Synthesis of Nitrile‐Bearing Quaternary Centers by an Equilibrium‐Driven Transnitrilation and Anion‐Relay Strategy

The efficient preparation of nitrile‐containing building blocks is of interest due to their utility as synthetic intermediates and their prevalence in pharmaceuticals. As a result, significant efforts have been made to develop methods to access these motifs which rely on safer and non‐toxic sources...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-07, Vol.58 (30), p.10300-10304
Main Authors: Alazet, Sébastien, West, Michael S., Patel, Purvish, Rousseaux, Sophie A. L.
Format: Article
Language:English
Subjects:
alkyl lithium reagents
alkyl nitriles
anion-relay strategy
Anions
Bearing
fragmentation
Intermediates
Lithium
Reagents
Synthesis
transnitrilation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The efficient preparation of nitrile‐containing building blocks is of interest due to their utility as synthetic intermediates and their prevalence in pharmaceuticals. As a result, significant efforts have been made to develop methods to access these motifs which rely on safer and non‐toxic sources of CN. Herein, we report that 2‐methyl‐2‐phenylpropanenitrile is an efficient, non‐toxic, electrophilic CN source for the synthesis of nitrile‐bearing quaternary centers by a thermodynamic transnitrilation and anion‐relay strategy. This one‐pot process leads to nitrile products resulting from the gem‐difunctionalization of alkyl lithium reagents. A one‐pot thermodynamic transnitrilation and anion‐relay strategy has been developed for the preparation of nitrile‐bearing quaternary centers from simple building blocks. This one‐pot transformation forms up to three new C−C bonds and involves transfer of a nitrile group from a non‐toxic cyanating reagent.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201903215