The mechanism of nickel-catalyzed couplings of an enone, alkyne, and organozinc has been studied. Adducts of the substrates with nickel(0) have been isolated and characterized, and their reactivity was examined. A potential intermediate was demonstrated to not be kinetically competent in catalytic cyclizations. A computational approach employing the B3LYP density functional method and the 6-31G(d) basis set was used to examine mechanistic possibilities that were consistent with experimental observations, and a modified mechanism for the catalytic cyclizations was formulated. The newly proposed mechanism involves production of an active catalyst that involves a novel interaction between Ni(0) and dimethylzinc.

Two metallacycles derived from the oxidative cyclization of nickel(0) with an alkynyl enal have been isolated and fully characterized. The metallacycles obtained possess an η 1 nickel O-enolate motif within the metallacyclic framework.

[reaction: see text] 1,3-Dienes were prepared by a variety of nickel-catalyzed couplings and cyclization processes. Intermolecular or partially intramolecular couplings of alkynes, vinylzirconium reagents, and either aldehydes or enones efficiently proceeded to generate a broad range of functionalized dienes.

A new strategy for effecting cascade cyclization processes using nickel enolates has been developed. Nickel enolates may be cleanly generated by the oxidative cyclization of an enal and alkyne with Ni(0), and the resulting enolate may be functionalized by a variety of alkylation processes. Partially and fully intramolecular versions of the process allow the rapid synthesis of complex polycyclics from simple achiral, acyclic precursors.

[structure: see text] The first total synthesis and stereochemical definition of isodomoic acid G has been achieved. The key nickel-catalyzed coupling of an alkynyl enone with an alkenylzirconium allows formation of the pyrrolidine ring and most of the stereochemical features in a single step. This report provides the first total synthesis application of this new reaction and illustrates its utility in the stereoselective preparation of highly substituted 1,3-dienes.