The intramolecular Heck reaction (IMHR) in chemistry is the coupling of an aryl or alkenyl halide with an alkene in the same molecule.
[2] Intramolecular variants of the reaction may be used to generate cyclic products containing endo or exo double bonds.
Additionally, in the presence of a chiral palladium catalyst, the intramolecular Heck reaction may be used to establish tertiary or quaternary stereocenters with high enantioselectivity.
[3] A number of tandem reactions, in which the intermediate alkylpalladium complex is intercepted either intra- or intermolecularly before β-hydride elimination, have also been developed.
[7] (3)Reactions involving palladium(II) acetate and phosphine ligands proceed by a third mechanism, the anionic pathway.
A similar anionic pathway is also likely operative in reactions of bulky palladium tri(tert-butyl)phosphine complexes.
β-Hydride elimination need not be the final step of the reaction, and tandem methods have been developed that involve the interception of palladium alkyl intermediates formed after migratory insertion by an additional reactant.
This section discusses the most common ring sizes formed by the intramolecular Heck reaction and some of its tandem and asymmetric variants.
In this and many other modes of intramolecular Heck cyclization, annulations typically produce a cis ring juncture.
[15] When dienes are involved in the intramolecular Heck reaction, insertion affords π-allylpalldium intermediates, which may be intercepted by nucleophiles.
[17] (10)The high functional group tolerance of the intramolecular Heck reaction allows it to be used at a very late stage in synthetic routes.
In a synthesis of (±)-FR900482, IMHR establishes a tricyclic ring system in high yield without disturbing any of the sensitive functionality nearby.
Alcohols have been shown to enhance catalyst stability in some cases,[25] and acetate salts are beneficial in reactions following the anionic pathway.