Synthesis of Enantiomerically Enriched 2-Substituted Pyrrolidine Analogues of Norhygrine. Applicatin of the Hetero-Diels-Alder Addition of Sulfur Dioxide

Abstract

The Vogel's reaction cascade (one-pot hetero-Diels-Alder addition of SO 2 , ionization of the sultines into zwitterions and their quenching by electron-rich alkenes) has been applied to the preparation of enantiomerically-enriched (1S)-2((2R)-l-benzoylpyrrolidin-2-yl)pentan-3-one (14). Reaction of SO 2 with (-)-(1E',3Z)-2-methyl-1-((1S')-1-phenylethoxy)penta-1,3-dien-3 -ol benzoate (5: derived from (S)-1-phenylethanol (97% ee)) and allyltrimethylsilane in the presence of a Lewis acid at -78°C provides (-)-(2Z,1'S,45,55)-4-methyl-5-(l'-phenylethoxy)octa-2,7-dien-3-ol benzoate (9). Selective cleavage of the benzyl ether of 9 and subsequent S N 2 displacement with Ph 2 P(O)N 3 provided an azide 11 that was converted into 14.