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Enantioselective Organocatalytic Synthesis of Bicyclic Resorcinols via an Intramolecular Friedel−Crafts‐Type 1,4‐Addition: Access to Cannabidiol Analogues
Author(s) -
Bryant Laura A.,
Shankland Kenneth,
Straker Hannah E.,
Johnston Callum D.,
Lees Nicholas R.,
Cobb Alexander J. A.
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202100647
Subject(s) - chemistry , enantioselective synthesis , intramolecular force , bicyclic molecule , organocatalysis , resorcinol , yield (engineering) , friedel–crafts reaction , cannabidiol , organic chemistry , catalysis , combinatorial chemistry , stereochemistry , cannabis , materials science , metallurgy , psychology , psychiatry
Abstract The organocatalytic transformation of resorcinols is extremely rare. In this article, we report a highly enantioselective, organocatalytic intramolecular cyclization of these systems by a Friedel–Crafts‐type 1,4‐addition using a Jørgensen‐Hayashi‐like organocatalyst with a large silyl protecting group, and show that heat improves reaction yield with virtually no detriment to enantioselectivity. A variety of bicyclic resorcinols were obtained with excellent enantioselectivities (up to 94%). To show the utility of these constructs, and as part of a wider project involving the synthesis of cannabinoid‐like compounds, the resorcinol formed was used to generate both ‘normal’ and ‘abnormal’ cannabidiol (CBD) derivatives which were shown to have anticonvulsant activity.