Nickel-Catalyzed Reductive Arylation of Redox Active Esters for the Synthesis of -Aryl Nitriles – Role of a Chlorosilane Additive

20 April 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A nickel-catalyzed reductive cross-coupling of redox-active N-hydroxyphthalimide (NHP) esters and iodoarenes for the synthesis of α-aryl nitriles is described. The NHP ester substrate is derived from cyanoacetic acid, which allows for a modular synthesis of substituted a-aryl nitriles, an important scaffold in pharmaceutical sciences. Mechanistic studies reveal that decarboxylation of the NHP ester to the reactive radical intermediate is accomplished by a combination of a chlorosilane additive and Zn dust. The reaction exhibits a broad scope as many functional groups are compatible under the reaction conditions, including complex highly functionalized medicinal agents.

Keywords

Nickel catalysis
reductive cross-coupling
chlorosilane
alpha-aryl nitrile
arylation
radical
NHP ester

Supplementary materials

Title
Description
Actions
Title
Rousseaux-RedoxCyanoAceticEster-Experimental-Procedures
Description
Actions
Title
Rousseaux-RedoxCyanoAceticEster-NMR-Spectra
Description
Actions

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