Recyclable Organocatalysts for a One-Pot Asymmetric Synthesis of 2-Fluorocyclohexanols Bearing Six Contiguous Stereocenters

A recyclable fluorous bifunctional Cinchona alkaloid/thiourea-catalyzed quadruple fluorination/ Michael/Michael/aldol sequence has been developed for the one-pot synthesis of cyclohexanols bearing six contiguous stereocenters including a fluorinated tertiary carbon. By using readily available starting materials including beta-keto esters, beta-nitrostyrenes, and alpha, beta-unsaturated aldehydes, fully functionalized cyclohexanols were synthesized in 52-80% yields with up to 99% ee and > 20: 1 dr. The fluorous catalyst could be easily recovered by fluorous solid-phase extraction in 94-97% yield and > 98% purity. In addition to the high synthetic efficiency achieved through the pot economic reactions, other green techniques such as transition metal-free catalysis and catalyst recovery are also employed.