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Enantioenriched Methylene‐Bridged Benzazocanes Synthesis by Organocatalytic and Superacid Activations
Author(s) -
Beaud Rodolphe,
Michelet Bastien,
Reviriot Yasmin,
MartinMingot Agnès,
Rodriguez Jean,
Bonne Damien,
Thibaudeau Sébastien
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201912043
Subject(s) - stereocenter , organocatalysis , superacid , enantioselective synthesis , iminium , chemistry , methylene , combinatorial chemistry , stereoselectivity , michael reaction , stereochemistry , catalysis , organic chemistry
Achieving in a straightforward way the synthesis of enantioenriched elaborated three‐dimensional molecules related to bioactive natural products remains a long‐standing quest in organic synthesis. Enantioselective organocatalysis potentially offers a unique opportunity to solve this problem, especially when combined with complementary modes of activation. Here, we report the sequential association of organocatalytic and superacid activations of simple linear achiral readily available precursors to promote the formation of unique highly elaborated chiral methylene‐bridged benzazocanes exhibiting three to five fully‐controlled stereocenters. This peculiar backbone, difficult to assemble by standard synthetic approaches, is closely related to bioactive natural and synthetic morphinans and benzomorphans. The formation of a highly reactive chiral 7‐membered ring N ‐acyl iminium superelectrophilic ion, evidenced by low‐temperature in situ NMR experiments, triggers a challenging stereoselective Friedel–Crafts‐type cyclization.