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Chemoenzymatic Synthesis of All Four Diastereomers of 2,6‐Disubstituted Piperidines through Stereoselective Monoamination of 1,5‐Diketones
Author(s) -
Simon Robert C.,
Zepeck Ferdinand,
Kroutil Wolfgang
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201202793
Subject(s) - stereoselectivity , diastereomer , piperidine , regioselectivity , chemistry , intramolecular force , stereochemistry , ring (chemistry) , lewis acids and bases , organic chemistry , catalysis
The regioselectivity of various enantiocomplementary ω‐transaminases was evaluated for the stereoselective monoamination of designated 1,5‐diketones; excellent conversions, enantio‐ and regioselectivities were observed. The resulting amino‐ketones underwent spontaneous intramolecular ring closure to afford Δ1‐piperideines, which served as precursors for the cis ‐ and anti ‐piperidine scaffold as demonstrated for the synthesis of the alkaloids dihydropinidine and epi ‐dihydropinidine. Key to the success of accessing the trans ‐piperidines was a Lewis acid mediated conformational change of the Δ1‐piperideines in the reduction step. Thus, all four diastereomers of 2,6‐disubstituted piperidines could successfully be prepared.