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Enantioselective Organocatalytic Synthesis of Bicyclic Resorcinols via an Intramolecular Friedel-Crafts-Type 1,4-Addition: Access to Cannabidiol Analogues.

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.

SUBMITTER: Bryant LA

PROVIDER: S-EPMC8457227 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Enantioselective Organocatalytic Synthesis of Bicyclic Resorcinols <i>via</i> an Intramolecular Friedel-Crafts-Type 1,4-Addition: Access to Cannabidiol Analogues.

Bryant Laura A LA Shankland Kenneth K Straker Hannah E HE Johnston Callum D CD Lees Nicholas R NR Cobb Alexander J A AJA

Advanced synthesis & catalysis 20210712 16

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 sh ...[more]

PMID: 34594164

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