Copper-Catalyzed Aerobic Oxidative Coupling of Aromatic Alcohols and Acetonitrile to β-Ketonitriles

Abstract

A practical, convenient, and cheap copper-catalyzed aerobic oxidative coupling of aromatic alcohols and acetonitrile to β-ketonitriles has been developed. The green C-C bond formation involving the loss of two hydrogen atoms from the corresponding two carbons, respectively, unlocks opportunities for markedly different synthetic strategies.

Copper‐Catalyzed Cyanomethylation of Allylic Alcohols with Concomitant 1,2‐Aryl Migration: Efficient Synthesis of Functionalized Ketones Containing an α‐Quaternary Center

“…[8] On the other hand, although the formation of organometallic complexes (Ln, Rh, Fe, Ru) by activation of the a-CÀH bond of acetonitrile has been documented, [9] the synthetic use of nitriles is limited mainly to their enolate form, [10] the formation of which requires a strong base [pK a (MeCN) % 31.3, DMSO]. [11,12] We report herein a novel copper-catalyzed coupling reaction of allylic alcohols with alkyl nitriles that leads to ketones with the concomitant creation of an a-quaternary center (Scheme 1). [11,12] We report herein a novel copper-catalyzed coupling reaction of allylic alcohols with alkyl nitriles that leads to ketones with the concomitant creation of an a-quaternary center (Scheme 1).…”

Copper‐Catalyzed Intermolecular Carboetherification of Unactivated Alkenes by Alkyl Nitriles and Alcohols

“…(1), Scheme 1]. [11,12] In connection with our ongoing project on metal-catalyzed functionalization of carbon-carbon multiple bonds, [13] we have recently launched ar esearch program aimed at developing new processes that are initiated by copper-catalyzed direct coupling of alkenes with nitriles through the formation of aC sp 3 ÀC sp 3 bond. [9] Although formation of organometallic complexes (Ln, Rh, Fe,Ru) by activating the a-C À Hbond of acetonitrile has been documented, [10] the a-functionalization of nitriles is limited mainly to its enolate chemistry requiring astrong base [pK a (MeCN) % 31.3, DMSO] for its formation.…”

Copper‐Catalyzed Cyanomethylation of Allylic Alcohols with Concomitant 1,2‐Aryl Migration: Efficient Synthesis of Functionalized Ketones Containing an α‐Quaternary Center

“…We recently initiated a project aimed at the development of methods for the direct coupling of unactivated alkenes with alkyl nitriles and disclosed a copper-mediated/catalyzed oxyalkylation of unactivated alkenes with alkyl nitriles and amides/acids as reaction partners for the synthesis of functionalized phthalides, isochromanones, and g-lactones. [11,12] We report herein a novel copper-catalyzed coupling reaction of allylic alcohols with alkyl nitriles that leads to ketones with the concomitant creation of an a-quaternary center (Scheme 1). Although alkylation-induced 1,2-aryl migration has recently been reported for the conversion of allylic alcohols into ketones, [13] examples of the generation of homologated ketones with the creation of an a-quaternary center are rare.…”