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Mannich‐type Reactions of Cyclic Nitrones: Effective Methods for the Enantioselective Synthesis of Piperidine‐containing Alkaloids
Author(s) -
Lisnyak Vladislav G.,
LynchColameta Tessa,
Snyder Scott A.
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201809799
Subject(s) - piperidine , enantioselective synthesis , chemistry , mannich reaction , combinatorial chemistry , catalysis , ring (chemistry) , organic chemistry , stereochemistry
Even though there are dozens of biologically active 2‐substituted and 2,6‐disubstituted piperidines, only a limited number of approaches exist for their synthesis. Herein is described two Mannich‐type additions to nitrones, one using β‐ketoacids under catalyst‐free conditions and another using methyl ketones in the presence of chiral thioureas, which can generate a broad array of such 2‐substituted materials, as well as other ring variants, in the form of β‐ N ‐hydroxy‐aminoketones. Both processes have broad scope, with the latter providing products with high enantioselectivity (up to 98 %). The combination of these methods, along with other critical steps, has enabled 8‐step total syntheses of the 2,6‐disubstituted piperidine alkaloids (−)‐lobeline and (−)‐sedinone.