A
carbometallation is any reaction where a carbon-metal bond reacts with a carbon-carbon
Pi bond to produce a new carbon-carbon
Sigma bond and a carbon-metal σ-bond.
The resulting carbon-metal bond can undergo further carbometallation reactions (oligomerization or polymerization see Ziegler-Natta polymerization) or it can be reacted with a variety of
including halogenating reagents,
Carbonyl group, oxygen, and inorganic salts to produce different organometallic reagents. Carbometallations can be performed on
and
to form products with high geometric purity or
Enantiomer, respectively. Some metals prefer to give the
anti-addition product with high selectivity and some yield the syn-addition product. The outcome of
syn and
anti- addition products is determined by the mechanism of the carbometallation.
Carboboration
Carboboration is one of the most versatile carbometallation reactions. See
Carboboration.
Carboalumination
The carboalumination reaction is most commonly catalyzed by zirconocene dichloride (or related catalyst). Some carboaluminations are performed with
titanocene complexes.
This reaction is sometimes referred to as the
ZACA reaction (ZACA) or the Zr-catalyzed methylalumination of alkynes (ZMA).
The most common trialkyl aluminium reagents for this transformation are trimethylaluminium, triethylaluminium, and sometimes triisobutylaluminium. When using reagents that have beta-hydrides, eliminations and hydroaluminium reactions become competing processes. The general mechanism of the ZMA reaction can be described as first the formation of the active catalytic species from the pre-catalyst zirconocene dichloride through its reaction with trimethyl aluminium. First
transmetalation of a methyl from the aluminium to the zirconium occurs. Next, chloride abstraction by aluminium creates a
Ion zirconium species that is closely associated with an anionic aluminium complex. This zirconium cation can coordinate an alkene or alkyne where migratory insertion of a methyl then takes place. The resultant vinyl or alkyl zirconium species can undergo a reversible, but stereoretentive
transmetalation with an organoaluminium to provide the carboalumination product and regeneration of the zirconocene dichloride catalyst. This process generally provides the syn-addition product; however, conditions exist to provide the anti-addition product though a modified mechanism.
Trimethylsilyl (TMS) protected alkynes, trimethyl germanium alkynes, and Alkyne can produce anti-carboalumination products at room temperature or elevated temperatures if a coordinating group is nearby on the substrate.
Carbolithiation
Carbolithiation is the addition of an organolithium reagent across a carbon-carbon pi-bond. The organolithium reagents used in this transformation can be commercial (such as
N-Butyllithium) or can be generated through
deprotonation or lithium-halogen exchange.
Both inter- and intramolecular examples of carbolithiation exist and can be used in synthesis to generate complexity. Organolithiums are highly reactive chemicals and often the resulting organolithium reagent generated from the carbolithiation can continue to react with electrophiles or remaining starting material (resulting in
polymerization).
This reaction has been rendered enantioselective
through the use of
sparteine, which can
Chelation the lithium ion and induce chirality.
Today, this is not a common strategy due to a shortage of natural sparteine. However, recent advances in the synthesis of sparteine surrogates and their effective application in carbolithiation have reactivated interest in this strategy.
Another demonstration of this reaction type is an alternative route to tamoxifen starting from diphenylacetylene and organolithium:
As a consequence of the high reactivity of organolithiums as strong bases and strong
, the substrate scope of the carbolithiation is generally limited to chemicals that do not contain
or
Electrophile .
Carbomagnesiation and carbozincation
Due to the decreased
Nucleophile of
(organomagnesium) and organozinc reagents, non-catalyzed carbomagnesiation and carbozincation reactions are typically only observed on activated or strained alkenes and alkynes.
For example,
Polar effect groups like
esters,
or
must be in conjugation with the carbon-carbon π-system (see
Michael reaction) or a directing group like an alcohol or
amine must be nearby to direct the reaction. These reactions can be catalyzed by a variety of transition metals such as iron,
copper,
zirconium,
nickel,
cobalt
and others.
Illustrative is the Fe-catalyzed reaction of with phenylmagnesium bromide, which generates a vinyl magnesium intermediate. Hydrolysis affords the diphenylalkene:[In this reaction the Grignard reagent combines with iron acetylacetonate and tributylphosphine to give an ill-defined aryliron intermediate, which then reacts with copper(I) chloride an intermediate organocopper.]
Carbopalladation
Carbopalladations can be a description of the elementary step of a reaction catalyzed by a palladium catalyst (
Heck reaction)
and can also refer to a carbometalation reaction with a palladium catalyst (alkene difunctionalization,
hydrofunctionalization,
or
reductive Heck)
