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 K₂S₂O₈ 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.

中文翻译：

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末端炔烃的好氧和绿色 C-H 氰化

本研究描述了末端炔烃的良性 C-H 氰化，其中 α-氰酸酯作为无毒氰化物源。关键氰化铜中间体的原位生成是通过一系列 α-C-H 氧化和铜介导的 β-碳消除 α-氰酸酯，释放实验观察到的 α-酮酯副产物提出的。随后的氰化铜与末端炔烃的反应优先提供氰基炔烃，并超过了末端炔烃可能的 Glaser 型二聚或在质子条件下不希望的 HCN 积累。共氧化剂 K ₂ S ₂ O ₈的存在对这种选择性至关重要，可能是通过促进氧化转移金属化和由此形成的 Cu(III )(乙炔化物)(CN)中间体。使用的所有试剂和盐都是可商购的，便宜且无毒，避免使用氰化研究中通常需要的剧毒氰化物盐。该反应的范围用一组炔烃和 α-氰酸酯来证明。将该方法应用于雌酮衍生物末端炔基的后期功能化也是可行的，显示出其在药物设计中的实用价值。