Synthesis of 4-(R)-naphthalene-2-yloxy-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(R)-ol and 4-(S)-naphthalen-2-yloxy-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(S)-ol: Versatile chiral intermediates for synthesis

摘要

A convenient and rapid synthesis of 4-(R)-(naphthalen-'2-yloxy)-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(R)-ol and 4-(S)-(naphthalen-2-yloxy)-1-(1-phenyl-(S)-ethyl)-pyrrolidin-3-(S)-ol is disclosed. The reaction scheme is highlighted by the meso-epoxidation of 1-(1-phenyl-(S)-ethyl)-2,5-dihydro-1H-pyrrole followed by addition of 2-naphthol alkoxide to provide both expected diastereoisomers. Separation of the diastereoisomers by crystallization provided access to both diastereoisomers in modest yield without the employment of expensive chiral catalysts. X-ray analysis of one of the diastereoisomers led to the unambiguous assignment of each diastereoisomer. These chiral pyrrolidine analogues should be useful as intermediates in natural product, combinatorial/ parallel synthesis, and medicinal chemistry.