Catalytic Enantioselective Allylation of Imines and Trifluoroketones Using New and Underutilized Organoboron Reagents

Thesis advisor: Amir H. HoveydaA general method for the catalytic enantioselective addition of silylallenes to phosphinoyl aldimines has been developed. Reactions are promoted in the presence of 5.0 mol% of an N–heterocyclic carbene–copper complex and a silyl-protected propargyl boron reagent. The reaction is efficient, requiring only 10 minutes, highly group selective, enantioselective and products can be further functionalized. Utility is highlighted in the total synthesis of marine alkaloid (S)-(–)-cyclooroidin using our product as a key intermediate in the total synthesis. The catalytic enantioselective addition of a 1,3-butadiene has been developed using a homoallenylboron reagent. These transformations are promoted by a C1-symmetric N–heterocyclic carbene–copper complex within 4 hours. Products can be obtained with gamma selectivity to afford the diene containing product. Efforts have been expanded towards the application of our product as a key intermediate towards the total synthesis of (+)-homochelidonine. Key transformations include a highly selective 1,2-protoboration of the 1,3-diene product followed by a Pd-catalyzed intramolecular sp2-sp3 Suzuki cross coupling. The development of a general catalytic enantioselective method for the propargyl addition to trifluoroketones has been studied. Reactions are complete within 15 minutes, broadly applied to alkyl-, alkenyl, alkynyl, aryl, and heteroaryl-substituted trifluoroketones, highly enantioselective and group selective. Key findings include use of an aminophenol containing an electron-withdrawing to improve reactivity and enantioselectivities. The method can be carried out on gram scale and has been applied to a substrate which can be elaborated towards glucocorticoid agonist BI 653048.Thesis (PhD) — Boston College, 2017.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry