Diversity-Oriented Method Development: Multifunctional Homoallylic Amines and Azabicyclooctanes Bearing a Bridgehead Enamine

Two methods, designed primarily for applications in diversity-oriented synthesis (DOS), are introduced. The first is a Cu-H-catalyzed multicomponent process that involves a nitrile and a trisubstituted allenyl boronate. The first set of products are homoallylic α-secondary NH₂-amines, containing a trisubstituted alkenyl boronate, formed with >98% enantiospecificity, in up to >98:2 dr and as a single alkene isomer (>98% <i>Z</i>). The second method is efficient and diastereoselective triflic anhydride-mediated conversion of an unsaturated azapane-amide, generated from modification of the products of the foregoing catalytic process to azabicyclooctanes (ABCOs). The ABCOs contain a bridged enamine moiety and a trisubstituted alkene, which can be functionalized chemo- and stereoselectively. Accordingly, natural product-like rigid bicyclic frameworks can be obtained wherein four different fragments can be installed in space in a controllable fashion.