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Divergent Strain‐Release Amino‐Functionalization of [1.1.1]Propellane with Electrophilic Nitrogen‐Radicals
Author(s) -
Kim Ji Hye,
Ruffoni Alessandro,
AlFaiyz Yasair S. S.,
Sheikh Nadeem S.,
Leonori Daniele
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000140
Subject(s) - propellane , chemistry , radical , electrophile , amination , surface modification , photoredox catalysis , aniline , combinatorial chemistry , reactivity (psychology) , bicyclic molecule , photochemistry , organic chemistry , photocatalysis , catalysis , medicine , alternative medicine , pathology
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.