Enantioselective, catalytic carbon-carbon bond-forming reactions.

摘要

Enantioselective, catalytic conjugate additions of carbon nucleophiles to alpha,beta-unsaturated carbonyl compounds are described. In the presence of a chiral aluminum complex, malononitrile and alpha-cyanoacetates participate in Michael reactions with unsaturated ketone and N-benzoyl imide electrophiles. The scope of this process with respect to beta-substitution of the electrophile is broad, encompassing a range of aliphatic and aromatic groups. Synthetic applications of the resulting gamma-cyanocarbonyl compounds, including the preparation of enantioenriched piperidines, are discussed. Vicinal stereocenters are generated with high diastereo- and enantioselectivity by reactions of substituted cyanoacetate nucleophiles.*; Catalytic, enantioselective transformations of N-acyliminium ion intermediates are described. Chiral thiourea 7d mediates acylative Pictet-Spengler reactions of imines derived from tryptamines and aliphatic aldehydes. Substituted tetrahydro-beta-carboline derivatives, useful building blocks for indole alkaloid synthesis, are obtained in high enantiomeric excess. Catalyst optimization studies and the solid-state structure of 7d are presented. Acylative Mannich reactions of isoquinolines with silyl ketene acetals are also catalyzed by thiourea 7d, resulting in the formation of enantioenriched dihydroisoquinoline products from readily available, aromatic feedstocks. The observation that N-acyliminium ions are activated by a chiral hydrogen bond donor raises questions regarding the nature of the interaction between these species. Experimental and computational studies investigating the possible participation of neutral, chloroamide intermediates are discussed.*; *Please refer to dissertation for diagrams.