Construction of Chiral β-Trifluoromethyl Alcohols Enabled by Catalytic Enantioselective Aldol-Type Reaction of CF3CHN2

A zinc-/quinine-mediated enantioselective Aldol-type reaction of trifluorodiazoethane (CF3CHN2) with various aldehydes is described. This study demonstrated the feasibility of utilizing CF3CHN2 as an effective hard nucleophile in catalytic asymmetric transformations. Furthermore, the synthetic utility of this protocol is exemplified by the construction of a diverse set of chiral beta-trifluoromethylated alcohols, including a valuable HDAC inhibitor precursor.