Stereocontrolled synthetic routes to various syn-β-amino alcohol derivatives

Abstract

Stereocontrolled synthetic routes to various syn-β-amino alcohol derivatives were accomplished. Bis(trichloroacetimidate) prepared in situ from 3-buten- 1,2-diol was subjected to iodocyclization to yield dihydro-1,3-oxazine cis-44e with 93% diastereomeric excess, which was transformed into a variety of syn-b- amino alcohols 154a-f via aziridine 153. Efficient syntheses of statine and its analogues were attained from aziridine diols R-149 and S-149, which were prepared via iodocyclization of trichloroacetimidates of chiral 3-buten-1,2-diols R-136 and S-136. Olefinic diols 190 and 203 were iodocyclized to provide dihydro-1,3-oxazine 196a and oxazolidine 206a with 90 and 93% de, respectively, which were served as the precursors of various $C_2$ symmetric and meso-amino alcohols. $C_2$ Symmetric and meso-iodo hydroxy ammonium chlorides generated from 196a and 206a were cyclized under basic conditions to produce various heterocycles chemoselectively, which comprise tetrahydrofurans 214 and 228, piperidines 220, 222 and 230, and pyrrolidines 224 and 225. For the synthesis of a key intermediate to 1β-methylcarbapenem antibiotics, aziridine 233 was prepared from alcohol 234 via iodoamination. Regioselective opening reaction of 233 with cyanide provided 255a, which has the requisite four contiguous chiral centers. But conversion of nitrile 255a into azetidinone carboxylic acid 155 was not achieved.