In organic synthesis, ligand-modified copper(I) hydride (CuH) complexes have become well-known reagents and catalysts for selective reduction, particularly toward Michael acceptors and carbonyl compounds. Recently, our group and others have found that these hydride complexes undergo migratory insertion (hydrocupration) with relatively unactivated and electronically unpolarized olefins, producing alkylcopper intermediates that can be leveraged to forge a variety of useful bonds. The resulting formal hydrofunctionalization reactions have formed the basis for a resurgence of research in CuH catalysis. This Account chronicles the development of this concept in our research group, highlighting its origin in the context of asymmetric hydroamination, evolution to more general C-X bond-forming reactions, and applications in the addition of olefin-derived nucleophiles to carbonyl derivatives.Hydroamination, the formal insertion of an olefin into the N-H bond of an amine, is a process of significant academic and industrial interest, due to its potential to transform widely available alkenes and alkynes into valuable complex amines. We developed a polarity-reversed strategy for catalytic enantioselective hydroamination relying on the reaction of olefins with CuH to generate chiral organocopper intermediates, which are intercepted by electrophilic amine reagents. By engineering the auxiliary ligand, amine electrophile, and reaction conditions, the scope of this method has since been extended to include many types of olefins, including challenging internal olefins. Further, the scope of amine reagents has been expanded to enable the synthesis of primary, secondary, and tertiary amines as well as amides, N-alkylated heterocycles, and anilines. All of these reactions exhibit high regio- and stereoselectivity and, due to the mild conditions required, excellent tolerance for heterocycles and polar functional groups.Though the generation of alkylcopper species from olefins was originally devised as a means to solve the hydroamination problem, we soon found that these intermediates could react efficiently with an unexpectedly broad range of electrophiles, including alkyl halides, silicon reagents, arylpalladium species, heterocycles, and carbonyl derivatives. The general ability of olefins to function as precursors for nucleophilic intermediates has proved particularly advantageous in carbonyl addition reactions because it overcomes many of the disadvantages associated with traditional organometallic reagents. By removing the need for pregeneration of the nucleophile in a separate operation, CuH-catalyzed addition reactions of olefin-derived nucleophiles feature improved step economy, enhanced functional group tolerance, and the potential for catalyst control over regio- and stereoselectivity. Following this paradigm, feedstock olefins such as allene, butadiene, and styrene have been employed as reagents for asymmetric alkylation of ketones, imines, and aldehydes.
