OMe

Me

H

H

HTMS

TMS

O

TMS

TMS

O PhMe

O

Me

Ph

Features of Organotransition Metal Chemistry

• Extraordinary C-C Bond Constructions (relative to traditional organic chemistry)

+ MeMgBr

+CpCo(CO)2

– C2H4

Ni(PPh3)2Cl2

Mo(CHt-Bu)(NAr)[OCMe(CF3)2]2

Kumada Coupling

Ring Closing Metathesis

Alkyne Cyclotrimerization

I

N H

R

R"R'NR

R'

R"5% Pd(OAc)2/Ph3P+Larock Indole Synthesis

(first step is a Heck reaction)

(S)-BINAP

PPh2PPh2

Me NEt2

Me Me

Me

OH

Me Me

(S)-BINAP-Rh(I)

Me NEt2

Me Me

MeCHO

Me Me

Asymmetric Catalysis

(–)-menthol

*

Commercial Preparation of Menthol

NHCOCH3

CO2H

NPPh2

PPh2N

Ph Me

Ph Me

HN

CO2H

O

CO2HNH2

NHCOCH3

CO2H+ H2

(R,R)-PNNP-Rh(I) *

aspartame(R,R)-PNNP =

Commercial Preparation of Aspartame

M C M C M CM C

CM C C

What is Organometallic Chemistry?

• Chemistry of complexes containing transition metal-carbon bonds (Narrowest Definition)

alkyl alkenyl alkynylcarbene

(alkylidene)carbyne

(alkylidyne)

• Complexes that do chemistry involving intermediates containing transition metal-carbon bonds (Broader Definition -- Most Widely Accepted). This definition encompasses many of the catalytic processes that we are interested in.

(Ph3P)3RhCl (Wilkinson's catalyst-olefin hydrogenation and isomerization)

PdCl2/CuCl2 (Wacker catalyst)

• Any M-C Bond Containing Species, where M is more electropositive than carbon (Broadest Definition -- Applied by Organometallics)

Pd(PPh3)4 (Cross-couping and Heck Chemistry)

Rh2(OAc)4 (Carbenoid Insertion Chemistry)

SiR4 PR3 SnR4 AlR3

Transition Metals

La*

1 2

3 4 5 6 7 8 9 10 11 12

13 14

Transition Metal = Metal that can have a partially filled d shell

NOTE:in free metal 4s below 3din complexes 3d below 4s

EARLY LATE

e.g. Fe metal is 4s23d6

but Fe(CO)5 is 3d8

K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn

Rb Sr Y Zr Nb Mo Tc Ru Rh Pd Ag Cd

Cs Ba Hf Ta W Re Os Ir Pt Au Hg

Na

Be

Mg

B C

Al

Ga

In

Tl

Si

Ge

Sn

Pb

Li

The d Orbitals

x

z

dx2–y2 dz2 dxz dxy dyz

• Two orbitals with lobes on the axes and three orbitals with lobes between the axes

• Lobes oriented at 90°• Centrosymmetric

y

:COM

:PR3M:OEt2F3B

C–H

C–C

C–Cl

C–OR

σ bonding

M–H

M–alkyl

M–Cl

M–OR

vis

Covalent (may be more or less polarized): Dative:

Bonding in Organotransition Metal Complexes

vis

M Cl

M CO

M CR2

M CO

M Cl

M C

R2C CR2

halides, alkoxides, amidesare π donors

Covalent (again, may be more or less polarized):

δ bonding

Dative, metal as π acceptor:

CO, for example, is a π acceptor

(π acid)

Dative, ligand as π acceptor:

π bonding

vis

O

M X

H2C

H2CCH2

Fe(CO)3

Co

Bonding Representations

- All connections (covalent, dative) are symbolized by a simple line

- Formal charges not shown

- η2 or more bonding represented by a single line aimed toward the center of the array

• Oxidation states usually not shown

• Lone pairs on metal not shown

• Lines do not necessarily symbolize shared electron pairs:

PdPh3P

Cl PPh3

ClOC FeCO

CO

CO

CO

A B

The MO description of a covalent bond can be represented simply as:

ΔE

εM – εX

ΔE ∝orbital overlap

εM – εX

Ioni

zatio

n Po

tent

ial

A B

Small difference in electronegativity (εM – εX small)

Larger differences in electronegativity (εM – εX large)weaker covalent interactionstronger ionic interaction

stronger covalent bondsWhere the bond energy is related to ΔE, and:

A Primer on MO Theory

Electronegativity

K0.8

Ca1.0

Sc1.3

Ti1.5

V1.6

Cr1.6

Mn1.6

Fe1.8

Co1.9

Ni1.9

Cu1.9

Zn1.7

Rb0.8

Sr1.0

Y1.2

Zr1.3

Nb1.6

Mo2.1

Tc1.9

Ru2.2

Rh2.3

Pd2.2

Ag1.9

Cd1.7

Cs0.8

Ba0.9

La*1.1

Hf1.3

Ta1.5

W2.3

Re1.9

Os2.2

Ir2.2

Pt2.3

Au2.5

Hg2.0

Na0.9

Be1.6

Mg1.3

B2.0

C2.5

Al1.6

Ga1.8

In1.6

Tl1.6

Si1.9

Ge2.0

Sn1.8

Pb1.9

2 3 4 5 6 7 8 9 10 11 12 13 14

Li1.0

N3.0

O3.4

F4.0

P2.2

S2.6

Cl3.1

As2.2

Se2.5

Br2.9

Sb2.0

Te2.1

I2.6

Bi2.0

Po2.0

At2.2

15 16 17H2.2

Lanthanoids and Actinoids: 1.1 – 1.3

Pauling The Nature of the Chemical Bond, 3rd. Ed.; 1960Allred J. Inorg. Nucl. Chem. 1961, 17, 215

Covalent bonds in late organotransition metal complexes are relatively non-polar

Main Group More metallic (more electropositive)

Transition metals LESS metallic (more electronegative)

Some important trends:

Weaker bonds to carbon

STRONGER bonds to carbon

Electronegativity

Early metals Late metals More covalent bonds

M+ X- M-X

Group 3 4 5 6 7 8 9 10element Sc Ti V Cr Mn Fe Co NiPauling EN 1.3 1.5 1.6 1.6 1.6 1.8 1.9 1.9

cost $$$$$ $ $$ $ $ $ $ $Zr Nb Mo Tc Ru Rh Pd

1.3 1.6 2.1 1.9 2.2 2.3 2.2

$$ $$ $$$ $$$$$ $$$$ $$$$$ $$$$Hf Ta W Re Os Ir Pt

1.3 1.5 2.3 1.9 2.2 2.2 2.3

$$$ $$ $$$ $$$$ $$$$$ $$$$$ $$$$$

cost: $ Very cheap$$ cheap$$$ moderate$$$$ expensive$$$$$ very expensive

More Ionic More Covalent

Descriptive Periodic Table

M–X

Fe Ni

Zr Mo Ru Rh PdNb

Hf Ta

Tc

Re

Ti V Cr Mn Co

OsW Ir Pt

M+ X–

Periodic Trends in σ Bonding

More ionicMore oxophilic

Strongerbonds

Most electronegative

Most electropositive

All Hydrides Are Not Created Equal

O OCp2Zr

Cl

H

(CO)4Co–H

HCp2Zr

Cl+

Schwartz's Reagent

pKa < 1 in H2O 8.4 in CH3CNCatalyst for

oxo process

hydridic

acidic

Kinetic and Thermodynamic Acidity of M-H Complexes:Norton JACS 1987, 109, 3945.

M-C Bond Energies in Organotransition Metal Complexes

Bergman Polyhedron 1988, 7, 1429

M-C correlates with H-C

M

(CH3) > 1° > 2° > 3°

M

sp > sp2 > sp3

••

•

•

•

•

•

neopentyl

Pentyl

Vy

40 50 60 70 80 90

120

110

100

90

D(H

-X) i

n kc

al/m

ol

D(Ir-X) in kcal/mol

In general, if an equilibration mechanism exists (and it does), alkyl groups will isomerize to 1° product.

Cy

MeH

Ph

suggestedas due tosterichinderance

abnormally weak in this case

M–L

M L

:LM

:CM

:PR3M

O

:L

M

Neutral Dative Ligands

M

(or M–—P+R3)

(or M–—L+)

(or M–—CO+)

–Mδ+

δ+

or

MM–CO

M–PR3

Dewar-Chatt-Duncanson model

R2C CR2

C O

NOTE: CO and olefins do not form stable complexes with d0 TMs

Relatively weak σ donors (Lewis bases)can be excellent ligands for transition metal complexes

π Backbonding

d

C

C

π*

CO as σ donor CO as π acid

CC

d π*alkene as σ donoralkene as π acid

:CO :PR3

M MCO M M

ν (cm–1)

C O

2143 2164

More backbonding Weaker C–O

M C O

2060 1890 1730

M C O

1670 1500

π-Backbonding

Spectroscopic evidence:

Chemical evidence: pKa (in acetonitrile)

8.4

15.4

Reflects stability of –Co(CO)4 vs. –Co(CO)3PPh3

Ni(CO)4CO H3BCO

M

HCo(CO)4

HCo(CO)3PPh3

Cr(CO)44–Mn(CO)43–Fe(CO)42–Co(CO)4–

Complex is unstableOlefin rendered electrophilic

M M

Cp2(Me)Zr+

If M is electron withdrawing, backbonding is weak:

δ+

δ+

Olefin Complexes vs. Metallacyclopropanes

C

C

CC

d π*alkene as σ donoralkene as π acid

Zr(+4) has no d electrons

M M

Cp2Zr

If M is electron donating, backbonding is strong:

δ–

δ–Cp2Zr Complex is stableOlefin rendered nucleophilic

Zr(+2) has 2 d electrons(and Zr is more stable in higher OS)

The more electron-rich the metal, the more π-backbonding is seen. More metallacyclopropane character.

1

2

C-C bond length 1.438 Å1.337 1.536

135.8°

Ti

1.286 Å

*Cp

*Cp

120°180°

1.20 Å 1.34 Å

metallacyclopropene-much closer

ZrCp2

PMe3

nC4H9

ZrCp2

PMe3

nC4H9nC4H9

nC4H9

Phosphines

dπ dπ

PR3 as σ donor

d σ*

PR3

But very electron deficient phosphines can be excellent ligands for TM's

(e.g. PCl3, P(OR)3, etc.)

Structural evidence for phosphine as π acceptor:Pt

ClPh2P

P(CF3)2

Cl

2.32 Å

2.37 Å

2.24 Å

2.17 ÅPopular, but almost certainly incorrect interpretation:

PRR

R

More likely interpretation: P

R

RR

Orpen Chem. Comm. 1985, 1310

M

M

M

Cone Angle

2.28 Åθ

RR

R

P Ph2P PPh2

PF3

P(OMe)3

PMe3

P(t-Bu)3

PPh3

PCy3

PPhMe2H

Me

COPEt3, PPh2Me

θ

104

107

118

122

125

132

145

170

182

Cp

75

90

95

136

Tollman Chem. Rev. 1977, 77, 313

θ

Cone angles for non-phosphine ligands:

P(o-tol)3 194

*For a different view-"% Buried Volume: Nolan Chem. Commun. 2010, 46, 841

SPhos 240*

XPhos 256*

OMeMeO

PCy2

PCy2

iPriPr

iPr

:Cl–M+

:CH3–M+

:H–M+

::O2–M+2

M–Cl

M=O

M–H

M–CH3

M–CO :COM

Electron Counting

Method 1: The Dative Ligand Formalism

Assume all ligands are bound datively:

1. Disconnect all ligands according to the dative ligand formalism2. Place charges of the complex (if any) on the metal3. Count electrons remaining on the metal (gives d electron count)4. Add to electrons donated by the ligands

ADVANTAGE: Gives d electron count (and hence OS) directly

Common Ligands

bridging carbon monoxide -1 for each metal

2 for each metal

M M

O

metal-metal bond neutral 1 for each metal

M M

metal carbene neutral 2 M CH2

metal alkylidene -2 4 M CH2

M OR RO -1, 2 e-

M OR -1, 4 e-RO

M OR -1, 6 e-RO

Here π-bonding puts more electrondensity onto the metal. Note: an RO- group is isolectronic witha cyclopentadienyl group.

M

M

M

- -

π-allyl

-1 4 η3

σ-allyl η1-1 2

cyclopentadienyl (Cp)-

- -1 η56

X- ( - 1 c h arge) 2 e- 1 Cl-, Br-, I-, R- (e.g., CH3-), H-, Ar- RO-, RS-, R2N- (if no -bonding--see later) B: (Lewis Bases-neutral) 2 e- 1 :CO Carbon monoxide is probably the most important ligand in terms of industrial applications. R3P: Changing R can radically alter properties, e.g., M e3P:, small, basic, volatile liquid (b.p. ~35° C), very foul odor P h3P:, much larger, decreased basicity, white solid (m.p. 79-81° C) M e3P is a far superior donor of electron density to metals than is Ph3P

- -olefins

neutral

-2 η2

η2

- --2

2

alkynesneutral

η2

η2

4

M

M

2

M

4M

π-systems

1,3-dienes

M

M

neutral η44

neutral η22

M

MeMe

Me Me

Me

Me

Me

MeMe

Me

By placing substituents on the Cp ring, the properties of analogous complexes can be dramatically altered. The most common is the pentamethylcyclopentadienyl ligand usually denoted as Cp*.

-

-

The Cp* ligand has several effects. First, it is significantly more electron donating than the Cp ligand. It is also of much greater steric bulk. One manifestation of this added size, is the tendency for complexes to be monomeric and, hence, often significantly more reactive.

neutral η66

MnOC

OC CO

H

CO

CO

Example:

Step 1:

Mn+

OC:

OC: :CO

:H–

:CO

:COStep 2: N/A

Mn0 is d7

so Mn+ is d6

(6 unshared electrons)

Step 3:

Step 4: MnI (d6)H–5 x CO

62

10

18 e–(coordinatively saturated

complex)

MnOC

OC CO

H

CO

CO

Example:

Step 1:

MnOC:

OC: :CO

•H

:CO

:COStep 2: N/A

Mn0 is in the 7 th column,no charge

so metal e– count = 7

Step 3:

Step 4: MnH•5 x CO

71

10

18 e–(same answer)

Electron Counting Examples(Using Dative Ligand Formalism)

Pd(PPh3)4 ("tetrakis")

Pd0

Pd0 d10

8

18 e–

4 x PPh3

10 RhI d8

3 x PPh3

Cl–

16 e–

862

RhCl(PPh3)3 ("Wilkinson's catalyst")

Ph3P:

Ph3P:

:PPh3

:PPh3

Rh+

Ph3P:

Ph3P:

:PPh3

:Cl–

Electron Counting Examples(Using Dative Ligand Formalism)

acac–

VO

O

O

O

O

:O: O–

acac:4 e–, –1 charge

VO(acac)2 (an epoxidation catalyst)

::

acac–

VIV d1 2 x acacoxo

13 e–

The 18 e– "rule" often fails for early TM's

184

[Rh(COD)2]+ ("Schrock-Osborn complex")

RhI d8

2 x COD88

16 e–

For electron-counting purposes,charge on the complex is almost always

assumed to reside on the metal

V++++

O2–Rh+

M M M

M

CH2

M

CH2

M M

CH2

Hapticity

"Non-Innocent" Ligands

4 electron donor (–1) charge

η3-allyl

η1-allyl

2 electron donor (–1) charge

Pd+Me3P

Me3P

[(PMe3)2Pd(allyl)]+

–:CH2

PdII d8 2 x PMe3 η1-allyl

Pd+Me3P

Me3P

14 e–

–:CH2

Predict η3-allyl complex to be more stable. IT IS.

842

PdII d8 2 x PMe3 η3-allyl

16 e–

844

Pd2+

Me3P:

Me3P:Pd2+

Me3P:

Me3P:

Basic Reaction Types

1.!Oxidative-Addition LnM(a) + LnM(a+2)X

Y

Example: PdPh3P

Br PPh3Br

2.!Reductive-Elimination LnM(a) +LnM(a+2)X

YNote there is a decrease in formal oxidation state (-2) of the metal.

Example:

This is the most important means to form carbon-carbon bonds.

+PdPh3P

Ph3P

TMS

TMS

X-Y

+

This is the most important means to make carbon-metal bonds.

Note there is an increase in formal oxidation state (+2) of the metal.

(Ph3P)2Pd

X-Y

Review: Hartwig Inorg. Chem. 2007, 46, 1936

(Ph3P)2Pd

Basic Reaction Types-2

3. 4-Centered Reactions (σ-bond metathesis)

Note there is no change in formal oxidation state of the metal.

LnM(a) A +LnMa A

X Y+LnM(a) X

This is an important path for d0 (e.g., Zr(IV) ) metals to get substrates on and off the metal.

4. Ligand SubstitutionA) Simple Exchange-can be either associative or dissociative

B) Transmetallation

Example:

Stille ACIEE, 1986, 25, 508

Schwartz JACS 1975, 97, 3851review: Waterman OM 2013, 32, 7249

LnM + A (neutral, 2e- donor) ALn-1M + L

LnM X + LnM R + M'-XM'R e.g., CH3Li

nBu3Snor

PdPPh3

Ph PPh3

PdPPh3

Ph PPh3

Br+ nBu3Sn

X-Y A-Y

PdtBu3P

tBu3P

Cl CO2MePd

tBu3P Cl

PdtBu3P Cl

MeO2C

nBu3SnBr

t-Bu

Cp2Zr

D

HD

H

Cl

t-Bu

Br

D

HD

Ht-Bu

Cp2Zr

D

HD

H

Cl

BrBr2 Br

LnMR LnM

CR

CO O

LnMR

LnMR

carbon monoxide "insertions"

forward: insertion of olefins andalkynes into M-H and M-R'reverse: For R= H, β-hydrideelimination reactions

Basic Reaction Types-35.!Migratory Insertion ProcessesA) Small molecule insertions

CHNF, Ch 6

RhPh3PPh3P

CO

H CH3

RhPh3PPh3P CO

CH3

B) Oxidative-Cyclization Processes

LnM LnM LnM

This process is termed oxidative cyclization since two organic groups are coupled together and the metal is formally oxidized.

This is the primary means by which small molecules (e.g., CO, alkenes, alkynes) are incorporated into metal complexes and subsequently into organic products.

Cp2Zr NBn

TMS

Cp2Zr NBn

TMS

Cp2Zr NBn

TMSinsertion

Negishi J. Am. Chem. Soc. 1989, 111, 3336

Stille Comp. Org. Syn., Vol 4, Ch 4.5, p 913

a a+2ox state of M ox state of M insertion

a+2ox state of M

PdBr

L CO

AcN(H)CO/H2O Pd

Br

L

L

AcN(H)O

LL= Ph3P

cf. Tsuji, Palladium Reagents andCatalysts

LnM CH2

OOR'

R LnMO

R

OR'

LnM O H2COR'

R

LnMR

RLnM H2C

R

RLnM CH2

R

R

R'R'

R'

Basic Reaction Types-46.![2+2] Reactions

Grubbs, Pine Comp. Org. Syn., Vol 5, Ch 9.3, p 1115

NBn

CH3

NBn

H3C

MLn

NBn

CH3

MLn

Example:Grubbs, Miller, Fu Acc. Chem. Res. 1995, 25, 446-452, Grubbs Tetrahedron 1998, 54, 4413

7.!Activation of LigandsToward Attack by External Nucleophiles

LnM+ LnMNuc

MLnMLn

Nuc

X Nuc

LnM + LnM+ LnM +Nuc-Hegedus Comp. Org. Syn., Vol 4, Ch 3.1, p 551Tsuji Palladium Reagents and Catalysts, Wiley, 1995

+

+

+ Nuc- + Nuc-

X-

Petasis, JACS 1990, 112, 6392

Basic Reaction Types-5

8. Additional Elimination/Abstraction Processes

a) α-elimination Reaction LnMR

HLnM

R

H

Schrock JACS 1997, 119, 11876

b) α-abstraction Reaction LnMR

HLnM

R

R' Schrock Acc. Chem. Res. 1979, 12, 98R'H

Mo

N

NN

tBu

NMe3Si

Me3Si SiMe3Mo

N

NN

tBu

NMe3Si

Me3Si SiMe3

H

CpRu

Pearson TL 2005, 46, 3966NH

O HN

ON(H)Boc

HOOMe

OH

EtO

O

Cl

TBSO

PF6

NH

O HN

ON(H)Boc

OOMe

OH

EtO

O

TBSOCpRuPF6

88%

Mindiola ACIE 2014, 53, 10913N M

P

P

CH3CH3

OAr

M= Hf, Zr

full ligand is: NPiPr2iPr2P

hνN M

P

P

CH2

OAr

LnMR'

R

H LnM

R

H

R'

LnM

R

Basic Reaction Types-6We've already seen the β-hydride elimination reaction:

A related transformation is the β-abstraction reaction:

LnM

R

LnMR'

R

H

This process is a concerted process which accomplishes the same overall transformation. This can be important in cases in which β-hydride elimination would lead to an unstable intermediate.

Cp2ZrMe

Cp2ZrH

Cp2ZrH

Me

Cp2Zr

Buchwald Science 1993, 261, 1696

β-hydrideelimination Reductive

Elimination

R'H

β-abstraction

R'H

CH4CH4

d0

Cp2Zr

X

Y

Oxidative-Addition--Summary of Key Features

•!The reaction proceeds with a net increase in formal oxidation state of the metal center.

Favored in electronic rich (e.g., low valent) complexes.

Electron donating ligands (e.g., trialkylphosphines) increase the facility of oxidative addition.

Disfavored in electron deficient (e.g., high valent or cationic) complexes.

Electron withdrawing ligands (e.g., CO) decrease the facility of oxidative addition reactions.

•!The reactions are, in principle, reversible via reductive-elimination pathways.

•!Often ligand dissociation is required:- L Ln-1M18 e- complex

(Often unreactive)16 e- complex

L4M 18 e- complex - n L L2M or L1M 14 or 12 e- complex(e.g, M= Pd) Hartwig J. Am. Chem. Soc. 1995, 117, 5373

•!Oxidative-Addition is a generic descriptor providing no mechanistic information. Many mechanistic pathways fall under this term, including SN2, radical, 3-centered, ionic and bimetallic processes.

Crabtree, Ch 6, CHNF, Ch 5, Stille Review

LnM(a) + LnM(a+2)

LnM

X-Y

Oxidative-Addition Summary of Key FeaturesSN2-like Displacements-sp3 hybridized carbon:

LnM XRX

LnMX

R R Evidence for cationic intermediate: Puddephatt Organometallics 1987, 6, 2548

PdPPh3

Cl PPh3

Ph Cl

H DPh

D HPh

OHD H

RX: simple alkyls primary > secondary (mostly radical) >>> tertiary (radical)Until recently, not very synthetically useful--often see radical and reduction products.

X: I- > RSO3- ~ Br- > Cl-!!RSO3- best to minimize radical Pearson JACS 1982, 102, 1541

LnM

+ inversion(S)(R)

Stereochemical Evidence:

Other useful substrates (mechanistically ambiguous in many instances):

X Ar X ORX RX CHNF, Ch 5; Stille, Review; ACIEE 1986, 25, 508

Ir

Cl

OC

PPh3Ph3P CH3 I Ir

CH3

PPh3ClCOPh3P I

Ir

CH3

PPh3ClCOPh3P

I

trans product

(Ph3P)4Pd

IrCl

COPh3P

PPh3

+H

H

H

Ir

ClPPh3OCHPh3P

MLnH

H"Vaska's Complex"

rel rate: I > Br > Cl (>100 : 14.3 : 0.93)

MO analysis M

H

H

MH

H

σ p d σ*

Stable dihydrogen complexes first isolated in 1984:

W(CO)3(iPr3P)2 + H2

L

W

LOC

COOCH

H

0.84 Å

Kubas JACS 1984,106, 451 free H2 0.74 Å

X

Y

X

Y

R R LnM LnM

R

RR

LnM LnMLnM LnMR

Oxidative-Addition Summary of Key FeaturesConcerted 3-Centered Rxs-common for H2, R3SiH, reagents where groups are together (e.g., alkenes, alkynes)

X-Y

R R

R

XX

Radical Reactions: Both chain (most common) and cage seen:

Br

Br

PtBr

L

L PtBr

L

L

L4Pt-L

L3Pt +16e- e- transfer

L3Pt

Stille, Review,CHNF, Ch 5, Crabtree, Ch 6

LnM LnM-X LnM

Ir

Cl

CO

PPh3

Ph3P

+ CH3CH2-Br Ir

CH2CH3

PPh3ClCOPh3P

Br

via: CH3CH2• + IrCl(CO)L2 RIrII Cl(CO)L2

RIrII Cl(CO)L2 + RX R(X)IrIIICl(CO)L2 + R•

Evidence: • Observation of an induction period• Promotion by radical initiators• Observation of homocoupling products• Loss of stereochemistry with chiral electrophiles

Oxidative Addition-Radical Mechanisms

Note change in mechanism!from SN2 to radical upon!change from MeI to EtBr!as substrate.

Oxidative-Addition--Summary of Key Features-3Fairly recently Fu and subsequently Beller have shown that primary alkyl bromides and chlorides with β-hydrogens are viable substrates in Suzuki and Kumada type coupling processes, for example:

[(Cy3P)2Pd]Me Br(Cl)

Me(Cy3P)2Pd

Br(Cl)

Fu JACS 2001, 123, 10099, ACIEE 2002, 41, 1945Beller ACIE 2002, 41, 4056

Ph Br(tBu2(Me)P)2Pd

0 °C/Et2O

8

Fu JACS 2002, 124, 13662

PMetBu

tBuPd P tBu

Me

tBuBr

Ph

Fu Angew. Chem. Int. Ed. 2003, 42, 5749

Pd PP

Me

Me

Pd PP

similar steric environments for theapproach of R-X to Pd

R Br L Pd L+ L Pd LR

BrTHF, 0 oCL = P(t-Bu)2Me

Entry R Br krel ΔG

1

2

3

4

BrMe 7

Me

Me Br

MeBr

Me

Me

Me Br

1.0

0.19

0.054

<0.0001

19.5

20.3

21.0

>24.0

[kcal/mol]

ΔG [kcal/mol]LEntry

1234

PCy3

P(t-Bu)2Me

P(t-Bu)2Et

P(t-Bu)3

19.5 (0 oC)20.0 (0 oC)25.4 (60 oC)

>28.4 (60 oC)

Oxidative Addition of Alkyl Bromides to L2Pd(0)

Pd PP

Me

Me

Favoredconformermuch morehindered at Pd

Very sensitive to steric effects

Possible Mechanisms:

XMLn

XMLn

For LnNi + ArX: the top pathway is usually followed (electron transfer) For LnPd + ArI: the bottom pathway is followed

LnM +

LnM LnMXelectrontransfer

nucleophilicaromaticsubstitution

concerted

LnM(Ar)X

Oxidative-Addition--Summary of Key Features-4Oxidative-Addition at sp2 carbon: From the perspective of synthesis, this is the most important aspect of ox-add. Of these, most important systems are Ni(0) and especially Pd(0).

XR MR XL

L R

XM XL

LR

For ArX: Pd: Pd(PPh3)4 X= I > Br > OTf >> Cl (requires electron withdrawing subs--however, more modern systems allow for this to occur under reasonable conditions), however OTf > Br for PdCl2(PPh3)2 (Catalyst better able to coordinate to oxygen of triflate). Stille JACS 1987, 109, 5478Ni: X= I > Br> Cl > CN >> F! Cl is the most synthetically useful.Mechanistically, with Ni complexes, this is a very complex reaction.

Kumada P& A Chem. 1980, 52, 669; Stille ACIEE 1986, 25, 508;JACS 1984, 106, 4630

LnM + LnM +

CHNF, Ch 5, Tsuji Palladium Reagents and Catalysts, Wiley, 1995

ArX

ArX Ar•

Oxidative-Addition--Key Features-5Examining the reaction of (PPh3)4Pd + ArI:

(PPh3)3Pd + PPh3

(PPh3)2Pd + PPh3

Keq >> 1

Keq << 1

(PPh3)2Pd + ArI k

•rate= kexp [ArI] [Pd(0)]/[PPh3]; rate is inversely proportional to [PPh3].

•Hammett plot--ρ= 2.3; electron donating substitutents on aryl halide slow rate.

•ΔH‡ is the same in toluene or THF. This indicates that there is no solvent coordination involved in the oxidative addition step. It is most consistent with a mechanism in which there is "no charge development in the transition state," i.e. the concerted pathway.

For reactions of X I

•Kochi has previously shown that there are large variations (a factor of ~9) in the rates of oxidative addition of LnNi(0) to ArX with a change in solvent polarity. This is a reaction which is believed to proceed via the electron transfer pathway.•Amatore calculates that electron transfer from L2Pd to ArX is "more endergonic than from LnNi(0) to the same halide" by 35 kJ/mol (8.4 kcal/mol).

Amatore Organometallics, 1990, 9, 2276

(PPh3)4Pd

(PPh3)3Pd

(PPh3)2Pd(Ar)I

R R'

R''LnM

X

R R'

R''LnM

XX R''

R R'

LnM

Transformations of vinyl chlorides involving oxidative addition: Fu JACS, 2000, 122, 4020Stille, Review; CHNF, Ch 5; Stille ACIEE 1986, 25, 508

Oxidative-Addition--Vinylic SubstratesAlkenyl Halides and Triflates: Pd: I, OTf, Br commonly employed. Recent work indicates that Cl is viable: Ni: Cl and Br most studied, I also works.

Mechanistic Issues:

1)!Reactions proceed with retention of double bond geometry; inconsistent with free radical mechanisms.

2)!Ni(0) > Pd (0) > Pt (0), but Pd by far the most synthetically useful. Use of nickel catalysts can often lead to radical products.

3)!Reactions of vinyl bromides are faster than reactions with CH3I.

Postulated Mechanism:

Precomplexation

Br

ArBr

Ar

PdL2

ArPdL2 PdL2

PdL2

Ar

Br

MeAr

Me

PPh2

PPh2

Me

ArPdL2

<–30 °Cobserved by NMR– stable below –40 °C 1

1

"L2Pd"

stable below –20 °C

L2= DPPF =

(Corresponding I not observable)

observable at < 0 °C

Stepwise Transformation

Brown Inorg. Chem. Acta. 1994, 220, 249

CH3MgX

Fe

X

Y

LnM(a) +LnM(a+2)

Reductive-Elimination Summary

•!!Cis orientation of X and Y is required.

•!!Relatively favorable for electron deficient complexes. Relatively disfavored for electron !rich complexes; reductive-elimination leads to a complex in which the metal has a !reduced formal oxidation state.

•!!Rate enhanced by bulky ligands; reductive-elimination leads to a complex with decreased coordination number.

•!!Reductive elimination from a coordinatively saturated intermediate is favored as is formation of an electronically stable product (i.e., reaction to form an unstable molecule is disfavored).

•!!Reductive elimination has been shown to proceed with retention of !configuration at carbon.

PdCH3

Ph3P PPh3Ph

D H

CH3 Ph

D HPd

H3C

Ph3P PPh3

Ph

D HCHNF, Ch 5,Stille, Review

+

X-Y

(R)

L2Pd OTBS

O

H

H

D

D

OOTBS

H

H

D

D + L2Pd L2= DPPF

Woerpel JOC 1998, 63, 458

(Ph3P)2Pd

Review: Hartwig Inorg. Chem. 2007, 46, 1936

Rates of Reductive Eliminations: Bite Angle Dependence

review on bite angle effects: Dierkes, van Leeuwen, J. Chem. Soc. Dalton 1999, 1519

PPd

R

R'P

P

PdR

R'PR R'

PPh2

Ph2P

PdPh

MeMe

Ph2P

PPh2

PdPh

MeMe

bite angle +

bite angle = 89°

+ τ1/2=30 min @ 35 °C

bite angle = 97°

+ τ1/2~15 min @ 0 °C

larger

Consistent with DPPF's efficacy in cross-coupling reactions.

• Angle increases in the transition state for reductive elimination• Larger bite angle, faster rate of reductive elimination

Brown Inorg. Chim. Acta. 1994, 220, 249

P2Pd

(DPPP)Pd

Fe (DPPF)Pd

Electronic Effects on Reductive Elimination from Pd(II) Complexes

Hartwig Inorg. Chem. 2007, 46, 1936

PPh2

Pd

Ph2P

Ar RAr

R

DPPBz

40-100 °C

R

Me

CH2Ph

CH2C(O)Ph

CH2CF3

CH2CN

CF3

krel

>600

>250

31

1.7

1

no rxn

Ar =t-Bu

•More electron rich alkyl groups reductively eliminate more rapidly.

Ph

Ph


Halpern JACS 1978, 100, 2915

Ar3PPt

Ar3P Me

H

Ar

C6H4Cl

C6H5

C6H4Me

C6H4OMe

kobs(x104)

9.2

4.5

1.4

0.47

PhPh

Ar3PPt

Ar3PCH4

•reaction rate unaffected by addition of Ar3P. Therefore, reaction doesn't proceed by either an associative or a dissociative pathway.

•reaction shown to be intramolecular by crossover experiments.

Ph

PhAr3P

PtAr3P CD3

DPhPh

Ar3PPt

Ar3PCH4

Ar3PPt

Ar3P CH3

H+ + CD4

very little CH3D or CD3H was seen

More electron donating the ligandsare, the more slowly the rate of reductive elimination occurs. This isconsistent in the lowering of energy ofa transition state that is more electronrich than the ground state of the startingmaterial.

Relative Rates of Reductive Elimination HM

H

RM

H

RM

R> >

1b21a1

hybrid orbital

a1

b2

note: sp3 orbitals mustrotate toward each otherto reach transition state.

1b21a1

a1

b2

RM

R

HM

H

spherical symmetry of s orbitals makes red-elimin easier-better overlap in transition state

See: Albright, Burdett!and Whangbo:!Orbital Interactions in!Chemistry, pp 372-380.



Fe Pd

Ph2P

PPh2

Ph

N(tolyl)2

85 °C

1.5 h, 90%PhPN(tolyl)2

Fe Pd

Ph2P

PPh2

Ph

N(H)Ph

25 °C

1.5 h, 80%

Fe Pd

Ph2P

PPh2

Ph

NH

0 °C

1.5 h, 64%

HNPh2

MeMe

PhN(H)(i-Bu)

(pKa of HNPh2 = 25)

(pKa of H2NPh = 30)

(pKa of H2Ni-Bu ~ 41)

•More electron-rich N reductively eliminates faster



L2PdL2PdAr

NucAr Nuc

C P C S C N C O> > >

Relative Rates:

L1PdAr Nuc

L1PdAr

NucL2Pd

Ar

Nuc

L2PdAr Nuc

>

•Implies that reductive elimination from Pd(II) complexes faster with monodentate than with chelating ligands.

L2PdLPdNR2

Ar NR2

Ar H

reductive elimination

β-hydride elimination

X

Favored by: 1. X= EWG 2. More electron rich R 3. Larger ligands

Hartwig JACS 1996, 118, 3626

Cp*

RuMePh3P

Ph3P

XX

A B

4-Center Reactions Summary of Key Features

LnM(a) + A-BLnM(a)

+ B-X

• Requires open coordination site.

• No change in oxidation state of the metal.

• Cleavage of M-C bond proceeds with retention of configuration.

ALnM(a)

Jordan OM 2005, 24, 2688

NCp2Zr

Me Me

HH

PhSiH3 NCp2Zr

Me MeHHH2(Ph)Si H

Cp2ZrSi(Ph)H2NMeMe

Me

+

Review: Waterman OM 2013, 32, 7249Hartwig, JACS, 1994, 116, 1839

+O

H-BO

HBcat

Cp*

Ru Me

Ph3PPh3P

H Bcat

Cp*

RuHPh3P

Ph3P+ MeBcat

LnMR LnM

CR

CO Ocarbon

monoxide insertions

Migratory Insertion Reactions Basic Summary-CO

•!Although the reaction is usually referred to as a carbon monoxide insertion reaction, mechanistic studies have shown that it actually takes place by an alkyl migration pathway.

•!Requires cis orientation of R, CO.

•!Relative migratory aptitude:

CH3 CF3 H

This trend reflects relative metal-X bond strengths.

•!Proceeds with retention of configuration at migrating carbon.

LnM

sp3 carbon

> LnM

sp2 carbon

>> LnM = LnM

very rare

t-Bu

Fe(CO)2

D

H D

H

Cp

t-Bu D

H D

H

Fe

Cp PPh3O

COPh3P

THF

Whitesides JACS 1974, 96, 2814

LnMR

LnM

R

R R

R R

R

R R

R R

RR

R

R R

Migratory Insertion Reactions Basic Summary-Alkene/Alkyne

•!!Requires cis orientation of R, alkene.•!!Cis addition of LnM, R.•!Relative migratory aptitude: LnM-H >> LnM-CH3 (kinetic effect). In the best studied system to date, kHmig/kRmig ~107-108. Although the latter is the key step in Ziegler-Natta polymerization of olefins.

Brookhart JACS 1988, 110, 8719

forward: insertion of olefins andalkynes into M-H and M-R'reverse: For R= H, β-hydrideelimination reactions

•!!Relative rate of insertion:

>> > > >>> >

CHNF, Ch 6

RLnM

R'H LnM H

R'

R

H3C

H3C CH3

L2Pt H3C

L2Pt H3C

L2PtnBunBu

L2Pt H L2Pt H

L2Pt +

L2Pt +

L2Pt

Optimum transitionstate has Pt, H andthe 2 C's coplanar

Cf. Crabtree CHNF, Ch 6

best when H-C-C-Pt angle is 0 °

β-hydrideelimination

Migratory Insertion Reactions--Summary-β-Hydride Elimination

•!Requires open coordination site. Relatively slow for coordinatively saturated complexes. One manifestation of this can be seen in changing from simple phosphines to chelating bis-phosphines. This inhibits phosphine dissociation and keeps the complex coordinatively saturated.

•!Principle mode of decomposition for metal alkyls.

•!Important step in olefin isomerization.

•!Shows geometric effects; slower in metallacyclic compounds.

+ +

4

krel

1

1

10-4

LnM + H2 LnMH

HOxidative-AdditionLn+1MLigand-loss (exchange)

18 e-

L 16 e- 18 e-

Ln-1M

H

CH3

- C2H6

ReductiveElimination

0 0 +2

Ligand-loss (exchange)

-L

Ln-1MH

H

16 e-

+2Ln-1M

H

H+2Ligand-add (exchange)+2

16 e-

Insertion

Ligand-add (exchange)+L

LnM

H

CH3

+2

LnM16 e-

0

18 e-

Catalytic Cycles-1-Hydrogenation

James in Comp. Organometallic Chem., 1982, Vol 8, Ch 51, p 285, CHNF, Ch 10

HRh(CO)2L2

-CO

18 e-

HRh(CO)L2 16 e-

R

RhLL

H

CO

R

RRh(CO)L2

H3C Rh(CO)L2

R

RRh(CO)2L2

RRh(CO)L2

H

H

R CH3olefinhydrogenation

R

O

Rh(CO)L2

R

O

RhLL

H

CO

H

RCHO

RegiochemistryDetermining

Ligand loss(exchange)

Ligand add(exchange)

ox-add

insertion

red-elim

red-elim

ox-add

migratoryinsertion

migratoryinsertion

18 e-

16 e-

16 e-

18 e-

18 e-

18 e-

Catalytic Cycles-2-Hydroformylation

Stille Comp. Org. Syn., Vol 4, Ch 4.5, p 913

R Me

CHO

Iso+CO

+H2

+H2

Catalytic Cycles-3-Heck Aminocarbonylation of Aryl HalidesL/ Pd

solvent, Base (B:), CO+Ar-X

Ar N(R1)R2

OHN(R1)R2

L2Pd

+ Ar-Cl

L2PdX

O

Ar

+ CO

Ar N(R1)R2

O

HN(R1)R2Nucleophilic Attack or Reductive Elimination

B•HCl

B:

Cycle ACycle BL2Pd

Cl

ArL2Pd

N(R1)R2

O

Ar

Ar N(R1)R2

O

B•HCl

B:

L2PdH

Cl

OA

MILE

RERE

14

16

16

1616

Review: Barnard OM 2008, 27, 5402

Background Material for 5.44

The 18 Electron Rule

n d

n+1 s

n+1 p

n M–L bonding

9 – n non-bonding

Consider a complex MLn:

Ln

M

A stable electronic configuration is achieved if all bonding and non-bonding MO's are filled.

Mitchell, Parish J. Chem. Ed. 1969, 46, 811

ZrCp2 ZrCp2

Cp–

Cp–

Cp–

ZrII d2

2 x Cpη2-benzyne

Examples

16 e–

0124

Backbonding does not change e– count, but it does change formal oxidation state.

An example of why oxidation state is really only a formalismin organometallic chemistry (although often a useful one)

Cp–

2122

ZrIV d0

2 x Cpbenzene dianion

16 e–

Zr2+ Zr4+

M

L

L

L

L

L

L

Lax

M

Lax

Leq

Leq

Leq

Metal-Ligand Complex Geometries

L LL L

Six coordinate:

octahedral

cis

trans

Five coordinate:

trigonalbipyramidal

M

L

squarepyramidal

Four coordinate:

tetrahedral squareplanar

cis

trans

L

MLL

L ML

L

L

L

IrPh3P Cl

OC PPh3

ClPd

ClPd

ML X

R L

d8 Square Planar Complexes

All are stable, 16 e–complexes.Square planar geometries:

(Wilkinson's catalyst)

But Pd(PPh3)4 is tetrahedral (a d10 complex)

ClRh(PPh3)3 PdCl2(PR3)2

[Very] Simple MO Theory

Octahedral ML6: L

L L

L

Ligand-centered

eg

t2g

L

dz2

L

dx2-y2

dxz dyz dxy

zy

x

12 e-

6 e-

M

Δ

See Crabtree, Ch 1, 2

Δ is larger for: 1. 2nd and 3rd row TM's 2. "strong ligands"--e.g., CO (π-effects), Ph3P, H-

(more electron density, accentuates LF effects)

LM

L

L

L

z

LL

y

x

d6 octahedral

MO Diagram for an Octahedral Complex

dx2-y2, dz2

dxy, dyz, dxz

LM

L

L

L

x

zy

MO Diagram for Tetrahedral d8 Complex

dxy, dyz, dxz

dx2-y2, dz2

eg

t2g

eg

t2g

if π-Backbonding

eg

t2g

eg

t2g

if π-Donation

More tendency to be 18 e-

Δ Δ Δ Δ

Effect of π-Bonding on Orbital Energies

electron density is removed from the metal, lowering the energy of these orbitals (by mixing with the empty ligand π*)

interaction with filled ligand π orbitals, raises the energy of these orbital (electron-electron repulsion)

See Crabtree, pp17-19

L

ML L

L

x

zy

MO Diagram for Square Planar d8 Complex

dx2-y2

(sits on x-y axis)

dxy

(between x-y axis)

ligand centered

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