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Highly Chemoselective Synthesis of Indolizidine Lactams by SmI 2 ‐Induced Umpolung of the Amide Bond via Aminoketyl Radicals: Efficient Entry to Alkaloid Scaffolds
Author(s) -
Shi Shicheng,
Lalancette Roger,
Szostak Roman,
Szostak Michal
Publication year - 2016
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.201602717
Subject(s) - umpolung , chemistry , chemoselectivity , quinolizidine , amide , combinatorial chemistry , reactivity (psychology) , functional group , stereochemistry , organic chemistry , nucleophile , alkaloid , catalysis , medicine , polymer , alternative medicine , pathology
Samarium(II) iodide enables a wide range of highly chemoselective umpolung radical transformations proceeding by electron transfer to carbonyl groups; however, cyclizations of important nitrogen‐containing precursors have proven limited due to their prohibitive redox potential. Herein, we report the first reductive cyclizations of unactivated cyclic imides onto N‐tethered olefins using SmI 2 /H 2 O. This new umpolung protocol leads to the rapid synthesis of nitrogen‐containing heterocycles that are of particular significance as precursors to pharmaceutical pharmacophores and numerous classes of alkaloids. The reaction conditions tolerate a wide range of functional groups. Excellent chemoselectivity is observed in the cyclization over amide and ester functional groups. Such unconventional reactivity has important implications for the design and optimization of new bond‐forming reactions by umpolung radical processes. The reaction advances the SmI 2 cyclization platform to the challenging unactivated N‐tethered acyl‐type radical precursors to access nitrogen‐containing architectures.