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

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 facilit...

Full description

Saved in:
Bibliographic Details
Published inAngewandte Chemie International Edition Vol. 59; no. 21; pp. 8225 - 8231
Main Authors Kim, Ji Hye, Ruffoni, Alessandro, Al‐Faiyz, Yasair S. S., Sheikh, Nadeem S., Leonori, Daniele
Format Journal Article
LanguageEnglish
Published WEINHEIM Wiley 18.05.2020
Wiley Subscription Services, Inc
John Wiley and Sons Inc
EditionInternational ed. in English
Subjects
Amination
amino-functionalization
Aniline
bioisosteres
Chemistry
Chemistry, Multidisciplinary
Construction
Free radicals
Intermediates
Nitrogen
nitrogen radicals
Physical Sciences
Radicals
Science & Technology
strain-release
nitrogen radicals
POTENT
REDUCTION
ALKYL
amino-functionalization
bioisosteres
HYDROAMINATION
strain-release
Online AccessGet full text

Cover

More Information
Summary: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. 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.
Bibliography:These authors contributed equally to this work.
UKRI
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202000140