Applications of conformational design: rational design of chiral ligands derived from a common chiral source for highly enantioselective preparations of (R)- and (S)-enantiomers of secondary alcohols

A pair of diastereomers 7 and 8 were easily synthesized in only two steps from a single common chiral source according to the concept of conformation design. The efficiency of these chiral ligands was evaluated by their application to the asymmetric addition of diethylzinc to aldehydes. This catalytic asymmetric process afforded the a most efficient access to the (R)- and (S)-enantiomers of a given secondary alcohol with similarly outstanding enantioselectivities and high yields. Our results also showed that the control of the desired conformer’s population by conformation design is a new and practical strategy for the rational and precise design of highly enantioselective chiral ligands for metal-catalyzed reactions. The mechanism and possible transition states for the catalytic asymmetric addition have been proposed on the basis of previous studies as well as the crystal structure of the chiral ligands 7 and 8.

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Diphenyl-(l-((1S)-phenylethyl)aziridin-(2R)-yl)-methanolC23H23NO[α]D20=-50.4 (c 0.660, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (S,2R)

Diphenyl-(l-((1S)-phenylethyl)aziridin-(2S)-yl)-methanolC23H23NO[α]D20=-49.0 (c 0.502, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (S,2S)