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Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals.

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.

SUBMITTER: Kim JH

PROVIDER: S-EPMC7318212 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Divergent Strain-Release Amino-Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen-Radicals.

Kim Ji Hye JH Ruffoni Alessandro A Al-Faiyz Yasair S S YSS Sheikh Nadeem S NS Leonori Daniele D

Angewandte Chemie (International ed. in English) 20200226 21

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 reduct ...[more]

PMID: 32003916

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