C C Bond Formation

CHEM 261: Organic Chemistry II

CarbonCarbon Bond Forming Reactions

To form the carbon skeletons of complex molecules, organic chemists need an extensive repertoire of carboncarbon bond forming reactions.

(1) Organocuprate coupling reactions,

(2) Suzuki reaction,

(3) Heck reaction, (4) Dihalocarbene addition reaction,

(5) Simmons-Smith reaction.

Coupling Reactions of Organocuprates

Organocuprate reagents react with a variety of functional groups including acid chlorides, epoxides and ,-unsaturated carbonyl compounds. Organocuprate reagents also react with organic halides RX to form coupling products RR that contain a new CC bond. Only one R group of the organocuprate is transferred to form the product, while the other becomes part of the RCu, a reaction product.

General Features of Organocuprate Coupling Reactions

Methyl, 1, cyclic 2, vinyl, and aryl halides can be used. Reactions with vinyl halides are stereospecific. The halogen (X) may be Cl, Br, or I. Tertiary (3) halides are too sterically hindered to react.

Suzuki Reactions

The Suzuki reaction is a palladium-catalyzed coupling of an organic halide (RX) with an organoborane (RBY2) to form a product (RR) with a new CC bond. Pd(PPh3)4 is the typical palladium catalyst. The reaction is carried out in the presence of a base such as NaOH or NaOCH2CH3. Vinyl or aryl halides are most often used, and the halogen is usually Br or I. The Suzuki reaction is completely stereospecific.

Examples of the Suzuki Reaction

The Heck Reaction

The Heck reaction is a Pd-catalyzed coupling of a vinyl or aryl halide with an alkene to form a more highly substituted alkene with a new CC bond. One H atom of the alkene starting material is replaced by the R group of the vinyl or aryl halide. Palladium(II) acetate [Pd(OAc)2] in the presence of a triarylphosphine [P(o-tolyl)3] is the typical catalyst. The reaction is carried out in the presence of a base such as triethylamine.

Examples of the Heck Reaction

Carbenes and Cyclopropane Synthesis:

A carbene, R2C:, is a neutral reactive intermediate that contains a divalent carbon surrounded by six electrons: the lone pair, and two each from the two R groups.

Carbenes and Cyclopropane Synthesis:

Dihalocarbenes, :CX2, are especially useful reactive intermediates since they are readily prepared from trihalomethanes (CHX3) by reaction with strong base.

Examples of the Dihalocarbene Reaction

The Simmons-Smith Reaction:

Non-halogenated cyclopropanes can be prepared by the reaction of an alkene with di-iodo-methane, CH2I2, in the presence of a copperactivated zinc reagent called zinc-copper couple [Zn(Cu)]. This is known as the Simmons-Smith reaction. The reaction is stereospecific.

Mechanism of Simmons-Smith