Enantioselective synthesis of (2R,3R)- and (2S,3S)-2-[(3-chlorophenyl)-(2-methoxyphenoxy)methyl]morpholine

The enantioselective synthesis of the (R,R)- and (S,S)-enantiomers of 1 from commercially available 3-chlorocinnamic acid is reported. The Sharpless asymmetric epoxidation was used to establish the stereocenters in the synthesis of both enantiomers of 1.

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(−)-(2S,3S)-[3-(3-Chlorophenyl)oxiranyl]methanolC9H9ClO2Ee = 82%[α]D = −24.1 (c 1.66, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 2S,3S

(−)-(2R,3R)-2-[(3-Chlorophenyl)-(2-methoxyphenoxy)methyl]morpholineC18H20ClNO3Ee ⩾ 92%[α]D = −6.8 (c 1.56, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 2R,3R