Catalyst-Directed Guidance of Sulfur-Substituted Enediolates to Stereoselective Carbon–Carbon Bond Formation with Aldehydes

A highly chemo-, regio-, and stereoselective
glycolate aldol reaction
of sulfur-substituted enediolates with aldehydes was developed by
employing a l-cyclohexylglycine-derived chiral iminophosphorane
as a catalyst. The key for establishing this protocol is the distinct
ability of the iminophosphorane catalyst to precisely direct the equilibrium
mixture of the enediolates toward the intermolecular carbon–carbon
bond formation with simultaneous yet rigorous control of relative
and absolute stereochemistry. The critical importance of the cyclohexyl
substituents on the catalyst backbone in dictating the reaction pathway
and the stereochemical outcome was elucidated through an extensive
quantum analysis by density functional theory calculations.