Three‐Component Synthesis of α‐Amino‐α‐aryl Carbonitriles from Arynes, Aroyl Cyanides, and N,N‐Dimethylformamide

Abstract

A general and efficient synthesis of α‐amino‐α‐aryl carbonitriles through the three‐component reaction of arynes, aroyl cyanides, and DMF in a single step is described. DMF was not only used as the solvent, but it also participated in the reaction as a component. Used as the cyanide sources, the aroyl cyanides solved the toxicity and solubility problems associated with the use of HCN or metal cyanides in the Strecker synthesis. This procedure furnished α‐amino‐α‐aryl carbonitriles in moderate to good yields with broad substrate scope. Moreover, this reaction could be performed under mild conditions with high atom economy.

Recent Advances in Construction of C(sp2)–O Bonds via Aryne Participated Multicomponent Coupling Reactions

“…Inspired by the aforementioned progress, Wang, Lu, and co-workers used aroyl cyanides as the 3rd component in these MCRs to afford -amino--arylacetonitriles (Scheme 8). 21 In this transformation, the nucleophilic o-QMs react with benzoyl cyanides to form iminium salts that undergo cyanide group migration to produce the ,-difunctionalization products.…”

Synthesis of α-aminonitriles via a FeSO4-mediated oxidative cyanation of tertiary amines with benzoyl cyanide and molecular oxygen or TBHP

“…21 To our disappointment, no satisfied results were obtained from benzyl cyanide. By altering benzyl cyanide to benzoyl cyanide, 32 the yields changed drastically. The reaction of benzoyl cyanide with 1a in the presence of CuI and TBHP provided the desired cyanated product 2a in 36% yield ( …”

Recent Uses of N,N-Dimethylformamide and N,N-Dimethylacetamide as Reagents

“…All atoms of DMF were inserted in the polyfunctionalized compounds produced from domino reactions involving formation of arynes, cycloaddition with DMF and subsequent trapping with α-chloro β-diesters (Equation (90)) [ 22 ], aroyl cyanides (Equation (91)) [ 23 ] or diesters of acetylenedicarboxylic acid (Equation (92)) [ 24 ].…”

“…When uncertainty is expressed by the authors or suspected by us, the atom is typed in italic. Mechanistic schemes are not reported, but Scheme 2 [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] summarizes different proposed reactions of DM with the corresponding literature references, where DM acts as either a nucleophilic or electrophilic reagent, or leads to neutral, ionic or radical species. The review is divided in Sections depending on the DM fragment(s) which is (are) incorporated into the reaction product.…”