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Stereoselective synthesis of cis-2,6-disubstituted piperidines from 1,2-cyclic sulfamidates

Author:
Eskici, Mustafa, Karanfil, Abdullah
Source:
Tetrahedron 2019 v.75 no.9 pp. 1214-1222
ISSN:
0040-4020
Subject:
acid hydrolysis, alanine, amines, chemical structure, diastereoselective synthesis, diastereoselectivity, hydrogenation, phenylalanine, piperidines, regioselectivity, valine
Abstract:
Diastereoselective synthesis of cis-2,6-disubstituted piperidines from 1,2-cyclic sulfamidates is described. Regioselective ring-opening reactions of 1,2-cyclic sulfamidates derived from L-phenylalanine, alanine, valine, norvaline with the ketal protected acetylide with a phenyl substituent proceed smoothly to form the N-sulfamate intermediates which on acidic hydrolysis give alkynylated amines with the ketal group intact. Hydrogenation of the alkynylated amines, debenzylation, ketal deprotection, subsequent cyclization (of aminoketones) and stereoselective hydrogenation of the cyclic iminium ion intermediates afford the corresponding cis-2,6-disubstituted piperidines in high diastereoselectivity (98% ≥ d.e.) with good chemical yields (68–86%). The present approach provides a novel route for the stereoselective synthesis of cis-2,6-disubstituted piperidines.
Agid:
6289910