a new multicomponent reaction catalyzed by [lewis acid] [co(co)4

A New Multicomponent Reaction Catalyzed by[Lewis acid]+[Co(CO)4]- Catalyst

T. L. Church, C. M. Byrne, E. B. Lobkovsky, andG. W. CoatesJACS ASAP

DOI: 10.1021/ja069065d

Current Literature - June 16, 2007

Maciej Walczak @ Wipf Group 1 6/20/2007

Multimetallic Catalysis

- Majority of the catalytic systems arebased on catalytic-stoichiometricsystems (NHK coupling).

- Although sequential addition of metalcatalyst has been successfully applied,there are only few well-defined,multimetallic (multifuntional) catalyticsystems (Sonogashira coupling,Wacker oxidation).

- Ideally, multimetallic catalyst(heteronuclear) would be superior to amixture of salts.


Epoxide Carbonylation

- Detailed mechanistic studies showed thatreaction rate is independent on epoxide andCO, but 1st order in catalyst.

- The rate is strongly dependent on thepolarity of the solvent.

- Rate determining step is lactone formation.

- Solvents with a strong donating capabilitieshelp to stabilize aluminum cation formedafter lactone formation.

Coates

J. Am. Chem. Soc. 2006,, 128, 10125

NN

O OAl

O

Ot-But-Bu

t-But-Bu [Co(CO)4]-1 =


Epoxide Carbonylation

Coates J. Am. Chem. Soc. 2002, 124, 1174Coates Angew. Chem. Int. Ed. 2002, 41, 2781Coates J. Am. Chem. Soc. 2005, 127, 11426

- A practical procedure for carbonylation of epoxides has been also developed (1 atm CO, yields>98%).

Coates Org. Lett. 2006, 8, 3709

O

R+ CO

NN

N NCr

Et

Et

EtEt

Et

Et

EtEtR

THF

THF

Co(CO)4-

+

O

R

O

>88%

R = various alkyl groups

NN

O OAl

O

Ot-But-Bu

t-But-Bu [Co(CO)4]-

O

R+ CO

O

R

O

60-90%or Cp2Ti(THF)2

+ [Co(CO)4]-


Carbonylation of 4-membered Heterocycles

NN

O OAl

O

Ot-But-Bu

t-But-Bu [Co(CO)4]-1 =

X

R1 R2

+ COCatalyst X

R1 R2

O


Synthesis of Anhydrides

Inversion of configuration is consistentwith mechanism involvingnucleophilic displacement by CO.

Coates J. Am. Chem. Soc. 2004, 126, 6842

OO

R R1

OO

RR1

O

Catalyst (0.33 - 5 mol%)200 psi, PhMe, 24 h

yields: 90-99%R = H, MeR1 = only alkyl

+ CO

OO

Me

OO

Me

O

Cat., 55 o

200 psi, PhMe, 24 h+ CO

99% ee 99% ee

OO

Me

O

88% ee

Cat., 80 o

200 psi, PhMe, 24 h

However, partial racemization was observed when the reaction was carried out at elevatedtemperatures (80 o).

O

Me+ CO

NN

N NAl

R1

R1

R

R1

R1 R R1

R1

R

R1R1

R

THF

THF

Co(CO)4-

+

R = 4-ClC6H4

R1 = H

OO

O

97%

Direct insertion into epoxides:Coates Chem. Comm. 2006, 657


Insertion into Nitrogen Heterocycles

N

R3 R2

R1

N NO O

R3R3R2

R2

R1R1

CO

60 atm

+ +

N I

Cat.

Entry R1 R2 R3 Cat. Mol% N I

1 B n H M e A 5 9 0 ND

2 B n H M e B 5 5 0 ND

3 B n -(CH2)4- A 5 8 0 ND

4 B n -(CH2)4- B 5 < 5 ND

5 B n -(CH2)4- Co2(CO)8 8 2 8 ND

6 To s H M e A 5 3 5 ND

7 To s H M e B 5 9 9 ND

8 B n M e CH2OTB S A 5 9 0 5

9 B n M e CH2OTB S Co2(CO)8 8 9 2 8

Coates Angew. Chem. Int. Ed. 2002, 41, 2781

Other heterocycles, such as azirines, α-lactams, diaziridines, azetidines and oxazilines havebeen described.

N

OAr

N

O

Ar

O

+ CO 13 atm

5 mol% Co

60 oC, 24 h, THF

variable yield9-92%


Title Paper - Experiment Design


Title Paper - Optimization Studies


Title Paper - Reaction Scope


Lewis Acids Promote Acyl Migration


Summary and Outlook

• Lewis acids combined with nucleophilic metal carbonyls are powerful catalyst forcarbonylations of epoxides and aziridines.

• Detailed mechanistic studies allowed for development of efficient multicomponentreactions using epoxides, CO, and isocyanates.

Future Directions:Reaction scope needs to be improved - since CO is an invariable component,other electrophilic acceptors may be used.

Although some efforts were directed towards development of enantioselectiveversion of the epoxide carbonylation, more research is needed to develop optimalconditions for kinetic resolution.

A concept of Lewis acid activation followed by trapping by nucleophilic metalcenters could be potentially extended towards other substrates.


a new multicomponent reaction catalyzed by [lewis acid] [co(co)4

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