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Rapid Access to Azabicyclo[3.3.1]nonanes by a Tandem Diverted Tsuji-Trost Process.

ABSTRACT: A three-step synthesis of the 2-azabicyclo[3.3.1]nonane ring system from simple pyrroles, employing a combined photochemical/palladium-catalysed approach is reported. Substrate scope is broad, allowing the incorporation of a wide range of functionality relevant to medicinal chemistry. Mechanistic studies demonstrate that the process occurs by acid-assisted C-N bond cleavage followed by ?-hydride elimination to form a reactive diene, demonstrating that efficient control of what might be considered off-cycle reactions can result in productive tandem catalytic processes. This represents a short and versatile route to the biologically important morphan scaffold.

SUBMITTER: Steeds HG

PROVIDER: S-EPMC7702095 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Rapid Access to Azabicyclo[3.3.1]nonanes by a Tandem Diverted Tsuji-Trost Process.

Steeds Hannah G HG Knowles Jonathan P JP Yu Wai L WL Richardson Jeffery J Cooper Katie G KG Booker-Milburn Kevin I KI

Chemistry (Weinheim an der Bergstrasse, Germany) 20201006 63

A three-step synthesis of the 2-azabicyclo[3.3.1]nonane ring system from simple pyrroles, employing a combined photochemical/palladium-catalysed approach is reported. Substrate scope is broad, allowing the incorporation of a wide range of functionality relevant to medicinal chemistry. Mechanistic studies demonstrate that the process occurs by acid-assisted C-N bond cleavage followed by β-hydride elimination to form a reactive diene, demonstrating that efficient control of what might be considere ...[more]

PMID: 32812670

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