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 β-keto esters, β-nitrostyrenes, and α,β-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. (Figure presented.).