Transition-Metal-Free Synthesis of Ynones via Decarboxylative Alkynylation of α-Keto Acids under Mild Conditions

Abstract

A transition-metal-free synthetic method of various ynones via decarboxylative alkynylation of α-keto acids is described. The reaction is carried out under mild conditions and exhibits remarkable tolerance of functional groups. The mechanism of a radical process is proposed in the reaction.

Alkynylation of radicals: spotlight on the “Third Way” to transfer triple bonds

“…Similar valuable ynones were synthesized by Duan and coworkers upon the facile decarboxylation of α-keto acids under Li's oxidative conditions (eqn (2)) 39. Almost simultaneously, Xu and Feng documented the same transformation without silver catalyst 40. The decarboxylative alkynylation of aryl- and thio-difluoroacetic acids was also successful 41…”

α-Keto Acids: Acylating Agents in Organic Synthesis

“…Duan and co-workers and Feng, Xu, and co-workers have prepared a diversity of triorganylsilyl-protected ynones 151 and ynamides 152 in modest to very good yields by stirring a mixture of the keto acid 1 and the silyl-protected BI-alkyne 154 (1.2–1.5 equiv) in the presence of K 2 S 2 O 8 (0.6–0.7 equiv) in CH 3 CN/H 2 O (1:1) as the solvent at 50 °C for 12 or 24 h. In the case of the synthesis of ynamides 152 from the respective carbamoyl keto acids, it was necessary to use the addition of AgNO 3 (10 mol %) as a catalyst to promote the reaction in acceptable yields. Both protocols have proved to be general, despite the modest yields obtained in some cases, mainly starting from heteroaromatic glyoxylic acids (e.g., 151av , obtained in 31% and 45% yield, respectively). Interestingly, the sensitive ciano, aldehyde, acyl, and hydroxyl groups present in the phenyl ring of the BI-alkyne 154 or in the α-keto acids 1 were tolerated in the reaction, and the respective ynones 151q – s and 151au were obtained in 27%, 46%, 43%, and 29% yields .…”

“…Both protocols have proved to be general, despite the modest yields obtained in some cases, mainly starting from heteroaromatic glyoxylic acids (e.g., 151av , obtained in 31% and 45% yield, respectively). Interestingly, the sensitive ciano, aldehyde, acyl, and hydroxyl groups present in the phenyl ring of the BI-alkyne 154 or in the α-keto acids 1 were tolerated in the reaction, and the respective ynones 151q – s and 151au were obtained in 27%, 46%, 43%, and 29% yields . Similar to the light-promoted procedures described before, , the K 2 S 2 O 8 -promoted reactions were extended to alkylglyoxylic acids and aliphatic and aromatic BI-alkynes, with good outcomes, being an alternative to the photocatalytic decarboxylative alkynylation (Scheme ).…”

Metal-Free Method for Direct Synthesis of Functionalized β-Ketoenamines

“…For a long time, ynones 6 were mainly synthesized by transition metal-catalyzed couplings . But, this situation has been changed since some metal-free methods were developed in recent years . One of them was developed from our recent work as shown in Scheme : α-keto acid 1 and 1-iodoalkyne 2 initially was subjected to a BF 3 ·OEt 2 -catalyzed cyclization to give 4-iodo-5-hydroxy-furan-2-one 7 .…”