Enantioselective Synthesis of Alkyne-Substituted Quaternary Carbon Stereogenic Centers through NHC-Cu-Catalyzed Allylic Substitution Reactions with (i-Bu)2(Alkynyl)aluminum Reagents

摘要

A catalytic enantioselective method for the formation of alkyne-substituted all-carbon quaternary stereogenic centers is reported. Additions of alkynyialuminums to alkyl-, aryl-, carboxylic ester-, or silyl-substituted allylic phosphates are promoted by 1.0—5.0 mol% loadings of NHC-Cu complexes derived from air-stable and commercially available CuCl_2 • 2H_2O.The requisite Al-based reagents are prepared through treatment of the corresponding aryl-, heteroaryl-, alkyl-, or alkenyl-substituted terminal alkynes with diisobuty-laluminum hydride in the presence of 5.0 mol% Et_3N at ambient temperature. The desired 1,4-enynes are obtained in up to 98% yield and >99:1 enantiomeric ratio. Selected Au-catalyzed cydizations involving the alkyne unit of the enantio-merically enriched products are presented as a demonstration of the method's utility in chemical synthesis.