fischer carbenes

Fischer Carbene Complexes in Organic Synthesis

1

A.B. Charette J. Am. Chem. Soc. 2001, 123, 11829.

Baran Group Meeting1/31/2007

Ke Chen

German inorganic chemist. Born in Munichon November 10, 1918. Studied at MunichTechnical University and spent his careerthere. Became director of the inorganicchemistry institute in 1964. In the 1960s,discovered a metal alkylidene and alkylidynecomplexes, referred to as Fischer carbenesand Fischer carbynes. Shared the Nobel Prizein Chemistry with Geoffery Wilkinson in 1973,for the pioneering work on the chemistry oforganometallic compounds.

Ernst Otto Fischer (1918 - )

Isolation of first transition-metal carbene complex:

(CO)5W CO

LiMe

(CO)5W

Me

O

CH2N2(CO)5W

Me

OMe

E. O. Fischer, A. Maasbol, Angew. Chem. Int. Ed., 1964, 3, 580.

Representative Fischer Carbenes:

Me OMe

W(CO)5

Ph Ph

Cr(CO)5

Ph NEt2

Fe(CO)4

Ph OTiCp2Cl

Mn(CO)2(MeCp)

Me OMe

Co(CO)3SnPh3

Comparision of Fisher Carbene and Schrock carbene:

Schrock carbenes are found with:

high oxidation states early transition metals Ti(IV), Ta(V) non pi-acceptor ligands non pi-donor substituents

Schrock carbene, named after Richard R. Schrock, is nucleophilic at the carbene carbon atom in an unpaired triplet state.

Representatives:

Cp2Ta

CH2

CH3

Fischer carbenes are found with :

low oxidation state metals; middle and late transition metals Fe(0), Mo(0), Cr(0), W(0); pi-electron acceptor metal ligands; pi-donor substituents on methylene group such as alkoxy and amino groups.

Persistent carbenes, isolated as a crystalline solid by Anthony J. Arduengo in 1991, can exist in the singlet state or the triplet state.

Foiled carbenes were defined as "systems where stabilization isobtained by the inception of the facile reaction which is foiled by the impossibility of attaining the final product geometry". They only exist in the singlet state.

Other Types of Stabilized Carbenes:

Rolf Gleiter, Ronald Hoffman J. Am. Chem. Soc. 1968, 90, 5457 - 5460.

Jean-Luc Mieusset and Udo H. Brinker J. Am. Chem. Soc. 2006, 128, 15843 - 15850.


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Ke Chen

Advantages over regular carbenes - From fleeting intermediates to powerful reagents

1. Improved stability

Typical carbenes such as diphenyl carbene have lifetimes in the nanosecond regime.

Most Fischer carbene complexes are stable to air and water and todilute acids and bases. Despite the high dipole moment of thesecomplexes (~ 4 - 5 Debye), most complexes can be purified bychromatography on silica gel with hexane as eluent and are usuallythe first compounds to elute. Identification of the fractions from thecolumn containing the carbene complex can simply be done by eyeon the basis of their color. The colors of complexes bearing alkoxygroups as the heteroatom-stabilizing group tend to correlate with the hybridzation of the carbon substituent of the carbene carbon. Thosewith sp3 carbons usually are yellow, those with sp2 carbons arenormally red and those with sp hybridized carbon substituents areinvariably an intense purple/black color.

2. Excellent functional group compatibility - serving as blocking groups in organic synthesis.

J. Barluenga. J. Am. Chem. Soc. 2002, 124, 9056 -9057.

3. Improved reactivity and selectivity

MeO

Cr(CO)5

RT, 3 h

70 %

MeO

Cr(CO)5

MeO

Cr(CO)5

MeO

O

thermal conditions: RT, 7 months, 54 %

MeO

O

MeO

O

92 : 8

70 : 30

W. Wulff. J. Am. Chem. Soc. 1990, 112, 3642.http://www.chemistry.msu.edu/faculty/wulff/myweb26/research/carbenes.htm

AlCl3, 0.5 h , 50 % 95 : 5

[Cr]

OMe

Ph

OTMS

Et

Ph O

[Cr]

OMe

Et

O[Cr]

Ph EtH

H

BuLi, THF, -78 oC

75 %

3 equiv of CH2CHCH2Li, THF

-78 oC to RT, then SiO2

71 %


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Ke Chen

Synthesis of Fischer carbene complexes:

1. Standard Fischer route

M(CO)6

R1Li(OC)5M

OLi

R1

RX(OC)5M

OR2

R1

HNR3

R4

HS R3

(OC)5M

SR3

R1

(OC)5M

NR3R4

R1

M = Cr, Mo, W

R1 = alkyl, aryl, vinyl

RX = R23O+BF4

-, R2OSO3F

R3, R4 = H, alkyl

(OC)5M

OLi

R1

Me4N+Br-

(OC)5M

O-NMe4+

R1

X R2

O

(OC)5M

O

R1

R2

O

R3OH

(OC)5M

OR3

R1

M = Cr, W

R1 = alkyl, aryl, vinyl

R2 = Me, tBu

X = Br, Cl

R3 = terpene, sugar skeletons

2. Hegedus-Semmelhack approach

M(CO)6

C8KK2[M(CO)5]

R1 Cl

O

(OC)5M

OK

R1

R2X(OC)5M

OR2

R1

(OC)5M

O-

R1

R1 NR3R4

O

NR3R4

TMSCl(OC)5M

NR3R4

R1

M = Cr, WR1 = alkyl, aryl, vinyl

This is the most direct and general approach to Fischer carbenecomplexes;Limitations are the availability of organolithium compoundand the alkylation reagent.

This is the standard approach to optically active Fischer carbenecomplexes bearing alkoxy substituents.

R2X = R23O+BF4

-, R2OSO3F

R3, R4 = H, alkyl

This strategy combining an organoelectrophile and a metal nucleophilecan be extended to the synthesis of aminocarbene complexes.

Recent reviews:

W. D. Wulff, in Comprehensive Organometallic Chemistry II, ed.A. W. Abel, F. G. A. Stone and G. Wilkinson, pergamon Press, Oxford, 1995, vol. 12, p. 469L. S. Hegedus, ibid., vol. 12, p. 549.


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Ke Chen

Reaction pattern of carbene complexes:

OC

Cr

CO

OC

OC CO CR2

O R

H

E

Nu

B

C

A

B

(OC)5M

OR

R

(OC)5M

OR

R

Part I: Ligand-centered

Pattern A: Addition of nucleophiles

(OC)5Cr

OMe

Ph

NH2R(OC)5Cr

OMe

PhNHR

H(OC)5Cr

NHR

Ph

- MeOH

(OC)5Cr

OMe

Ph

NMeO

Ph

Cr(CO)5

N

?

(OC)5Cr

OMe

OPh

OLi

Li

O

O

Ph

Cr(CO)5

THF, -80 oC to RT

50 %

J. Barluengal, J. Chem. Soc., Chem. Commun. 1993, 1068

H. Fischer, Chem. Ber. 1980, 113, 193

Pattern B: Bond formation via metal carbene anions

(OC)5Cr

OMe 1. nBuLi

2. O

(OC)5Cr

OMe

OLi

(OC)5Cr

O

(OC)5Cr

OMe

O

OMe

pKa = 12 pKa = 25

(OC)4Cr

N

CH3

N

O

H3C

Ph

CH31. nBuLi2. PhCHO3. HOAc / Ce(IV)

60 %, > 96 % de

N

O

N

O

Ph

OH

Ph CH3

CH3

Pattern C: Transformation of metal carbenes to metal carbynes

W. Wulff, J. Org. Chem., 1994, 6882.

B. A. Anderson, J. Am. Chem. Soc., 1993, 115, 4602.

For reviews on reaction pattern of carbene complexes, see "Carbene Chemistry : From Fleeting Intermediates to Powerful Reagents", chapter 8.

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Ke Chen


Part I: Ligand-centered

Cycloaddition reactions:

[2 + 2]

(OC)5W

OMe

CH3

OMe

RT, 12 h

87 %

CH3

OMe

(OC)5W

H3CO

[3 + 2]

K. L. Faron, J. Am. Chem. Soc. 1988, 110, 8727 -8729.

(OC)5W

OMe

CH3

TMSCHN2

hexanes, RT

4.5 h, 87 %

(OC)5W

OMe

N

NH

H3C

W. D. Wulff, J. Am. Chem. Soc. 1986, 108, 5229 -5236.[4 + 2]

(OC)4Cr

N

N

O

H3C

Ph

CH3

DCM, RT, 12 h80 %,single isomer

CH3

OCH3

TBSO

(OC)4Cr

N

N

O

H3C

Ph

CH3

OTBS

CH3

CH3O

W. D. Wulff, J. Am. Chem. Soc. 1997, 119, 6438 -6439.

Diels-Alder reaction of boroxycarbene complexes:

Br

N

1. t-BuLi, Et2O

2. Cr(CO)6, Et2O

3. BF3. Et2O, RT

N

BO

F

F(OC)5Cr

N

Me

Ph

1.THF, -78 oC to RT

85%

2. 3N HCl, THF, RT

95 %

N

BO

F

F(OC)5Cr

O

HBr, DCM, RT

85 %

CHO

N

O

J. Barluenga. J. Am. Chem. Soc. 1998, 120, 2514 -2522.

Intramolecular Pauson -Khand reaction:

(OC)5W

NH

Ph

[Co2(CO)8]

75 %

(OC)5W Ph

O

J. M. Moreto. Angew. Chem. Int. Engl. 1991, 11,1470.


Miscellaneous cases

(OC)5W

OLi (-) -Ipc2BCl, Et2O

-78 oC to RT

BOH

Ipc

H2O2, NaOH83 %, > 99 % de

Ph

Ph

OHOH

Ph

J. Barluenga, J. Am. Chem. Soc,, 1996, 118, 6090 -6091.

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Ke Chen


Part II: Metal-centered

(OC)5Cr

OR1

R2

(OC)4Cr

OR1

R2

(OC)4Cr R2

OR1

Olefin MetathesisCyclopropanation

1. Reaction with olefins

"The functionalized Ru Fischer-typecomplexes are active in a variety ofolefin metathesis reactions, althoughwith significantly lower rates than the corresponding carbon analogues."

General carbene complexes used in cyclopropanation reactions:

Fe

Cp

OC

R*Ph2PH

Me

Fe

Cp

CH2OC

OCCr(CO)5

Me OMe

W(CO)5

Ph OMe

W(CO)5

Ph H

Mo(CO)5

Bu OMe

Cr(CO)5

Ph OMe

Cr(CO)5

OMe

(leads to olefinmetathesis product)

(less stable )

Suitable olefins:

EWG EWGAlkyl

EWG

Alkyl

R2

R1R2

R1

R1, R2 = akyl, aryl

R2

R1

R3

R1, R2 and R3 = alkylrequires stronger

electrophilic metal carbenes

R, H. Grubbs, Organometallics. 2002, 21, 2153 -2164.

Cr(CO)5

Me OMeEt

THF, 100oC

55 %

Me

MeO

H

Et

CrEt

MeO

H

R

(CO)4

H

REt

MeOCr(CO)4

CrMeO

Et

H

R

(CO)4

H

RMeO

EtCr(CO)4

Me

MeO

H

Et

J. Am. Chem. Soc. , 113, 23, 1991, 8916-8921

(OC)5Cr

OMe

Fe

DMF, 152 oC

88 %, 97 % de Fe

H

OMe

Cr(CO)5

OMe

O

Cl 85oC,12 hO

O

O

Chemtracts - Organic Chemistry. 17, 67 -71, 2004


85 %

intermediate A

favored

disfavored

O

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Ke Chen

D. L. Boger, J. Am. Chem. Soc,, 1995, 11839.


2. Benzannulation (Dotz reaction)

OMe

Cr(CO)5

OMe

Cr(CO)4

RS RL

OMe

Cr(CO)4

RS

RLOMe

RSRL

CrOC CO

OC CO minimizationof interaction

OMe

RS

O

RL

O

RL

RS

OMe

Cr(CO)3

Cr(CO)3HO

RL

RS

OMe

Cr(CO)3



Suitable metal:

Cr (metal of choice)Mo ( furan formation occasionally)W (favor 3 + 2 cycloaddtion)Mg (low yields)

Compatible substitution pattern:

Aryl carbenes with various substituentsNaphthyl and heteroaryl carbenesVinyl carbenes bearing alkyl substituents

Electron - neutral alkynes with varioussubstituents

OMe

Cr(CO)5

O Oether, reflux

OMe O

O

nPr

O OH

51 %

(OC)5Cr

OMe OCPh3 TBSCl, hunig base

OTBS OCPh3

Cr(CO)3> 92 % d. e.

MeO

OO

Cr(CO)5

OMe

OO

NEtO

TBSO

OTBS

OO

MeO

OO

OMe

OH

OTBS

N

OTBSBnO

EtO

fredericamycin A

OMe

BnO

35 %

M. F. Semmelhack, Tetrahedron, 1985, 5803.

W. D. Wulff, J. Am. Chem. Soc,, 1994, 116, 6449.

- CO

+ CO

8


Ke ChenFischer Carbene Complexes in Organic Synthesis

3. General Annulation of Fischer carbenes with alkynes and alkenes:



(OC)5Cr

CH3

OMe

O

PhC3H7

THF, 105 oC, 15h

O

CH3

OMeCH3

Ph

O

O

CH3

OMeCH3

Ph

O

48 % 18 %

J. Am. Chem. Soc. 1991, 113, 5459 - 5461

(OC)5Cr

CH3

OMe

O

Me

MeOO

OMeMe

13 % 10 %Organometallics, 1990, 9, 3014 - 3015

CO2Et

(OC)5Cr

CH3

OMe H

Bu

OMe

CO2Et

66 %

J. Am. Chem. Soc. 1994, 116, 6719 - 6732

(OC)5Cr

Ph

OMe

O

O THF, 70 oC, 24 h

CO, 73 %, d. r. = 3 :1

O

O OMe

Ph

H

J. Am. Chem. Soc. 1992, 114, 10665 - 10666

(OC)5Mo

OMe

Me

Ph

O

CH3

THF, 70 oC, 14 h, 40 %

O

CH3

Ph

O

CH3OMe

J. Am. Chem. Soc. 1990, 112, 1645 - 1647

(OC)5Cr

OEt

SiMe3

NMe2Ph

THF

3EtO

Ph

Ph

Ph

NMe2

EtO

Ph

Ph

Ph

NMe2

64 : 36Angew. Chem. 1999, 111, 1369

(OC)5Cr

OMe

Ph

MeMe

TMSO OTMS

THF, 90 oC

71 %

O O

Ph

Ph

MeO Me

Me

J. Barluenga, Org. Lett., 2006, 8, 2703 -2706.

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Ke ChenFischer Carbene Complexes in Organic Synthesis

State of art:

Group 6 metal carbenes in catalytic carbene transfer reactions

(OC)5M

R

OMe

M = Cr, W

stable, storable, less reactive

LnM

R

OMe

M = Pd, Cu, Rh

reactive, unstable

multi-faced chemistry

(OC)5Cr

O

O

1. [Cu(MeCN)4][PF6], DCM2. DCM, Et2O

Cu

O

O

Et2O

MeCN

PF6J. Barluenga, Angew. Chem. Int. Ed., 2001, 40, 3392.

(OC)5Cr

NMe2

Br

CO2Me

2 mol %Pd(OAc)2, Et3N

THF, reflux, 8 h, 80 %

O

CO2Me

Br

M. A. Sierra, J. Am. Chem. Soc., 2001, 123, 851 -861.

Louis S. Hegedus

William D. Wulff

Daniel F. Harvey Jose Barluenga

fischer carbenes

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