Cyanoalkylation: Alkylnitriles in Catalytic CC Bond‐Forming Reactions

Abstract

Alkylnitriles are one of the most ubiquitous nitrogen-containing chemicals and are widely employed in reactions which result in nitrile-group conversion into other functionalities. Nevertheless, their use as carbon pronucleophiles in carbon-carbon bond-forming reactions has been hampered by difficulties associated mainly with the catalytic generation of active species, that is, α-cyano carbanions or metalated nitriles. Recent investigations have addressed this challenge and have resulted in different modes of alkylnitrile activation. This review illustrates these findings, which have set the foundation for the development of practical and conceptually new catalytic, direct cyanoalkylation methodologies.

Atmosphere‐Controlled Chemoselectivity: Rhodium‐Catalyzed Alkylation and Olefination of Alkylnitriles with Alcohols

“…Nitriles are useful buildingb locks in organic synthesis. [8] With watera st he only by-product,t he alkylation of alkylnitriles with alcohols through hydrogen borrowing provides a" green" route for the synthesis of new nitrile compounds.T ransition-metal catalysts, including Ru, [3,9] Os, [10] Ir, [11] Rh, [12] and Pd, [13] have been employed for this reaction. The olefination of alkylnitriles with alcohols could afford a,b-unsaturated nitriles, which are also valuable intermediates in organic synthesis.…”

Palladium-catalyzed ligand-promoted site-selective cyanomethylation of unactivated C(sp3)–H bonds with acetonitrile

“…The cyanomethylation of organic molecules is of great research interest to organic and medicinal chemists due to the wide presence of the cyano group in biologically active molecules and the facile conversion of the cyano group into many other functional groups, such as amides, esters, aldehydes, and primary amines 1. A variety of different synthetic strategies have been developed for the selective introduction of the cyanomethyl group 2.…”

Iron‐Catalyzed Alkylation of Nitriles with Alcohols

“…They can be easily transformed into ap lethora of compounds, for example,a mides, carboxylic acids, ketones, and oxazolines (Scheme 1). [1] Moreover,t here are many drugs and natural products containing cyano groups. [2] Amongst the methodsf or the synthesis of nitrile compounds,t he a-alkylationo fa lkyl nitriles with alcohols through ah ydrogen-borrowing or hydrogen auto-transfer strategy [3] provides an environmentally benign route, with water as the only by-product.…”