Asymmetric syntheses of (-)-8-epi-swainsonine triacetate and (+)-1,2-di-epi-swainsonine. Carbonyl addition thwarted by an unprecedented aza-pinacol rearrangement

Hossein Razavi, Robin Polt

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Indolizidines (-)-8-epi-swainsonine triacetate and (+)-1,2-di-epi-swainsonine were synthesized from the O'Donnell Schiff base ester 1 derived from D-serine. Reductive-alkenylation of 1 with (i)Bu5-Al2H/H2C=CHMgBr followed by substrate-directed dihydroxylation of the pendant allylic group with OsO4, reduction of imine, and cyclization with Ph3P/CCl4 gave the polyhydroxylated pyrrolidines 8a and 8b as advanced intermediates. Efficient protecting group manipulations converted pyrrolidines 8a and 8b to their corresponding partially protected analogues 10a and 10b, which upon Swern oxidation and diastereoselective Keck-type allylation with BF3·Et2O afforded the required three-carbon homologues (10a, > 20:1 de; 10b, 3.5:1 de). Use of the chelating Lewis acid MgBr2 instead of BF3·Et2O with 10a led to a novel aza-pinacol rearrangement and allylation at the α-carbon to yield amino alcohol 17, which is similar to a hydride migration in the biosynthetic pathway of indolizidine alkaloids. Subsequent hydroboration, cyclization, and deprotection furnished (-)-8-epi-swainsonine triacetate 15a and (+)-1,2-di-epi-swainsonine 16b in good overall yields (6.3% for 1 → 15a, 13 steps, and 4.0% for 1 → 16b, 14 steps).

Original languageEnglish (US)
Pages (from-to)5693-5706
Number of pages14
JournalJournal of Organic Chemistry
Volume65
Issue number18
DOIs
StatePublished - Sep 8 2000

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Asymmetric syntheses of (-)-8-epi-swainsonine triacetate and (+)-1,2-di-epi-swainsonine. Carbonyl addition thwarted by an unprecedented aza-pinacol rearrangement'. Together they form a unique fingerprint.

  • Cite this