Divergent Strain‐Release Amino‐Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen‐Radicals. Issue 21 (26th February 2020)

• Record Type: Journal Article
• Authors: Kim, Ji Hye; Ruffoni, Alessandro; Al‐Faiyz, Yasair S. S.; Sheikh, Nadeem S.; Leonori, Daniele
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 21(2020)
• Page Start: 8225
• Page End: 8231
• Publication Date: 2020-02-26
• Subjects: amino-functionalization -- bioisosteres -- nitrogen radicals -- strain-release; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202000140
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Herein we report the development of a photocatalytic strategy for the divergent preparation of functionalized bicyclo[1.1.1]pentylamines. This approach exploits, for the first time, the ability of nitrogen‐radicals to undergo strain‐release reaction with [1.1.1]propellane. This reactivity is facilitated by the electrophilic nature of these open‐shell intermediates and the presence of strong polar effects in the transition‐state for C−N bond formation/ring‐opening. With the aid of a simple reductive quenching photoredox cycle, we have successfully harnessed this novel radical strain‐release amination as part of a multicomponent cascade compatible with several external trapping agents. Overall, this radical strategy enables the rapid construction of novel amino‐functionalized building blocks with potential application in medicinal chemistry programs as p ‐substituted aniline bioisosteres. Abstract : Electrophilic nitrogen‐radicals enable efficient strain‐release amino‐functionalization of [1.1.1]propellane. This radical reactivity can be used for the divergent assembly of 3‐substituted bicyclo[1.1.1]pentylamines, which are powerful aniline bioisosteres.