Base‐Promoted Addition of Arylacetonitriles to Terminal Alkynes: Regio‐ and Stereoselective Access to Disubstituted Acrylonitriles

Abstract

A base‐promoted nucleophilic addition of arylacetonitriles to terminal alkynes has been described for the first time, providing a simple and straightforward protocol for the synthesis of a range of structurally diverse (Z)‐2,3‐disubstituted acrylonitriles in moderate to excellent yields. Of particular note, the transition metal‐free carbon‐carbon double bond forming reaction is regio‐ and stereoselective under mild conditions. A variety of functional groups can be tolerated on both the arylacetonitrile substrate and the alkyne coupling partner. Moreover, the reaction is easily scalable and the products thus obtained can serve as versatile intermediates for the synthesis of a series of useful substances.magnified image

Manganese Catalyzed α-Olefination of Nitriles by Primary Alcohols

“…Traditional syntheses of α,β-unsaturated nitriles involve Knoevenagel condensation of aldehydes and arylacetonitriles in the presence of stoichiometric or catalytic bases . However, base mediated condensation reactions have several drawbacks: self-condensation of the nitriles, aldol reaction of the carbonyl group bearing enolizable α-hydrogens, Cannizzaro reaction, potential attack of aldehyde (bearing α-hydrogen) by the nitrile, and poor tolerance of a wide range of functional groups toward base. , Alternative reagents and catalysts are also reported for the condensation of aldehydes and nitriles, including several other routes to obtain α,β-unsaturated nitriles. , However, most of them suffer from toxicity issues, expensive starting reagents, poor yield, limited accessibility of starting materials, and generation of copious waste.…”

Synthesis of Acrylonitriles via Mild Base Promoted Tandem Nucleophilic Substitution‐Isomerization of α‐Cyanohydrin Methanesulfonates

“…[ 15 ] However, these methods usually suffer from poor substrate scope and/or low E / Z selectivity. Recently, Jiang and coworkers reported an efficient base promoted addition of arylacetonitriles to terminal alkynes [ 16 ] (Scheme 1f), providing a straightforward and transition metal‐free protocol for the preparation of acrylonitriles although strong base (KO t Bu) was needed. On the other hand, Pd catalyzed Suzuki cross‐coupling of organoboronic acids with α‐cyanohydrin triflates has been reported by Falck and coworkers (Scheme 1g).…”

Synthesis of 1-Cyano-3-acylnaphthalenes via Formal [4+2] Benzannulation of 2-(2-Alkynylphenyl)acetonitriles and Alkynones

“…Subsequently, the new intermediate C could be generated by intramolecular cyclization. Usually, carbon anion could attack the triple bond of the terminal alkyne . However, this is a rare example wherein carbon anion directly adds to the triple bond of internal alkyne without electron-withdrawing group in absence of transition metal or Lewis acids .…”