A Site- and Stereoselective Intermolecular Alkene-Alkyne Coupling Process

摘要

Intermolecular coupling reactions that proceed through carbon-carbon (C-C) bond formation are central to modern organic chemistry.[1] The subset of these reactions that proceed through site- and stereoselective coupling of substituted bonds (C-C, C-C) typically require the unsaturated unit(s) to be electronically activated or sterically differentiated. In our efforts to identify highly selective metal-mediated pathways for coupling unactivated and differentially functionalized systems, we recently defined a regioselective and stereospecific intermolecular coupling reaction of differentially functionalized internal alkynes that proceeds via Group 4 metallacyclopentadienes.[2] The corresponding intermolecular coupling reaction between an unactivated polysubstituted alkene and an internal alkyne represents a potentially more significant and correspondingly more difficult problem.[3], [4] This mode of coupling is complicated by: 1) the lower reactivity of the CC bond in reactions with metal-carbon bonds, 2) the stability of the intermediate metallacyclopentenes, and 3) the potential of generating numerous regio- and stereoisomeric products A-D (Scheme 1).[5], [6] In fact, aside from the classical cycloaddition reactions, intermolecular CC bond formation through site- and stereoselective functionalization of unactivated, polysubstituted olefins has eluded organic chemists.[3] A general means to accomplish this transformation with high regio- and stereocontrol would define a versatile new bond construction for organic synthesis (Scheme 1).