Additions to Metal-Alkene and -Alkyne ComplexesRecal that alkenes, alkynes and other π-systems can be excellent ligands for transition metals. As a

consequence of this binding, the nature of the π-system changes from weakly nucleophilic to electrophilic.

+M+

+ –

– C

C

filled metald orbital

vacantd orbital

+

– +

–

vacant C=Cπ* orbital

++

––

filled C=Cπ-bond asσ-donor

The addition of the nucleophile can be external or internal.

LnM +

LnMNu

Nu

LnMNu

trans-addition

(external)

LnMNu

(external)

LnM

cis-additionNu

The resulting σ-alkyl or σ-alkenyl complexes can proceed to do other reactions.

A lot of very rich chemistry here. We will focus our attention on reactions promoted by Pd(II) and Au(I).

Attack on ligand favored by: • saturated metal center • π-accepting ligands • electron-poor metal centers • cationic complexes • soft nucleophiles

Palladium (II)-Catalyzed AdditionsPdCl2 and Pd(OAC)2 are commonly used. Strong donor ligands (phosphines) tend to shut down reactivity.

Weaker donor ligands (pyridines) can be used. Acceptor ligands (nitriles) also good.

R PdL2X2

PdL

X

X

R + Nuc

– X

trans-attack at most substituted end

PdX

L

L

NucR

π-alkene Pd(II) σ-alkyl Pd(II)

HB.H.E. R

+ HCl + Pd(0)Nuc

Z

H

ZPd

XL

Nuc

R

R M

PdL

L

R

NucRH

CPd

L X

CO

O

Nuc

RH Nuc

RH

H2 orformate

H+ Pd(0)

B.H.E. R.E. R.E.

All transformations involving theσ-alkyl palladium intermediate will eventually generate Pd(0).Either stoichiometric amounts

of metal are needed or a reoxidant must be present.

Pd(0)Pd(0)Pd(0)

Stoichiometric Oxidants for Generating Pd(II)Several stoichiometric reoxidant systems have been developed for convering Pd(0) back to Pd(II). There

are advantages/disadvantages with each. Choice determined by what else in going on the system and the stability ofstarting material/products toward the oxidant.

CuCl2 or CuCl2 w/ O2: likely involves sequential SET reactions. Catalytic in Cu if O2 (1 atm) is used.

Pd(0) + 2 CuCl2 PdCl2 + 2 CuCl

2 CuCl + 2 HCl + 1/2 O2 2 CuCl2 + H2O

Benzoquinone (BQ): Very mild and compatible with lots of functional groups. Stoichiometric organic impurity that must be removed.

O

O Pd(0)

HX

OH

O Pd X

OH

OXPd

HX

OH

HO

+ PdX2

O2 (1 atm): If the reaction is carried out in DMSO or with pyridine ligand, then O2 can be used by itself.

(pyr)2PdO2

OO

(pyr)2Pd2 HX

(pyr)2PdX2 + H2O2

Wacker OxidationOne of the first palladium-catalyzed reactions. Discovered by the process group at Wacker Chemie

(Angew. Chem. Int Ed. Engl. 1962, 1, 80). Orginially developed to convert ethylene into acetaldehyde.Has since become a general way to convert a monosubstituted olefin into a methyl ketone.

R

cat. PdCl2cat. CuCl2 (or Cu(OAc)2

O2 (1 atm)

DMF, H2OR Me

O

OOMe

HOPG

O

BnO OOMe

HOPG

BnOOOMe

HOPG

O

BnO

PdCl2, H2O

DMF, 45 ºC60%

O

O

O

MeMe CO2Me

O

MeMe CO2Me

O

PdCl2, CuCl2

O2, H2O, DMF65%

Me

Wacker OxidationInternal olefins are typically much slower to react

OAcPdCl2, CuCl2

H2O, DMF70–83%

OAc

O

In some cases a neighboring group, can alter the regioselectivity and form an aldehdye

MPMO OO

O

PdCl2, CuCl2

O2, H2O, DMF95%

MPMO OO

O

CHO

MPMO OHOH

PdCl2, CuCl2

O2, H2O, DMF93%

MPMO OHOH

O

Wacker-Type CyclizationsTethered nucleophiles (typically O and N) can be used to form heterocycles. Both terminal and internal

olefins work well. Can be coupled with other processes.

5 mol% Pd(OAc)2

DMSO, O295%HO O

HO2C

R

85% ee

OO

R

86% ee

PdCl2CuCl2, O2

84%NHTs

Pd(OAc)2, pyridineO2 (1 atm), xylene

80 ºC, 87%NTs

OH

O

Pd(MeCN)(BF4)2chiral ligand, BQ

MeOH, 90%

97% eeN

OO

HOBz

HHN

OO

HOBz

HO

PdCl2(MeCN)2(20 mol%)

77%

Note catalysis without oxidant

Wacker-Type Cascades

HO OBz

Pd(O2CCF3)2chiral ligand

CH2Cl2, BQ, 0 ºC89%, 82% ee O

H

OBz

Ph

OH

OH

OHPdCl2, CuCl2, CO

NaOAc, AcOH90% O

O O

Ph

HO

MeO

MeMe

Me

OH

MeO

MeMe

Me

OCO2Me

Pd(O2CCF3)2chiral ligand

CH2Cl2, BQ3.5 days

84%, 96% ee

CO2Me

Enol Ether Substrates (Saegusa Oxidation)

LDATBSCl

THF, HMPA

O

PivO

OTBS

PivO

Pd(OAc)2O2

DMSO74%

O

PivO

Useful C–C bond formations can be accomplished with silyl enol ether nucleophiles

More commonly, silyl enol ethers are oxidized to enones. Originally used stoichiometric amounts of Pdbecause turnover was not observed with BQ. Catalysis can be acheived with O2 and DMSO.

O

Me

MeOTES EtAlCl2

Toluene

O

Me

Me

HOTES

O

Me

Me

O

Pd(OAc)2

DMSO64%

H

O O

OTMS

O O

OTMS10 mol% Pd(OAc)2

O2 (1 atm)

DMSO, rt72 hrs

Additions to Alkynes

3 mol%PdCl2(PhCN)2

Alkynes are also excellent π-lignads for Pd(II). Nucleophilic addition produces an alkenyl Pd intermediate that is more stable than the alkyl Pd intermediates generted from alkenes (B.H.E. not a problem). This can

be intercepted by other processes or undergo protodemetallation (regenerates Pd(II)).

OH

C5H11 OC6H13 C6H13 OH

O+

H2O

OMe PdCl2(PhCN)2

H2O

O

O

50% 45%

92%

PdCl2(PhCN)2Et3N

THF, ΔOH

O

O O

100%

R

NHAc

NAc

R

PdCl2MeCN84-93%

Arylations of AlkynesHydroarylation of alkynes – likely invovles initial palladation of aromatic. Similar reactions with alkenes.

OMe

OMe

+ CO2EtPd(OAc)2, TFA

CH2Cl2, rt, 78%

OMe

OMe

CO2Et

+ CO2EtPd(OAc)2, AcOH

CH2Cl2, rt, 72% CO2EtPh

OMeO

Me

Ph

NHCOCF3

Ph

NCOCF3

Ph+ OTf

5 mol% Pd(PPh3)4Et3N

CH3CN, rt, 74%

Using Pd(II) formed from oxidative addition.

The Pauson-Khand ReactionCoupling of an alkyne, alkene, and CO to give a cyclopentenone. Both inter- and intramolecular variants are possible. Often use stoichiometric amounts of Co2(CO)8, but catalytic versions are known as well as

with other metals. Oftern requires high temperatures.

R2

R1+ R3

Co2(CO)8

solvent, heat

R2

R1

R3

O

Plausible mechanism:

– 2 CO Co(CO)3(OC)3Co

– CO

Co(CO)2(OC)3Co

RCo(OC)3Co

R

COCO

alkeneinsertion

+ CO

Co(CO)3Co(CO)3

R

alkeneinsertion

+ COCo(CO)3

Co(CO)3

R O

Co2(CO)8

O

R

(CO)3Co(CO)3Co

O

R

– Co2(CO)6

The Pauson-Khand Reaction

O O

O

CO2(CO)8, 4Å ms, PhMe

then Me3NO, H2O, PhMe60_70%

O

O

O

OOrg. Lett. 2005, 7, 1489.

amine oxides and other Lewis bases can be used as a promoter

Me

Me3SiH

H

OEt

O Co2(CO)8

then Et2AlCl82%

Me H

HO

CO2(CO)6

Me H

HO

O

H

NMO

85%

alkyne-cobalt complexes are quite stable and can be use as aprotecting group and to stabilize propargylic cations

OTIPSCO2(CO)6 S

O NMe2

+

O

TIPSOSAr

OH

J. Am. Chem. Soc. 1997, 119, 4353

NMO

MeCN62%

dr 97:3Chem. Eur. J. 2004, 10, 5443.