Racemic Vinylallenes in Catalytic Enantioselective Multicomponent Processes

Abstract

Chapter 1. Development of NHC–Cu Complex Catalyzed Enantioselective Multicomponent Reactions involving Racemic Vinylallene, B2(pin)2 and α,β,γ,δ-Unsaturated Diester We have developed a broadly applicable protocol for converting a variety of vinylallenes to multifunctional allyl moieties followed by diastereo-, and enantioselective 1,6-conjugate addition to α,β,γ,δ-unsaturated diesters. Through just one operation, products bearing vicinal stereogenic centers, a Z-trisubstituted alkenyl–B(pin) unit, a vinyl group, a β,γ-unsaturated diester moiety were generated in up to 67% yield, 87:13 Z:E ratio, >98:2 d.r., and 98:2 e.r. Reactions were readily catalyzed by 5.0 mol % of an amino-alcohol derived NHC–Cu complex at ambient temperature, and involved a vinylallene, B2(pin)2, an α,β,γ,δ-unsaturated diester. Versatility and utility of the products were demonstrated by a variety of chemoselective modifications, involving the β,γ-unsaturated diester moiety, vinyl, and alkenyl–B(pin) unit, to access vitamin D3 side chain. Insights on the dynamic behavior of intermediated Cu–allyl species and accounts for various selectivity profiles were outlined by mechanistic experiments and DFT based stereochemical models. Chapter 2. Bisphosphine–Cu Complex Promoted Diastereo-, Enantioselective Additions of Boron-Containing Multifunctional Allyl Moieties to Ketones Racemic vinylallenes are fascinating substrates for catalytic multicomponent processes, due to their ability to form multifunctional allyl moieties. Specifically, an approach for diastereo-, and enantioselective addition to readily available ketones, enones and diennones has been developed. Reactions involving a racemic vinylallene, B2(pin)2, and ketone were promoted by 3.0-5.0 mol % of a commercially available bisphosphine–Cu complex at ambient temperature, furnishing products that contain an easily functionalizable vinyl moiety, an alkenyl–B(pin) containing Z-trisubstituted homoallylic alcohol with vicinal stereogenic centers in up to 83% yield, >98:2 Z:E ratio, >98:2 d.r., and 97:3 e.r. Applicability and flexibility of this method is highlighted by chemoselective modifications involving the alkenyl–B(pin) and vinyl unit to obtain a 5-norstemmadenine monoterpenoid indole alkaloid (+)-16-hydroxy-16,22-dihydroapparicine. These studies foreshadow the use of vinylallenes as starting materials to generate structurally unique allyl species in a wide range of multicomponent transformations.