An aerobic and green C–H cyanation of terminal alkynes. Issue 45 (10th November 2020)

• Record Type: Journal Article
• Authors: Zhu, Peng-Fei; Si, Yi-Xin; Zhang, Song-Lin
• Is Part Of: Organic & biomolecular chemistry. Volume 18:Issue 45(2020)
• Page Start: 9216
• Page End: 9220
• Publication Date: 2020-11-10
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d0ob01928c
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : This study reports the C–H cyanation of terminal alkynes with α-cyanoacetates serving as a readily available and friendly cyano source under Cu/O2 conditions. Abstract : This study describes a benign C–H cyanation of terminal alkynes with α-cyanoesters serving as a nontoxic cyanide source. In situ generation of the key copper cyanide intermediate is proposed by a sequence of α-C–H oxidation and copper-mediated β-carbon elimination of α-cyanoesters, releasing the α-ketoester byproduct observed experimentally. The ensuing reaction of copper cyanide with terminal alkynes delivers preferentially cyanoalkynes and surpasses the possible Glaser type dimerization of terminal alkynes or the undesired accumulation of HCN under protic conditions. The presence of the co-oxidant K2 S2 O8 is crucial to this selectivity, probably by promoting oxidative transmetalation and the resulting formation of the Cu(iii )(acetylide)(CN) intermediate. All the reagents and salts used are commercially available, cheap and nontoxic, avoiding the use of highly toxic cyanide salts typically required in cyanation studies. The scope of this reaction is demonstrated with a set of alkynes and α-cyanoesters. The application of this method to late-stage functionalization of the terminal alkyne group in an estrone derivative is also feasible, showing its practical value for drug design.