Access to 2,6-Disubstituted 4‑Oxopiperidines Using a 6‑Endo-trig Cyclization: Stereoselective Synthesis of Spruce Alkaloid and (+)-241D

A synthetic route to cis-2-methyl-4-oxo-6-alkylpiperidines has been developed using a 6-endo-trig cyclization of (E)-enones. The base-mediated intramolecular cyclization was found to be general for both alkyl- and aryl-substituted enones, providing the corresponding 4-oxopiperidines in high yields (...

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Bibliographic Details
Published in:Journal of organic chemistry 2018-01, Vol.83 (1), p.535-542
Main Authors: Harkiss, Alexander H, Sutherland, Andrew
Format: Article
Language:English
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Summary:A synthetic route to cis-2-methyl-4-oxo-6-alkylpiperidines has been developed using a 6-endo-trig cyclization of (E)-enones. The base-mediated intramolecular cyclization was found to be general for both alkyl- and aryl-substituted enones, providing the corresponding 4-oxopiperidines in high yields (80–89%). Stereoselective reduction of the 2,6-cis-disubstituted 4-oxopiperidines then gave the 2,4,6-cis,cis-trisubstituted 4-hydroxypiperidines in high diastereoselectivity. The general nature of this approach was demonstrated with the synthesis of the natural products, spruce alkaloid and (+)-241D.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.7b02799