Copper-catalyzed stereoselective addition reactions using olefins

The nucleophilic addition of allyl fragments to carbonyl compounds and their derivatives is among the most reliable and frequently utilized transformations in organic synthesis. However, most existing methods rely on stoichiometric organometallic reagents, which are wasteful, cumbersome to prepare, and intolerant of many functional groups. We describe an alternative strategy that involves the mild and chemoselective generation of allylmetal species in situ from olefins, followed by catalyst-controlled selective addition within the same catalytic cycle. First, we demonstrate the allylation of imines, which can be used to prepare either the linear or branched isomer of useful homoallylic amine products. Notably, the regioselectivity is perfectly controlled by the choice of nitrogen protecting group. Next, we report the diastereo- and enantioselective allylation of ketones, a difficult class of electrophiles for traditional asymmetric allylation reactions. All of these transformations tolerate a variety of protic and electrophilic functional groups, as well as medicinally relevant heterocyclic substituents. Finally, we discuss the mechanistic basis for these transformations and their selectivity, relying both on nuclear magnetic resonance (NMR) experiments and density functional theory (DFT) calculations.