Cobalt Catalyzed Reactions

Keith Proinsias
20/12/2011

OVERVIEW

Introduction

OXO process

Cross coupling reactions using Grignard reagents

Cobalt coupling Michael addition reactions

Cobalt catalyzed Heck type reactions

Reductive cyclization and Heck type reactions

Cobalt catalyzed allylation of 1,3-dicarbonyl compounds

Coupling of alkenes and alkynes

Cobalt catalyzed syn-hydrophosphination of alkynes

Cobalt catalyzed C-N coupling

Cobalt catalyzed C-S coupling

INTRODUCTION

The oxidation state of cobalt in organocobalt compounds

ranges from -1 to +4.
The most common being -1, 0, +1 and +3.
Co(0) complexes consists of homoleptic carbonyl: Co2(CO)8
and Co4(CO)12.
Co2(CO)8 is used as a homogeneous catalyst in the
hydroformylation of alkenes.
It is thermally unstable, decomposing above 50oC to give
Co4(CO)12.

Solid
In Solution
Kamiya, S. Synthesis of organometallic compounds: A practical guide, John Wiley & Sons.

INTRODUCTION

Co(I) complexes contain -acid ligands: Cp, CO, RNC,

and PR3.
Co(I) complexes are usually five-coordinated and
trigonal bipyramidal.
In oxidative addition reactions give Co(III) in which one
ligand is eliminated.
Monocyclopentadienyl (Cp) complexes are one on the
most extensively studied cobalt complexes.
CoCpL2 (L= PPh3, CO) are capable of catalyzing the
cyclotrimerization of alkynes as well a variety of other
compounds to give other types of bonds.

Kamiya, S. Synthesis of organoetallic compounds: A practical guide, John Wiley & Sons.

INTRODUCTION

Kamiya, S. Synthesis of organoetallic compounds: A practical guide, John Wiley & Sons.

INTRODUCTION

Since the discovery of vitamin B12 coenzyme there has been

much work done on organocobalt (III) complexes with a
metal-carbon bond.

Kamiya, S. Synthesis of organoetallic compounds: A practical guide, John Wiley & Sons.

OXO PROCESS

OXO PROCESS
OXO process is the hydroformylation of alkenes (such as
propene) to make aldehydes.
This process is catalyzed by Rh or Co.

Kamiya, S. Synthesis of organoetallic compounds: A practical guide, John Wiley & Sons.

OXO PROCESS
Catalytic cycle:
-Complex formation.
Hydrometallation to produce an alkyl metal species.
Coordination of carbon monoxide followed by insertion.
Reductive cleavage with hydrogen to produce the metal-hydride
intermediate.

Kamiya, S. Synthesis of organoetallic compounds: A practical guide, John Wiley & Sons.

CROSS COUPLING

CROSS COUPLING
Cross-coupling reactions between an organometallic reagent and an
organic halide or triflate.
Reaction requires a transition metal catalyst. Pd is commonly used.

Mechanism
Oxidative addition of the halide to the initial palladium(0)complex to form a
palladium(II) species.
Transmetallation: the nucleophile is transferred from the organometallic
reagent to the palladium and the counter ion moves in the metal.
The new palladium(II) complex with two organic ligands undergoes reductive
elimination to give the coupled product

Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic chemistry, Oxford University Press, 2001

CROSS COUPLING
The halide partner must be chosen with care, as -hydride elimination
would decompose the first intermediate during the slow transmetallation
step.
The choice for is restricted to substituent's without -hydrogen atoms:
vinyl, allyl, benzyl, and polyfluoroalkyl halides,triflates, and phosphates have
all been coupled successfully.
The organometallic reagent can be based on magnesium, zinc, copper, tin,
silicon, zirconium, aluminium, or boron
The organic fragment can have a wide variety of structures as coupling is
faster than -hydride elimination.

Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic chemistry, Oxford University Press, 2001

COBALT CATALYZED
CROSS COUPLING USING
GRIGNARD REAGENTS

COBALT CATALYZED CROSS

COUPLING USING GRIGNARD
REAGENTS
The first cobalt catalyzed cross coupling reaction was described the
homocoupling reaction of Grignard reagents
In 1939 Gilamn and Lichtenwatler obtained almost quantitative yields
of diphenyl homocoupled product by treating aromatic Grignard reagents
with a stoichiometric amount of cobalt bromide.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Gilman, H.; Lichtenwalter, M. J. Am. Chem. Soc. 1939, 61, 957

COBALT CATALYZED CROSS

COUPLING USING GRIGNARD
REAGENTS
Kharasch continued these
homocoupling reactions by isolating
diphenyl compounds in good yields.
3 mol % of cobalt chloride required

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Kharasch, M. S.; Fuchs, C. F. J. Am. Chem. Soc. 1941, 63, 2316

COBALT CATALYZED CROSS

COUPLING USING GRIGNARD
RtheEAGENTS
In 1943 Kharasch reported
first alkenylation reaction between
Grignard reagents and vinyl halides catalyzed by cobalt chloride.
Catalytic amount of cobalt chloride (2.5 mol %).

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Kharasch, M. S.; Fuchs, C. F. J. Am. Chem. Soc. 1943, 65, 504

COBALT CATALYZED CROSS

COUPLING USING GRIGNARD
REAGENTS
This work to still ongoing.
Yoshikai recently reported a
quaternary catalytic system
consisting of CoBr2, P(3-ClC6H4)3,
tBuCH2MgBr, and pyridine
promotes hydroarylation of an
internal alkyne with an aromatic
imine through chelation-assisted
CH bond cleavage

Lee, P. S.; Fujita, T.; Yoshikai, N. J. Am. Chem. Soc. 2011, 133, 17283

COBALT CATALYZED CROSS

COUPLING USING GRIGNARD
REAGENTS
Alkenylation
From aromatic organomagnesium reagents
From vinylic Grignard reagents
From aryl halides and alkenyl acetates
Aryl-Aryl Cross coupling
From aromatic organometalic reagents
From two aromatic halides
Alkynylation
Benzylation of acetylenic Grignard reagents
Alkylationof acetylenic Grignard reagents
Alkenylation of acetylenic Grignard reagents
Csp3-Csp2 Cross-coupling
Allylation
Benzylation
Alkylation
Acylation
From organometallic compounds
Cobalt- mediated acylation of aryl bromides

COBALT-MEDIATED
MICHAEL ADDITION

COBALT-MEDIATED MICHAEL
ADDITION
Giese describes a diastereoselective conjugative addition using
Vitamin B12 as a catalyst and Zn as a reducing agent

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

COBALT-MEDIATED MICHAEL
ADDITION
Pfaltz developed the synthesis of C2symmetric bis-amides.
He found by this ligand in Michael
addition reactions high ee could be
obtained but with low yield.

Using similar ligands Cheng

reported the Michael addition of
malonates to chalcone derivatives
using cobalt complexes and Et2Zn
Good yield and moderate ee.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

End, N.; Macko, L; Zehnder, M.; Pfaltz, A. Chem. Eur. J. 1998, 4, 818
Chen, C.; Zhu, S. F.; Wu. X. Y.; Zhou, Q. L. Tetrahedron: Asymmetry 2006,
17, 2761

COBALT-MEDIATED MICHAEL
ADDITION
Bergman reported a one-pot,
direct C-H functionalizaion of
alkenes meditated by
[CpCo(NO)2].
A variety of Michael acceptors
can be used

Zhao, C.; Toste, F. D.; Bergman, R. G. J. Am. Chem. Soc. 2011,

133, 10787

COBALT-CATALYZED
HECK TYPE
REACTIONS

COBALT-CATALYZED HECK TYPE

REACTIONS
The Heck Reaction is a powerful tool in carbon-carbon bond formation

There are limitations regarding substrate choice, which are limited to

aryl, heteroaryl, vinylic and benzylic halides and triflates as the
presence of an sp3 carbon in the -position carrying a hydrogen rapidly
results in -hydride elimination.
Cobalt catalyzed Heck type reactions avoids this drawback.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Clayden, Greeves, Warren, Wothers, Organic chemistry, 1313

COBALT-CATALYZED HECK TYPE

REACTIONS
In 1991 Branchaud reported the first cobalt catalyzed Heck type reaction
between styrene and various alkyl halides.
Reaction was catalyzed using Cobaloxine (II) and requires daylight.
The use of 3o bromides fail.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

COBALT-CATALYZED HECK TYPE

REACTIONS
[A] CoCl2.dpph reacts with
Me3SiCH2MgCl.
[B] Monoelectronic transfer to the
alkyl halide forming a CoI species.
[C] CoI reacts with Me3SiCH2MgCl
forming an intermediate.
[D] Then reacts with the benzylic
radical forming the organocobalt [E].
[F] The Heck product is obtained from
[E] by -hydrogen elimination.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

COBALT-CATALYZED HECK TYPE

REACTIONS

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Ikeda, Y.; Yorimitsu, H.; Shinokubo, H,; Oshima, K. Adv, Synth. Catal. 2004, 346, 1631

REDUCTIVE
CYCLIZATION AND
HECK-TYPE
REACTIONS

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS

INTERMOLECULAR RADICAL CYCLIZATION

INTRAMOLECULAR RADICAL CYCLIZATION

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS

INTRAMOLECULAR RADICAL
CYCLIZATION
Radical mediated aryl-aryl
coupling
The first reported case was by
Tiecco in 1965
Methylmagnesium iodide was
used in a suspension of cobalt
chloride in an ethereal solution
affording phenanthrenein 75%
yield

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Tiecco, M. Chem. Commun. 1965, 555

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS
In 1982 Tada reported the
reductive cyclization of 2propargyloxyalkyl bromides in
the presence of cobaloxime.
Hoffmann applied this method
to the synthesis of various
heterocyclic compounds.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Okabe, M.; Abe, M.; Taba, M. J. Org. Chem. 1982, 47, 1775
Abe, M.; Taba M. J. Org. Chem. 1982, 47, 5382
Last, K.; Hoffmann, H. M. R. Synthesis1989, 901

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS
Pattenden reported the radical
cyclization of 2-allyloxyalkyl
bromides using Vitamin B12 or
cobaloxime (I)

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS

INTERMOLECULAR RADICAL CYCLIZATION
Typically this reaction is
catalyzed using Pd or Ni due
to the facile oxidative
addition of aryl halides to Pd
and
Ni(0) metal complexes..
Yamamoto shows the
addition of vinylpalladium
species to carbon
electrophiles such as a
carbonyl group
This was the first
palladium-catalyzed
nucleophilic cyclic
vinylpalladation of aryl
ketones
alkynes
to Reviews 2010, 110, 1435-1462
Cahiez, G.;with
Moyeux,
A. Chemical
produce
Quan, L. G.; Gevorgyan, V.; Yamamoto, Y. J. Am. Chem. Soc. 1999, 121, 3545
Indenols in good to high

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS
Cheng first reported that cobalt
phosphine complexes successfully
catalyse the reaction under mild
conditions to afford indenol derivatives
with excellent regioselectivity and in high
yields
The cobalt catalyzed system is more
efficient than the palladium and nickel
catalysts for this
carbocyclization reaction.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Chang, K. J.; Rayabarapu, D. K.; Cheng, C. H. Org. Lett. 2003, 5, 3963
Chang, K. J.; Rayabarapu, D. K.; Cheng, C. H. J. Org. Chem. 2004, 69, 4781

REDUCTIVE CYCLIZATION AND

HECK-TYPE REACTIONS

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Chang, K. J.; Rayabarapu, D. K.; Cheng, C. H. Org. Lett. 2003, 5, 3963
Chang, K. J.; Rayabarapu, D. K.; Cheng, C. H. J. Org. Chem. 2004, 69, 4781

COBALT CATALYZED
ALLYLATION OF
1,31,3-DICARBONYL
COMPOUNDS

COBALT CATALYZED ALLYLATION OF

1,31,3-DICARBONYL COMPOUNDS
Iqbal reported the allylation of 1,3-dicarbonyl compounds using a cobalt
catalyst.
Reactions were conducted under neutral conditions, compared to Pd
catalyzed reactions

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

COBALT CATALYZED ALLYLATION OF

1,31,3-DICARBONYL COMPOUNDS
Reactions can also be repeated with allylic alcohol.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

COUPLING OF
ALKENES AND
ALKYNES

COUPLING OF ALKENES AND

ALKYNES
Commonly copper mediated reactions are used for the preparation of
conjugated diynes.
In 2001 Kraff reported cobalt catalyzed dimerization of terminal alkynes.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Krafft, M. E.; Hirosawa, C.; Dalal, N,; Ramsey, C.; Stiegman, A. Tetrahedron Lett. 2001, 42, 7733

COUPLING OF ALKENES AND

ALKYNES
Cheng followed suit with the reductive dimerization of conjugated alkenes,
which were highly regio- and stereoselective.

dppe=1,2-Bis(diphenylphosphino)ethane

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Wang, C. C.; Lin, P. S.; Cheng, C. H. Tetrahedron Lett. 2004, 45, 6203
Chang, H. T.; Jayanth, T. T.; Wang, C. C.; Cheng, C. H. J. Am. Chem. Soc. 2007, 129, 12032

COBALT-CATALYZED
SYNHYDROPHOSPHINATION
OF ALKYNES

COBALT-CATALYZED SYNHYDROPHOSPHINATION OF
ALKYNES
Reaction traditionally with lanthanides, Pd or Ni
Stereoselectivity of these reactions depend on the nature of the substrate

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Mimeau, D.; Gaumont, A. C. J. Org. Chem. 2003, 68, 7016

COBALT-CATALYZED SYNHYDROPHOSPHINATION OF
ALKYNES
Oshima developed a cobalt catalyzed universal stereoselective
hydrophosphination reaction of alkynes with diphenylphosphine and
butyllithium giving mainly syn-addition product.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Ohmiya, H.; Yorimitsu, H.; Oshima, K. Angew. Chem. Int. Ed. 2005, 44, 2368

COBALT-CATALYZED SYNHYDROPHOSPHINATION OF
ALKYNES
Product can be used to perform Wittig reaction.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Ohmiya, H.; Yorimitsu, H.; Oshima, K. Angew. Chem. Int. Ed. 2005, 44, 2368

COBALT CATALYZED
C-N COUPLING

COBALT CATALYZED C-N

C
OUPLING
Cobalt-porphyrin catalyzed C-H amination has been extensively
examined by Cenini.
Reactions are limited to cyclohexane.
Substrates have been extended to benzylic C-H bonds.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Cenini, S.; Tollari, S.; Penoni, A.; Cereda, C. J. Mol. Catal. A. 1999, 135
Cenini, S.; Gallo, E.; Penoni, A.; Ragaini, F.; Tollari, S. Chem. Commun. 2000, 2265

COBALT CATALYZED C-N

COUPLING

Yamaguchi developed new

methodology to prepare N-aromaticcontaining tertiary amines that are
useful
building blocks for bioactive
molecules.
He was the first to use N-aromatic
2-chloro compounds for CN bondforming reactions.
Toma, G.; Yamaguchi, R. Eur. J. Org. Chem. 2010, 6404
Toma, G.; Fujita, K.; Yamaguchi, R. Eur. J. Org. Chem. 2009, 4586

COBALT-CATALYZED
C-S COUPLING

COBALT-CATALYZED C-S
C
OUPLING
Typically C-S coupling is conducted using Cu, Pd or Ni catalyst under
harsh conditions.

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Bates, C. G.; Gujadhur, R. K.; Venkatamaran, D. Org. Lett. 2002, 4,
3517

COBALT-CATALYZED C-S
COUPLING
Cobalt-catalyzed C-S coupling requires milder conditions.
Low catalytic loading

Cahiez, G.; Moyeux, A. Chemical Reviews 2010, 110, 1435-1462

Wong, Y. C.; Jayanth, T. T.; Cheng, C. H. Org. Lett. 2006, 8, 5613

CONCLUSION
Cobalt and its complexes can catalyze many many different
reactions including:
Cross-coupling reactions
Heck-type reactions
C-N coupling
C-S coupling
and many more

THANK YOU
FOR YOUR ATTENTION

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