1

CHAPTER-1

Cobalt(II)-Catalyzed Organic

Transformations

2

1.1. Introduction

Elements in the d-block of the periodic table (except Zn, Cd and Hg) are generally

called transition elements, and share some common characteristic properties, which are

listed below. They contain an incomplete d subshell.

They are often paramagnetic.

They have many different oxidation states.

They form complexes.

They are often good catalysts.

The last point concerning catalysis is very important and closely related to the two

points above it and the main reason why transition metals are so useful in synthetic

organic chemistry.1 The metals at the end of the transition series are more disposed to

exist in coordinatively unsaturated states, and thus, more prone to be active in catalytic

transformations. Late transition metals have a higher “catalytic power.”2

As early as in

1835, Jöns Jakob Berzelius defined his idea of “catalytic power” as the ability of

substances…“…to awaken affinities, which are asleep at a particular temperature, by

their mere presence and not by their own affinity…”3. Almost every functional group will

coordinate to some transition metals and thus altering the reactivity of the group to

provide functionalization that is impossible with conventional methods. The reactions are

site specific; leaving highly reactive functional groups untouched and, thus, avoids time-

consuming protection and subsequent de-protection steps. This specificity can also be

seen as a disadvantage, as a small modification of the reaction conditions might disturb

the system so much that the catalytic turnover will cease. We can also regard it from

another angle; it might be difficult to find optimal reaction conditions because the range

3

is so narrow. In other words, general conditions for transition metal-catalyzed reactions

are rare.1

Transition metal catalysis can roughly be divided into two groups, heterogeneous and

homogeneous catalysis. In heterogeneous catalysis, the catalyst is in a solid state or is

attached to a solid-phase, which facilitates catalyst recovery, but elevated temperatures

are often required, the specificity is low and it is more difficult to elucidate the

mechanism behind the transformation. The selectivity and the activity of homogeneous

catalysts under mild conditions is unbeaten by their heterogeneous counterparts. The

cobalt-catalyzed organic transformations described in this thesis, all take place in

solution using soluble cobalt-salts or complexes, and therefore belong to homogeneous

catalysis.4, 5

1.2. Transition metal catalysts

The application of the first-row transition metals, such as iron, cobalt and nickel, in

synthetic organic transformations has attracted increasing interest for reasons other than

simply their lower costs when compared to their higher homologues. A steadily growing

number of contributions have appeared in the literature where benchmark transformations

such as palladium-catalyzed coupling reactions were conducted with these first-row

transition metals. It became obvious that problems in palladium chemistry, such as the β-

hydride elimination, are of reduced importance in the chemistry of iron, cobalt and nickel

coupling reactions, probably because of lower rates for the β-hydride elimination

pathway. Therefore, reactions with the first-row transition metals can provide an

interesting alternative in established transformations and it is emphasized that cobalt, in

4

particular, can open up. In this chapter, some of the recent developments in the cobalt(II)

catalyzed organic transformations are described.

1.3. Cobalt-catalyzed cross coupling reactions

Over the past thirty years, the development of transition metal-catalyzed cross-

coupling reactions have revolutionized techniques for the formation of carbon-carbon

bonds, especially C (sp2) centers where typical SN

2 substitution can not operate.

6 The

development of efficient new carbon–carbon bond forming reactions by metal-catalyzed

cross-coupling is still progressing impressively and significant advances have been

achieved. Among the different catalysts, the most commonly employed and reliable metal

is palladium, especially when appropriate ligands are present. Although nickel complexes

have less general scope, they also have found applications in highly efficient cross-

couplings of organometallics with aryl halides. However, these catalyst systems have

disadvantages—the high cost of palladium and the high toxicity of nickel catalysts are

two of the more obvious ones—and their use in industrial applications is coming under

increasing scrutiny. Fortunately, inexpensive alternative catalysts are available in the

form of simple, effective iron and cobalt salts. These green reactions offer new means for

carrying out cross-coupling reactions both economically and ecologically. All these

catalysts have wide scope and excellent tolerance of various functional groups. There has

been much elegant work in iron-based catalysis, 7

however cobalt catalysts can sometimes

present a higher reactivity for various C–C bond forming reactions. Moreover, the low

cost of cobalt complexes and their interesting mode of action make them an attractive

alternative for use in cross-coupling reactions.

5

1.3.1. Cross-coupling reactions via organometallic compounds

The reactivity of Grignard reagents alone is quite extensive but their range of

applications can be extended significantly if they are used in conjunction with a catalyst.

Kharasch and Fields8 investigated the effect of transition metals such as cobalt in

reactions between organic halides and Grignard reagents as early as in 1941. Few

advances have been made in cobalt-catalyzed cross-coupling reactions until 1998 when

Cahiez and Avedissian9 reported the stereo and chemoselective reaction of vinyl halide

with an organomagnesium reagent catalyzed by Co(acac)2 (Scheme 1).

R3

R2

R1

X

+ RMgX

Co(acac)2 (3-8 Mol%)

THF-NMP (4 equiv)-5 °C to 0 °C, 5 min

R

R2

R1

R3

X= I, Br, Cl (55-90%)

1 2

Scheme 1: Cobalt-catalyzed alkenylation of organomagnesium reagents

More recently, Oshima and co-workers10-12

have demonstrated the cobalt catalyzed

cross coupling reaction (Scheme 2) between alkyl halides and allylic Grignard reagents.

Generally, palladium, nickel, and copper catalyzed coupling reactions are difficult for

two reasons: the reluctance of alkyl halides to undergo the oxidative addition step, and β-

hydride elimination from alkyl palladium and alkyl nickel. However, Oshima and co-

workers have overcome with the use of CoCl2(dppp) as catalyst.13

Oshima et al., also

reported the cross coupling of alkyl and benzyl halides or alkenyl triflates with benzyl,

aryl, heteroaryl, vinyl, and propargyl Grignard reagents (Scheme 2).14-19

Knochel and co-

workers20

reported the cross coupling of aryl Grignard reagents with a variety of

6

heterocyclic chlorides in the presence of 5 mol % CoCl2 or Co(acac)2. The best yields are

obtained using CoCl2 in diethyl ether. Homosilanes can also be prepared from

trimethylsilylmethylmagnesium chloride, 1,3-dienes and alkyl halides under cobalt

catalysis. The combination of CoCl2 and 1,6-bis(diphenylphosphino)hexane catalyzes this

in good to excellent yields, through a mechanism, which involves an alkyl halide derived

radicals (Scheme 3).

RX + Ph MgCl Ph R

R= alkyl (40-70%)

O

Br

BuO C5H11CoCl

2(dppe) cat

PhMgBr

THF, 0 °C, 30 min

OBuO C5H11

Ph

80% (dr= 55:45)

RX + ArMgX Ar-R

(56-99%)

(R,R)-L

NMe2

NMe2

(H3C)3Si

BrMg

Co(acac)3

(20-40%)

TMEDA, 25 °C15 min

(H3C)3Si

R

3 4

5

6

7

8 9

CoCl2(dppp) cat.

THF, 0 °C, 2 h

+RX

CoCl2 (5 mol%)

(R,R)-L (6 mol%)

THF, 25 °C, 15 min

(R, R) L= (R,R)-dppe

Scheme 2: Cobalt-catalyzed cross-coupling between Grignard reagents and alkyl halides

7

Scheme 3:Co(II)-catalyzed cross coupling between heterocyclic chlorides and aryl or

heteroarylmagnesium compounds

1.3.2. Cross-coupling with organozinc compounds

In general, like in the case of organomagnesium reagents, direct reaction of

organozinc reagent with electrophiles is low yielding and inefficient because of the

moderate intrinsic reactivity of zinc reagents. The reactivity of organozinc reagents can

be vastly enhanced by the use of transition metal catalysts. Gosmini and co-workers have

exploited the catalytic prowess of cobalt species by using them in a variety of cross

coupling reactions. The group has developed a cobalt catalyzed two component cross-

coupling reaction between alkylzinc compounds and acyl chlorides (Scheme 4) in

acetonitrile.21

Scheme 4: Synthesis of functionalized arylzinc reagents and their reaction with acyl

chloride

ArMgX

CoCl2

N

Cl

N

Ar

+

(5 mol %)

Et2O,-40 to 25

(35-91 %)

°C

1-96 h

CoBr2 + ZnBr2

ZnBr

FG

Br

FG

Cl

O

O

FG

(26-77%)10 11

PhBr (0.1 equiv) Zn (3 equiv)

CH3CN,CF3COOH, rt

2)

8

They also have shown that highly functionalized aryl bromides react with allylic

acetates in the presence of zinc dust in acetonitrile. In this reaction, catalyzed by CoBr2,

the allylic acetate present in the medium directly reacts with the arylzinc compound.22

In

1996, Knochel and co-workers had reported a CoBr2 catalyzed coupling of ally chlorides

or phosphates with alkylzinc halides or dialkylzincs.23

These reactions lead to the simple

SN2 cross-coupling product with the complete stereochemical retention across double

bonds. Dunet and Knochel have recently, extended this method to highly functionalized

diarylzinc reagents obtained by reacting aryl iodides with zinc.24

1.3.3. Synthesis of biaryl compounds

Unsymmetrical biaryl compounds are of considerable interest in organic chemistry.

Among the innumerable methods for the construction of aryl–aryl bonds, transition-

metal-mediated reactions constitute one of the main strategies used.25

Generally such

reactions involve the coupling of an organometallic reagent of boron, Sn, Si, Zn, Mg, Mn

with an aryl halide or pseudohalide. They all require the use of a stoichiometric

organometallic reagent, and typically the presence of a Ni or Pd complex as a catalyst.

Recently, it was shown that iron26

and cobalt27-30

catalysts could be employed as

alternatives to expensive precious metals, such as palladium, or toxic metals, such as

nickel in coupling reactions with organometallic reagents. Studies within the realms of

metal catalysis have provided several direct aryl–aryl bond-forming transformations for

organic synthesis. Catalytic direct arene C-H cross-coupling and the decarboxylative

coupling of aromatic carboxylates with aryl halides can be very efficient; however, these

methods often require the use of a base, high temperatures, and expensive catalysts. Other

9

reaction pathways include the palladium-catalyzed reductive coupling of two aryl halides

in combination with a reducing agent.

Very recently, Gosmini and co-workers have devised expedient route to the

functionalized biaryls including 2-(4-tolyl)benzonitrile, a key intermediate in the

synthesis of sartan derivatives and heteroaryl compounds. The reaction is catalyzed by

cobalt(II) bromide in combination with manganese dust (Scheme 7).31

In the proposed

mechanism (Scheme 8), cobalt shuttles between +1 and +3 oxidation states. The

mechanism is comparable with that of nickel-catalyzed formation of biaryls.

I

+CN

Br

20 mol% CoBr2

20 mol % PPh3

Mn (4 equiv)DMF/pyridine 6:1

NC2 equiv

70%1213 14

Scheme 7: Synthesis of unsymmetrical biaryls

10

Co(I)

X

1/2Mn

1/2MnX2

ArCoIII

X2

ArCoI

ArCoIII

X

ArX

Mn

MnX2

Ar1X

Ar-Ar1

Scheme 8: Proposed mechanism for the Co-catalyzed coupling reaction

1.3.4. Synthesis of diarylmethanes

Diarylmethanes have been shown to possess interesting biological and medicinal

properties and are ubiquitous structural constituents in pharmacologically important

molecules such as papaverine and beclobrate. These compounds also frequently appear as

subunits in supramolecular structures such as macrocycles, catenanes, and rotaxanes.32

The most general procedures for diarylmethane synthesis are the transition metal-

catalyzed cross-coupling between aryl halides and benzylic metals (usually prepared from

benzylic halides). The main difficulty with these methods remains the preliminary

preparation of the organometallic reagent, especially when the aromatic ring bears

11

reactive functional substituents. These preformed organometallic reagents often consist of

a magnesium, borane, manganese, stannane or zinc derivative and the cross-coupling

generally requires an expensive rhodium or palladium catalyst, or a toxic nickel catalyst

and typically sophisticated ligands. Some interesting copper-catalyzed reactions have also

been shown to form the methylene-linked biphenyl species.33, 34

Alternatively, Gosmini

and co-workers have developed a cobalt-catalyzed practical procedure35

for the synthesis

of diarylmethanes containing functional groups. In this reaction (Scheme 9), CoBr2

catalyzes the reductive cross-coupling between benzyl halide and a variety of electron

rich and electron deficient aryl halides to furnish diarylmethanes 16 in good yields. The

homocoupled products were formed in small amounts.

Scheme 9: CoBr2 catalyzed synthesis of diarylmethane

1.3.5. Mizoroki-Heck type reaction

Mizoroki-Heck reaction mostly employs aryl and vinyl halides as substrates.

However, with the use of a combination of cobalt(II) complex and trimethylmagnesium

reagent, the coupling of alkyl halides with vinyl halides (alkyl version of Mizoroki-Heck

reaction) can be accomplished. It is worth noting that alkyl chlorides, which are usually

less reactive in other transition metal catalyzed reactions, are alkyl sources in cobalt-

Cl

CoBr2 + Zn

0.1 equiv 1.5 equiv

FG

ZnCl

FG

Cl

FG

1. allyl chloride (0.3 equiv)

CH3CN, CF

3COOH

2. pyridine 4 mL

CoBr2 (23 mol%)

15 16

12

catalyzed reactions. The reaction allows various functionalities, including ester and amide

groups, to survive during the reaction (Scheme 10).36

17

18

R-X

Me3SiCH2MgCl (2.5 mmmol)[CoCl2(dpph) (2.5 mmol)

ether, reflux, 3 h

R-X= cC6H14Br, nC12H25Cl, tC4H9Br, 1-chloroadamentaneYilelds= 67-91%

Ar ArR+

17

18

R-X

Me3SiCH2MgCl (2.5 mmmol)[CoCl2(dpph) (2.5 mmol)

ether, reflux, 3 h

R-X= cC6H14Br, nC12H25Cl, tC4H9Br, 1-chloroadamentaneYilelds= 67-91%

Ar ArR+

Scheme 10: Cobalt-catalyzed Mizoroki-Heck reaction

1.3.6. Coupling reaction between alkenes and alkynes

Metal-catalyzed functionalization of carbon-carbon triple bond is another important

transformation in organic chemistry and cobalt catalysts in such transformations have

been explored. Oshima and co-workers revealed that cobalt(II) chloride catalyzes allyl

zincation of 1-aryl-1-alkyne with regio- and stereo-selectivity (Scheme 11).37

The

alkenylzinc intermediate 20 was trapped with several electrophiles to furnish

tetrasubstituted alkenes.

Scheme 11: Cobalt(II) chloride catalyzed allylzincation of alkynes

Ph

nC6H13

ZnBr

Cat. CoCl2

THF, rt, 48 h

nC6H13 Ph

ZnX

nC6H13 Ph

E

E+

E= H3O, I2, CH3COCl

19 20 21

13

Cheng and co-workers reported a broadly applicable method for reductive

intermolecular coupling of alkynes with activated alkenes (Scheme 12).38, 39

The reaction

afforded γ, δ-unsaturated carbonyls, acids, sulfones or nitriles such as 22. In the

intermolecular version of this reaction, a wide variety of nitrogen, oxygen, silicon or

sulfur-containing functional groups were tolerated. Cobalt-catalyzed method also has

advantages being highly chemo-, regio-, and stereoselective, and it can be used in the

intramolecular reaction to generate six or seven membered lactones. Cobalt-catalyzed

intramolecular and intermolecular coupling between alkenes and alkynes were also

reported by Macria and co-workers40-42

and Hilt and co-workers respectively.43

Scheme 12: Coupling of alkyne with an alkene

1.4. Synthesis of multiply silylated ethenes

Multiply silylated ethenes such as 1, 2-disilylethenes and 1, 1, 2-silylethenes are

intermediates for structurally interesting highly substituted alkenes. However, only a

limited number of stereo- and regio-selective procedures are available. An ate-type

trimethylsilylmethylcobalt reagent was found to react with dibromosilylmethane or

dibromosilylmethane to provide a concise synthesis of 1.2-disilylalkenes or 1,2,3-

trisilylethens in highly stereoselective and regioselective manner (Scheme 13).44

The

proposed mechanism (Scheme 14) includes halogen-cobalt exchange, 1,2-silylmethyl

R2

R1 + R3 R1

R2

R3

R1= aryl, alkyl, COOR; R

2= aryl, alkyl, SiMe3; R

3= COOR, CN, SO2Ph

Co(PPh2)I2, PPh3, Zn

CH3CN, H2O, 80 °C, 12 h

22

14

Scheme 13: Cobalt mediated concise synthesis of 1, 2-disilylethenes

L= larger alkyl groups S= smaller alkyl groups

Scheme 14: Proposed mechanism for the regio- and stereoselective silylation of alkenes

migration followed by β-hydride elimination. The β-hydride elimination favors a

sterically less demanding transition state, which leads to high regio- and stereoselctivity.

SiR3R3Si

BrBr

(R3SiCH2)4Co(MgCl)2

THF, -20 °C

CoSiR3

SiR3SiR3

R3Si

SiR3

Br

2-

-Br-

L SL

S

-

L

S

SiR3

L

SiR3

S

H

H

R3Si

Co

SiR3

L

SiR3

S

SiR3

H

H

Co

-H-Co

-H-Co

SiR3

SiR3

H

R3Si

S

L

SiR3

SiR3

H

R3Si

S

L

CoR3Si

SiR3SiR3

SiR3

R3Si

SiMe3Ph2MeSi

BrBr

SiMe3Ph2MeSi

H (iPrO)Me2Si

54-94 % streoselectivity

[(iPrO)Me2SiCH2]4Co(MgCl)2

THF, -20 °C

23 24

15

1.5. Carbonylative ring opening and ring expansion

A cobalt-catalyzed ring opening reaction of cyclic ethers was reported by Murai and

co-workers.45

Later, Watanabe demonstrated that cyclic ethers such as oxetanes and

oxiranes could undergo ring opening reaction (Scheme 15) with trimethylsilylamines

under insertion of carbon monoxide at atmospheric pressure.46

25 26 27

ONH

NH

O

PhTMS

TMSO

Ph

Co2(CO)2

CO (1 bar)

benzene, rt, 24 h

75 %

+

25 26 27

ONH

NH

O

PhTMS

TMSO

Ph

Co2(CO)2

CO (1 bar)

benzene, rt, 24 h

75 %

+

Scheme 15: Ring opening of oxetane

Alper first reported the formation of β-lactones from epoxides and β-lactames from

aziridines and co-workers.47

Alper used bis(triphenylphosphine)iminium cobalt

tetracarbonyl complex in combination with a Lewis acid, trifluoroborane etherate (BF3

OEt2 as catalyst. Coates and co-workers have later achieved the synthesis of β-lactones

from epoxides and β-lactams in good to excellent yields with use of biscyclopentadienyl

titanium cobalt tetracarbonyl or aluminium(salophen)cobalt tetracarbonyl complexes.48

Coates and co-workers have also succeeded in the double carbonylation of epoxides to

furnish succnic anhydrides with inversion of configuration by using bimetallic aluminium

porphyrine cobalt tetracarbonyl catalyst.49

A wide range of substituted epoxides were

used in this reaction and the catalyst loadings are very low which allows for easier

purification of the products.50

16

28 2980 °C, 24 h

O

O

On-Bu

n-BuPPNCo(CO)4 (2 mol%)

BF3.OEt2 (2 mol %)

28 2980 °C, 24 h

O

O

On-Bu

n-BuPPNCo(CO)4 (2 mol%)

BF3.OEt2 (2 mol %)

Scheme 16: Synthesis of β-Lactam from oxirane by CO insertion

30 3190 °C, 6 h, 99%, 99.5 ee

O

O

O

O[(CITPP)Al(THF) 2][Co(CO)4]

CO (bar)

30 3190 °C, 6 h, 99%, 99.5 ee

O

O

O

O[(CITPP)Al(THF) 2][Co(CO)4]

CO (bar)

Scheme 17: Double carbonylation of oxirane

1.6. Activation of sp3 C-H bonds

The functionalization of hydrocarbons, the main natural oil and gas constituents, has

been identified as a key research strategy for the development of economical and

sustainable global carbon management. Undoubtedly one of the most important

functionalization is selective oxidation; in particular the selective aerobic oxidation of

methane to methanol would be of great industrial interest.51-54

The first cobalt catalyzed

activation of sp3 C-H bond of alkanes was reported by Iqbal and co-workers. Depending

on ligand choice, these cobalt catalysts were effective in either the chlorination or

sulfochlorination of alkane substrates in good yields.55

The reaction is simply performed

by combining the alkane, sulfuryl chloride and the catalyst and heating to 85 ºC.

Sulfochlorination of polyethylene would lead to polymers with reactive sulfonyl

chlorides that could be used for reactive compatibilization and/or polymer grafting

reactions.

17

85 % 13%

R R

Cl

R

ClCoTMPP

CH3CNbenzene,

SO2Cl2

R=C4H7, C6H11, C8H15, etc.

+ +

85 % 13%

R R

Cl

R

ClCoTMPP

CH3CNbenzene,

SO2Cl2

R=C4H7, C6H11, C8H15, etc.

+ +

R= C3H7, C4H9, C8H15,etc.

Scheme 18:

Recently, Brookhart et.al. have developed catalytic dehydrogenation of alkyl amines

with a Co(I) catalyst. Amine substrates are protected with vinyl silanes, followed by

catalytic transfer hydrogenation, to yield a broad range of stable protected enamines and

1,2-diheteroatom-substituted alkenes, including several unprecedented heterocycles.

(Cp*)Co(VTMS)2 catalyzes transfer of hydrogenation under surprisingly mild conditions

with high chemo-, regio-, and diastereoselectivity (Scheme 19).56

3233

X= CH2, NMe, S, O

80 °C, 1-4 h

Si

N

X

Si

N

XCo(I)

2-4 Mol %

3233

X= CH2, NMe, S, O

80 °C, 1-4 h

Si

N

X

Si

N

XCo(I)

2-4 Mol %

Scheme 19: Cobalt(I) catalyzed dehydrogenation

1.7. Oxidation of alcohols to carbonyl compounds

The oxidation of an alcohol to the corresponding carbonyl product is a vital and

common transformation in synthetic organic chemistry. Consequently, there are a number

of diverse procedures are available in the literature. Chun Cai et.al., reported the

18

cobalt(II) perfluorooctane sulfonate (Co(OPf)2) catalyzed oxidation of various types of

alcohols to carbonyl compounds under atmospheric pressure of molecular oxygen in

fluorous biphasic systems.57

By simple separation of the fluorous phase, which contains

only pre-catalyst, the reaction can be repeated several times. An efficient method for the

oxidation of a variety of activated and non-activated secondary alcohols to the ketones

was developed by Bir Sain and co-workers.58

In this reaction, Co(acac)2 in combination

with NBS catalyzes the oxidation in acetonitrile (Scheme 20). Recently, method for the

oxidation of alcohols (aliphatic, aromatic and cyclic alcohols) to ketones was established

by Pedro et al. This reaction is carried out using a square-planar cobalt(III) tetraamine

complex as catalyst in the presence of dioxygen and pivaldehyde.59

34 35

OH

H

O

R1

R2

R1

R2

Co(acac) 2

NBS, acetonitrile

reflux

34 35

OH

H

O

R1

R2

R1

R2

Co(acac) 2

NBS, acetonitrile

reflux

Scheme 20: Co(acac) catalyzed oxidation of secondary alcohols to ketones

Very recently, Buxing Han and co-workers have demonstrated the aerobic oxidation

of secondary alcohols to ketones using alumina or Zinc oxide supported cobalt(II)

chloride or even unsupported cobalt(II) chloride as catalyst.60

The aerobic oxidation of

benzhydrol, 1-phenylethanol and cyclohexanol to corresponding ketones was carried out

in poly(ethylene glycol) (PEG-600)/supercritical CO2 (SCCO2) biphasic system. It was

shown that CoCl2·6H2O, Co(II)/Al2O3, and Co(II)/ZnO were all active and selective for

the reactions. The reactivity of the substrates followed the order benzhydrol > 1-

phenylethanol > cyclohexanol. Co(II)/ZnO was most stable and could be reused four

times without considerable reduction of activity.

19

1.8. Oxidation of Alkenes

The selective oxidation of alkenes to epoxides is one of the most important and

fundamental reaction in organic chemistry both at the laboratory and industrial scale.

Numerous catalysts have been developed using a variety of reagents to achieve this

purpose. However, most of these reagents are required in stoichiometric quantities.

Moreover these reagents are expensive and toxic. From an environmental as well as

economic point of view, catalytic oxidation processes, especially those, in which

molecular oxygen is used as primary oxidant, are particularly attractive. With these view

points, Pielichowski and co-workers61

made attempts and succeeded in developing an

efficient and selective catalytic system consisting of polyaniline supported cobalt(II)

chloride. Cobalt(II) chloride supported on polyaniline turned out to be particularly

effective in oxidation of alkenes with terminal carbon-carbon double-bond and

cycloalkenes.

CH3CN, 60 °C

RO

R

R1

CHO

R1

CoCl2 (0.3 mol%), O

2

R=alkyl, aryl R1= alkyl, aryl, H

CH3CN, 60 °C

RO

R

R1

CHO

R1

CoCl2 (0.3 mol%), O

2

R=alkyl, aryl R1= alkyl, aryl, H

Scheme 21: Cobalt(II)-catalyzed oxidation of alkenes to oxiranes

20

Chavasiri and co-workers62

have recently disclosed that the epoxidation of alkenes

can be achieved using cobalt(II) calix[4]pyrrole as catalyst and aldehyde/oxygen as an

oxidant. Co(II) meso-tetrakis (4-methoxyphenyl)-tetramethyl calix[4]pyrrole was found

to show the best catalytic performance to provide the corresponding epoxide in high

yields with excellent selectivity stereo- and regioselectivity under mild conditions.

1.9. Cyclopropanation

Metal-catalyzed cyclopropanation of double bonds with carbenoids obtained from

diazo compounds is a well known reaction in organic synthesis. The control of both the

diastereoselectivity and the enantioselectivity has drawn much attention over the past

years. There are various catalysts, such as copper, cobalt, ruthenium and rhodium

complexes, that are employed for this purpose and that exhibit excellent stereoselectivity

and, in general, result in the formation of the trans products. Recently Katsuki studied

metallosalen complexes, which are known to be efficient catalysts for oxene and nitrene

transfer reactions. He reported the use of chiral cobalt(salen)63

complexes for the

analogous carbenoid transfer reaction (Scheme 22). Various styrene derivatives reacted

with simple a-diazo esters with diverse salen derived cobalt complexes to produce the

cyclopropanation product 41 in excellent yield, diastereoselectivity and enantioselectivity.

The cis/trans relationship is influenced by the nature of the ligand and the cobalt centre.

Cobalt(III) complexes seem to favor the generation of the trans isomer, and cobalt( II)

complexes, the cis isomer (Scheme 22).

21

OMe

+N2

O

OtBu

MeO

OtBu

O

36 37 38

Co(salen) 5 mol%

toluene, rt84 %, 96 % ee

N2

O

OEt+Ph

Co(Porphyrin)

83 5, 75%, eetrans/cis 94:6

OEt

O

PhH

39 40 41

Scheme 22: Cobalt(salen) catalyzed Cyclopropanation

Gao et.al., reported64

the use of dinuclear Robsen-type coupled chiral salen

complexes for the same reaction. Zhang and co-workers reported the use of cobalt

porphyrin65

complexes for the asymmetric cyclopropanation of styrene derivatives with

ethyl diazoacetate under mild conditions (Scheme 23). A great number of structurally

diverse porphyrin ligands tested and a general preference for the trans isomer was shown.

N2

O

OEt+Ph

OEt

O

PhH

42 43 44

Co(Porphyrin)

75%, eetrans/cis 94:6

Scheme 23: Co (porphyrin) catalyzed cyclopropanation

Rose and co-workers very recently reported a chiral cobalt(II)-binaphthyl pophyrins

catalyzed asymmetric cyclopropanation of olefins. Cyclopropanation of a variety of

substituted styrenes with diazoacetate was achieved in good yields and enantioselectivity

unto 90 % were obtained.66

The positive catalytic effect of nitrogen promoter, N-

methylimidazole, on reaction rate and enantioselectivity was demonstrated.

22

1.10. 2+2 Cycloaddition reactions

The supra-supra facial [2+2] Cycloaddition of alkenes or alkynes is thermally

forbidden by Hoffmann-Woodward rules. Nevertheless, these reactions are allowed

photochemically, by free radical mechanism, by Lewis acid catalysis. Krische reported

the first example of an intramolecular, diastereoselective [2+2] cycloaddition of bis-

enones to cyclobutanes. The reaction was catalyzed by cobalt species (Scheme 24).67

The

Scheme 24:

reaction was restricted to aryl substituted ketones and the formation of bicyclo[3.2.0]

backbones. Cheng and co-workers reported the reaction (Scheme 25) of terminal as well

as internal alkynes with bicyclic alkenes 47 such as benzooxanorbornadiene to highly

functionalized cyclobutenes with the inexpensive and versatile CoI2(PPh3)2,

triphenylphosphine and zinc catalyst system.68

Hilt very recently reported an extension of

this methodology using a cobalt catalyst system, [CoBr2(dppp), Zn, ZnI2]. This method is

applicable not only for norbornyl derivatives as starting materials but also for

acenaphthylene and even cyclobutene derivatives such as 50 (Scheme 25).69

Ph O

PhO

Ph

OO

Ph

HH

Co(dpm)2, PhMeSiH2

DCE, 50 °C

72 %45

46

23

Scheme 25: Cobalt-catalyzed [2+2] cycloaddition of alkene with an alkyne

1.11. Five member ring formation

Pauson-Khand reaction undoubtedly is one of the most valuable in the construction of

five membered rings. It is a [2+2+1]-cycloaddition of an alkyne, an alkene and carbon

monoxide. Chung and co-workers combined a cobalt-catalyzed Pauson-khand type

reaction in tandem with other cobalt-catalyzed cycloaddition reactions (Scheme 27).70

After a [2+2+1] cycloaddition, a cyclopentadienone intermediate formed and reacted with

either 1,3-dienes in a Diels-alder reaction or with two other alkynes in a [2+2+2]-

cycloaddition reaction. Alternatively, a dimerization by Diels-Alder reaction of [2+2+1]-

cycloaddition product led to the formation 51, which undergoes rearrangement with the

extrusion of CO yielded 52.71

+Ph

Ph

CoBr2(dpm)2

PhMeSiH2

DCE, 50 °C, 91 %

Ph

Ph

H

H49

50

O +

COOEt

SiMe3

O

SiMe3

COOEt

47

48

CoI2(PPh3)2

Ph3P, Zn

toluene90 °C, 24 h

24

CO2EtEtO2C

O

CO2Et

CO2Et

EtO2C CO2Et

O

CO2EtEtO2C

Co/C, CO (30 atm)

THF, 150 °C57 %

EtO2C CO2Et

O

O

CO2Et

CO2Et

4950

52

51

Scheme 27

1.12. Dipolar Cycloaddition reactions with nitrenes

The 1,3-dipolar cycloaddition of nitrones to alkenes is a very useful reaction in the

construction of isoxazolines and can be catalyzed by various Lewis acids. Recently,

Desimoni, Kanemsa and Suga carried out studies on these reactions using a diverse Lewis

acids including cobalt salts.72

Yamada and co-workers have reported the use of 3-

oxobutyldenimniatocobalt(III) complexes for the enantioselective 1,3-dipolar

cycloaddition of nitrones with α,β-unsaturated aldehydes to furnish 55 (Scheme 28).

N+ O

-Ph

H

BrOHC

+

1. chiral Co complex5 mol %

2. NaBH4, EtOH

85 %, 85 % ee

BrN O

Ph

H

H

56 57 58

Scheme 28:

25

1.13. Formation of rings containing six to ten members

Cobalt catalysts are also used in the formation of rings containing six to ten members.

Most Diels-Alder reactions between neutral substrates require drastic conditions. Hilt and

co-workers developed a catalyst system consisting of Co(dppe), zinc iodide and zinc or

tertiary butylammonium borohydride to overcome this problem (Scheme 25).73,74

R1 R2

R3

+ R1

R3

R2

59

CoBr2(dppe)

ZnI2

Zn or Bu4NBH4

CH2Cl2, rt

Scheme 29: Cobalt-catalyzed Diels-Alder reaction

Cobalt complexes also catalyze the construction of six membered rings by homo Diels-

Alder reaction, [2+2+2] cyclotrimerisation of alkynes, [2+2+2] cyclotrimerization

between two alkynes and one alkene, cyclotrimerization of alkynes with nitriles.

Due to their abundance in natural products, the synthesis of seven membered rings is one

of major goals of organic chemists. Seven membered rings are constructed by [3+2+2]

cycloaddition, [5+2] cycloaddition, [4+3] cycloaddition reactions. Nicholas type reaction,

[5+2] cycloaddition reaction of silylenol ethers was catalyzed by cobalt complex and was

highly stereoselective. The construction of eight membered rings are achieved by [6+2]

cycloaddition, [4+2+2] cycloaddition reactions. Buono and co-workers recently reported

a new cobalt catalyzed [6+2] cycloaddition of cyclohepta-1,3,5-triene with terminal

alkynes for the construction of bicyclic systems. The [4+2+2] cycloaddition is a powerful

method for the construction of eight membered rings. Snyder reported an efficient cobalt

system consisting of a mixture of cobalt(II) iodide with 1,2-bis(diphenylphophino)ethane,

zinc and ZnI2. Snyder also demonstrated the application of this methodology in natural

26

product synthesis.75

Cobaloxime dienenyl complexes were found to catalyze Diels-Alder

reactions with tropone derivatives (Scheme 30).76

Welker observed the [6+4]

cycloaddition product. Tropone was conveniently synthesized in excellent yield by

cobalt-catalyzed [6+4] cycloaddition.

(L)Co

+ O

67 %

(L)Co

O

60 61 62

Scheme 30: 6+4 Cycloaddition reaction

1.14. Cobalt(II)-catalyzed Friedel-Crafts cyclization

Stereoselective construction of medium-sized poly-functional rings is an important

subject because these structures are found in a number of natural products. Nagumo and

co-workers developed a novel cyclization of eight- and nine-membered iminium ions

using a Co2(CO)6 complexed acetylene unit.77

The cyclization was achieved due to the

bent conformation of the complex, which facilitates access of the aromatic ring to the

iminium ion generated from 63.78

(OC)3Co Co(CO)3

MeO

MeO

N

MeO

Ts

TMSOTf

CH2Cl

2

MeO

MeO

N

Ts

Co(CO)3(OC)3Co

63 64

Scheme 31

27

Nagumo very recently developed a method for constructing poly-functional eight-

membered carbocycles based on the endoselective Friedel–Crafts reaction of

vinyloxiranes with Co2(CO)6- complexed benzeneacetylene. The cyclization showed high

stereoselectivity and regioselectivity for the opening of the epoxide. Furthermore,

decomplexation of the cyclization product proceeded smoothly. This reaction is expected

to provide a useful method for the synthesis of natural products with eight-membered

carbocycles.

(OC)3Co Co(CO)3

R2

R3

MeOOC

OR1

R2

R3

Co(CO)3(OC)3Co

MeOOC

OHR

1

65

66

BF3.Et

2O

CH2Cl

2, -30 °C

R1, R

2, R

3= H, OMe

Scheme 32

Decomplexation was performed under either oxidizing or reducing conditions.Treatment

of cyclic molecule 67 with ceric ammonium nitrate afforded 68 in 72% yield. On the

other hand, 67 was transformed into poly-functional cyclooctene 69 in high yields upon

treatment with tributyl tin hydride in toluene at 70 ºC (Scheme 33).

28

R2

R3

Co(CO)3(OC)3Co

MeOOC

OHR1

MeO

MeOOC

OH

OMe

O O

O

MeO

MeOOC

OH

MeO

67

68

69

CAN, CH2Cl

2

Bu3SnH, toluene

70 °C

Scheme 33

1.15. Miscellaneous reactions

Kanemasa and co-workers introduced an enantioselective Michael addition reaction

catalyzed by cobalt(II) perchlorate hexahydrate and (R,R)-4,6-dibenzofurandiyil-2,2’-

bis(4-phenyloxazoline) in a 1:1 mixture of ter-butyl alcohol and tetrahydrofuran to

generate chiral polyfunctionalized ketones (Scheme 34).79

Brookhardt et al recently

described an interesting hydrogen shift reaction catalyzed by a CpCo(vinylsilane)2

complex wherein, an enamine was generated by the abstraction of hydrogen and

transferring it to vinylsilane group (Scheme 35).56

N

N

CH3

CH3

OCH3

+NC

NC

CH3 NN

CH3

O

CH3

CH3

CN

CN

CH3

(R,R)-DBFOX-Ph (10 mol %)

Co(ClO4)2(H2O) (10 mol %)

tBuOH

-THF, (1:1), rt.,

8 h,

Scheme 34: Cobalt(II)-catalyzed enantioselective Michael addition

29

N CH3

Si

CH3

CH3

CH2N CH3

SiCH3 CH3

CH3

CpCo(H2C=CHSiMe3)2

(4 mol%)

C6D12. 80 °C, 1 h

Scheme 35: Cobalt-catalyzed hydrogen shift

A recent study by Forbes and co-workers showed that Jacobsen’s Co(II)salen complex

could be used in hydrolytic kinetic resolution of chiral oxiranes.80

OAr

(R,R)Co(II)salen complex

H2O, CH

3CN, CH

2Cl

2

OAr

Scheme 36

1.16. Conclusion

It is well known fact that cobalt has high potential for catalyzing various reactions. A

small change in the catalyst system or parameters such as solvent, ligand or

concentrations of the reaction lead to new unexpected results. Even simple salts like

cobalt(II) chloride can be tuned to yield wonderful results by choosing proper solvent,

ligand and other parameters. The growing interest in cobalt-catalysis among chemists,

and the increasing number of interesting and astonishing reactivities and new reaction

pathways inspired us to venture into the investigation of cobalt in some of the organic

transformations. Indeed, we could succeed in developing new highly efficient synthetic

methodology for Friedel-Crafts acylation of some of the electron rich aromatics such as

30

anisole, thioanisole, and toluene and also a highly efficient procedure for the synthesis of

nitriles from dehydration aldoximes.

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