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Diastereoselective Synthesis of α‐Hydroxy‐ and α‐Aminoindolizidines and ‐quinolizidines. Evidence for a Novel Cyclization/Hydride Migration Mechanism in the TiCl 4 ‐Induced Reaction of Prolinal Benzylimines by Deuterium Labeling Studies
Author(s) -
Laschat Sabine,
Grehl Matthias
Publication year - 1994
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19941271027
Subject(s) - chemistry , hydride , lewis acids and bases , piperidine , diastereomer , isopropyl , stereochemistry , cationic polymerization , carbenium ion , medicinal chemistry , aldehyde , organic chemistry , catalysis , hydrogen
Lewis acid‐catalyzed cyclization of prolinal and 2‐piperidine‐carbaldehyde benzylimines 11, 12 results in the diastereoselective formation of α‐amino‐β‐alkyl‐substituted indolizidines 15, 17, 19, 21 and ‐quinolizidines 16, 18, 20 , respectively. Both diastereoselectivity and constitution depend on the Lewis acid. FeCl 3 yields α,β‐ trans ‐α‐(benzylamino)‐β‐isopropenyl derivatives 15 and 16 , probably by a cationic cyclization via carbenium ions 32a, b. In contrast, TiCl 4 yields α,β‐ cis ‐α‐(benzylideneamino)‐β‐isopropyl derivatives 19 and 20 by a novel cyclization/intermolecular hydride transfer mechanism, which was supported by deuterium labeling studies. Compounds 15, 16, 19 , and 20 were converted to the diastereomeric acetamides 24, 25 and 28, 29 . By an analogous cyclization of the aldehydes 8 and 9 only α,β‐ cis ‐α‐hydroxy‐β‐isopropenylindolizidines 51 and ‐quinolizidines 52 were obtained irrespective of the Lewis acid used. The structures of 30 and 52 were elucidated by X‐ray analysis.