Cu-Catalyzed Three-Component Carbofunctionalization of 1,3-Dienes
Vincent R. Viviani, Travis L. Buchanan, An T. Ho, John A. Little, Andrei G. Popov, Matthew Barnett, Kira Q. McMahon, Samuel N. Gockel, Kami L. Hull
Abstract
The carboamination of 1,3-dienes provides direct and efficient access to allylic amines in a step-economical fashion. Herein, we disclose a three-component 1,3-diene carboamination reaction that provides modular access to a multitude of allylic amines. A representative scope of 1,3-dienes, activated alkyl halides, and amines is demonstrated to serve as components for this reaction, with yields ranging from up to 96%. High regioisomeric ratios are observed with both substituted and unsubstituted diene derivatives for either 1,2- or 1,4-carboamination (≥12:1). Mechanistic investigations demonstrate that the reaction proceeds via atom transfer radical addition to the diene, affording an isolable allylic halide intermediate. The scope was expanded to a general carbofunctionalization, by adding an exogenous O, S, P, or C nucleophile and base to the reaction upon formation of the allylic halide, in a two-step, one-pot process.