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Coordination Assisted Distal C−H Alkylation of Fused Heterocycles
Author(s) -
Ramakrishna Kankanala,
Biswas Jyoti Prasad,
Jana Sadhan,
Achar Tapas Kumar,
Porey Sandip,
Maiti Debabrata
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201907544
Subject(s) - benzothiazole , benzoxazole , chemistry , alkylation , thiazole , quinoline , covalent bond , surface modification , combinatorial chemistry , catalysis , nitrile , stereochemistry , substrate (aquarium) , alkyne , organic chemistry , oceanography , geology
Distal C−H bond functionalization of heterocycles remained extremely challenging with covalently attached directing groups (DG). Lack of proper site for DG attachment and inherent catalyst poisoning by heterocycles demand alternate routes for site selective functionalization of their distal C−H bonds. Utilizing non‐productive coordinating property to hold the heterocycle into the cavity of a template system in a host–guest manner, we report distal C−H alkylation (C‐5 of quinoline and thiazole, C‐7 of benzothiazole and benzoxazole) of heterocycles. Upon complexation with heterocyclic substrate, nitrile DG in template directs the metal catalyst towards close vicinity of the specific distal C−H bond of the heterocycles. Our hypothesized pathway has been supported by various X‐ray crystallographically characterized intermediates.