Three Type Of Carbene ComplexesCarbene complexes have formal metal-to-carbon double bonds. Several types are known. The reactivity of the carbene and how it contributes to the overall electron counting is dependent on the subtituents and metal involved.

Hartwig, Organotransition Metal Chemistry, 2010, pp 481–504.

LnMXR1

R2

Fischer carbenes

X = O, NR, SM = low-valent, middle or late transition metals• L-type ligand• donating 2 electrons

ElectrophilicNucleophilic

LnMR1

R2

Schrock carbenes

R1, R2 = alkyl or HM = high-valent carbyl or middle transition metals• 2X-type ligand (–2 charge)• donating 4 electrons

NucleophilicElectrophilic

LnMR1

EWG

Carbenoids

LnM = Rh2(O2CR)4, N4Ru, (N2O2)Ru, or (N,N)Cu• L-type ligand• donating 2 electrons

LnM C

Vinylidenes

R1, R2 = alkyl, aryl, or H• L-type ligand• donating 2 electrons

R1

R2Electrophilic

LnM

N-Heterocyclic carbenes

R = alkyl or aryl• generally a spectator ligand• L-type ligand• donating 2 electrons

NR

RN

Semmelhack, Organometallics in Synthesis, Schlosser, Ed., 2002, pp 1024–1041.

Fischer Carbenes

LnMXR1

R2

X = O, NR, SM = low-valent, middle or late transition metals

ElectrophilicNucleophilic

• Most developed carbenes are those of Cr, Mo, and W.• Usually synthesized from commerically available and stable M(CO)6.• Usually crystalline solids, easily purified by recrystallizaton or silica gel chromatography.• Air stable as solids, slight sensitive in solution. The stability is due to the heteroatom. Dialkyl complexes decompose at low temps.• The metal is d6 and zero valent, coordinateively saturated.

• To react at the metal, one of the carbonyls must be removed with high temps or photolysis.

(OC)5MR

OMe

M(0), d6, 18e–, sat.

(OC)4MR

OMe

M(0), d6, 16e–, unsat.

heat or hν(–CO) L

(OC)4MR

OMe

L

M

C

CC

CC

O

O

O

O

OR

OMe The "CO Wall" can destablize some complexes with α-branching on the R group.

PreparationPreparation of the Fischer carbene usually proceeds via an anionic acyl "ate" complex.

(OC)5Cr C ORLi

(OC)5Cr CO

RMe4NBr

(OC)5CrR

ONMe4

(ammonium salt)stable solid

("ate" complex)charge can be delocalized into all remaining carbonyl

groups

(OC)5CrR

OMe

stable solid

Me3OBF4

Alkyl lithium addition: probably most commonly used method

Reductive routes:

Cr(CO)6

K-C8 orNaNaph

Na2Cr(CO)5Cl

O

R(OC)5Cr C

OR (OC)5Cr

R

OMeMe3OBF4

R2N

O

R(OC)5Cr C

OR

NR2

Me3SiCl(OC)5Cr

R

NR2

Preparation

Vinylidene and allenylidiene intermediates: Neutral conditions

(CO)5Cr(thf)

(CO)6Cr

hνTHF

RC C(OC)5Cr

(an allenylidene)

OH

C(OC)5CrH

HO(a vinylidene)

(OC)5CrO

OH

MeOH

H

R

MeOH

(OC)5CrOMe

R

Addition Of Nucleophiles

(OC)5MOMe

R

The carbonyl groups are strongly electron withdrawing. This makes the M–C bond electrophilic. Reaction mechanisms are similar to the reactions of esters.

δ–δ+

Nuc(OC)5M

Nuc

R

δ–δ+ + MeO

(OC)5WOMe

Me

(OC)5WR

Me

(OC)5WOR

Me

(OC)5WSR

Me

(OC)5WNHBu

Me

RLi

MeS

NH2Bn

RO

CO Insertions and Carbometallations

With carbon-based nucleophiles or hydrides, the alkoxide can be slow to eliminate. The metal-based anion can then undergo other reactions. Carbonyl migrations and carbometallation of alkenes/alkynes are common. How facile these reactions are is quite dependent on the R group.

Eur. J. Org. Chem. 2004, 2471–2502.

(OC)5MOMe

(OC)5MR1 OMe

R1 (OC)4ML

L

O

OMeR1

L = CO, PR3

(OC)5MO OMe

R1

LH+

Me

O OMeR1 Low pressures of CO or the

presence of phosphines promotes the CO insertion.

Fischer Carbene "Enolates"

(OC)5MOR

The α-protons of Fischer carbenes are quite acidic (pKa ~12). Anionic bases needed for irreversible deprotonation. Weak bases (Pyr, DMAP, Et3N) can be used, but lead to formation of enol ether.

R

NR3(OC)5M

OR

R

H NR3(OC)5M

OR

R

H OR

RH

Anionic bases required for irreversible deprotonation. The "enolates" of alkoxycarbenes are only weakly nucleophilic, but can react with electrophiles in the presence of a Lewis acid.

(OC)5CrOMe

Me

1. BuLi, THF –78 ºC

2. TiCl4(OC)5Cr

O

Me

O Me

Organometallics 1991, 10, 807.

(OC)5CrOMe

Et

1. BuLi, Et2O –78 ºC

2. BF3•Et2O PhCHO

J. Am. Chem. Soc. 1985, 107, 503.

(OC)5Cr

OMe

Ph

OH

Me

Fischer Carbene "Enolates"The "enolates" of aminocarbenes are only more nucleophilic (compare ester enolates to amide enolates), and do not require Lewis acids to react.

J. Am. Chem. Soc. 1993, 115, 4602.

(OC)5CrNMe2

Me

1. BuLi, THF –78 ºC

2.O

(OC)5CrNMe2 O DMSO,

60 ºC, 71%

orDMDO, 78%

NMe2 OO

1. LDA, THF –78 ºC

2.O

Me

O

Me2N

O

Me2NOH

O

Me2N

O

+

> 95:5, 88%

(OC)5CrN

Me

MeO 1. BuLi, THF –78 ºC

2.(OC)5Cr

N

(S)(S)

MeO

O(S)(S)

O TfOH O

H

O

51% yield95% ee

Cycloadditions

(OC)5MOMe

α,β-Unsaturated Fischer carbenes undergo cycloaddition reactions but are much more reactive than the corresponding ester.

R

(OC)5MOMe

Me

Et3N, TMSCl

RCHO

RLi

M(CO)6

(OC)5MOMe

R

[4+2]

OEt

[2+2]

(OC)5MOMe

R

EtON N

TMS[3+2]

(OC)5MOMe

R

NNH

TMS

Conjugate Additions

(OC)5CrOEt

α,β-Unsaturated Fischer carbenes can also serve as Michael acceptors.

Ph

OLi

(OC)5CrOEt

PhO

anion "protects" carbene from further reactions

with nucleophilesMeLi

J. Am. Chem. Soc. 1992, 114, 2985.

Ph

(OC)5Cr

OEt HO MeOMe

HPh

(OC)5Cr

93% yield

OMe

HPh

98% yield

pyr

Removing the MetalThere are sevral methods available for removing the metal and converting the carbene into a different functional group.

(OC)5MXMe

R

Pyridine

OMe

R

CAN, DMDOR3NO, or DMSO

OXMe

RO

H

R

TfOH, or TFA

Bu3SnHpyr/hexane, 70ºC

Bu3SnOMe

R

CH2N2

OMe

RH2C

CyclopropanationFischer carbenes will react with electrophilic a olefins to form cyclopropanes. The yields can vary, but generally work well.

(OC)5MOMe

R1R2

R2 = CO2Me, CONMe2 CN, PO(OMe)2, SO2Ph, olefin

Δ

R2

R1OMe

Reaction is suppressed by CO pressure. This points to formation of a metallocyclobutane intermediate.

(OC)5MOMe

R1

R2(OC)4M

OMeR1

R2

(a metallocyclobutane)

R2

R1OMe

[2+2] R.E.

In order to cyclopropanate electron-rich olefins, acyloxycarbenes must be used. Likely involves a different (polar) mechanism.

(OC)5MOR2

R1

OR3

OR3

R1OAc

OR2 = OAc

OR3

OR2 = OMe

(OC)4MOR3

HOMe

R1

+

CyclopropanationNeutral alkenes are usually poor substrates, but can react in an intramolecular sense. More complex alcohols can be introduced using acyloxycarbenes (triflates would be difficult to handle/prepare).

(OC)5CrONMe4

Ph HO

1. RCOCl

2.(OC)5M

O

Ph OPh

HΔ

(OC)5CrONMe4

Ph

Cl

O

Me

CH2Cl2, –10 ºC to rtO

O

PhH

Me53% yield

88% yield

Reactions with alkynes are more facile than with alkenes, but gives an α,β-unsaturated carbene. This can go on and do other chemistry.

(OC)5MOMe

R1

(OC)4MOMe

R1

R2

(a metallocyclobutene)

R2

R2

M(CO)4

MeO R1

(a vinylogousFischer carbene)

Dötz ReactionReaction of alkenyl and aryl alkoxycarbenes with alkynes produces highly substituted benzene rings or quinones, depending on work-up conditions.

(OC)5CrOMe RSRL

Δ, –CO(OC)4Cr

RSRL

MeO

RL

(CO)4Cr

RS

OMe

CO insertion

RL

C

RS

OMe

O

Cr(CO)4

Cr-vinyl ketene

RL

RS

OMeCr(CO)4

Oairhν

RL

RS

OMe

HO

get quinone with CANThe intermediates in this process can be intercepted by other functional groups before the final ring closure, leading to cascade processes and complex products.

(OC)4Cr

O

RL

RSOMeCO insertion

Cr-Bound KetenesThe formation of Cr-bound ketenes can be used to explain a number of synthetic transformations. The ease of formation appears to be dependent on the substitution around the carbene and can be promoted by photochemical means (in the visible). The process of inserting CO is quite reversible and, unless trapped, will deinsert CO and return to the carbene.

(OC)4CrXR

RCO

hν (OC)4Cr

O

XR

R (OC)4CrCO

RX R

The ketene is generated in low concentrations and is metal-bound. This prevents many of the side reactions commonly encountered with ketenes. The reactivity pattern still mimics that of normal ketenes.

(OC)4CrCO

RX R1RN R2

NR

R1

RX

O

R2O R2

ZnCl2O

R1

RX

O

R2

R2

R1

RX

O

R2ROH

OR

ORX

R1

RNH2

NHR

ORX

R1