Regioselective Nickel‐Catalyzed Reductive Couplings of Enones and Allenes

Abstract

Catalytic reductive coupling processes have been developed in numerous contexts as a strategy for the regioand stereoselective installation of alkenes. The direct coupling of a polar p system with a relatively nonpolar p system is often a successful strategy for selectively accomplishing synthetically desirable heterocouplings while avoiding undesired homocoupling of either reagent. For example, reductive couplings of aldehydes, enones, enals, or imines paired with alkynes, alkenes, or allenes have been extensively developed in recent years. Processes of this type are often highly effective in controlling both the position and stereochemistry of di-, tri-, and tetrasubstituted alkenes within polyfunctional molecules. Among these methods, the preparation of g,dunsaturated carbonyl groups by nickeland cobalt-catalyzed processes has been the subject of considerable study. The catalytic strategies developed for synthesis of g,d-unsaturated carbonyl groups by the coupling of two p-containing components include enone–alkyne additions in work reported by our group and by Cheng and co-workers, and enone–alkene additions in work reported by Jamison and co-workers, and Ogoshi et al. (Scheme 1). Processes of this type provide an important counterpart to organocuprate technology and hydrometallative processes, while having the advantage of not requiring the stoichiometric preparation of an alkenyl metal species. Stereodefined trisubstituted alkenes 1, trans-disubstituted alkenes 2, and monosubstituted alkenes 3 may be readily prepared by the above-mentioned enone–alkyne and enone– alkene coupling processes. However, a general strategy for the preparation of 1,1-disubstituted alkenes 4 by these methods has not been developed. Since terminal alkyne reductive coupling strategies and hydrometallative processes typically favor formation of the conjugate addition product 2 with a 1,2-disubstituted alkene, the 1,1-disubstituted alkene 4 is considerably more difficult to prepare. As depicted below (Scheme 2), regiocontrolled reductive coupling of an