Room‐Temperature Decarboxylative Alkynylation of Carboxylic Acids Using Photoredox Catalysis and EBX Reagents

Abstract

Alkynes are used as building blocks in synthetic and medicinal chemistry, chemical biology and materials science. Therefore, efficient methods for their synthesis are the subject of intensive research. Herein, we report the synthesis of alkynes directly from broadly available carboxylic acids at room temperature under visible light irradiation. The combination of an iridium photocatalyst with EthynylBenziodoXolone (EBX) reagents allowed the decarboxylative alkynylation of carboxylic acids in good yields under mild conditions. The method could be applied to the transfer of silyl-, aryl-and alkyl-substituted alkynes. It was especially successful in the case of -amino and -oxo acids derived from the biomass.Alkynes are among the most versatile functional groups in synthetic chemistry, as they are sufficiently stable, yet reactive enough to be easily modified. These properties made them ideally suited for applications not only in organic synthesis, but also in chemical biology and materials science (Scheme 1).[1] All potential applications remain tributary of an efficient synthesis of alkynes. In particular, the metalcatalyzed Sonogashira cross-coupling is now broadly applied to access acetylenes (Scheme 1, A).[2] However, the Sonogashira reaction requires starting materials functionalized with adequate leaving groups, which themselves need to be introduced into the molecules. New approaches are urgently needed to make the synthesis of structurally diverse alkynes more efficient. To meet this challenge, the direct alkynylation of SP 2[3] or SP 3[4] C-H bonds has been intensively investigated in the last decade (Scheme 1, B). Nevertheless, many of these methods still suffer from harsh conditions, limited scope and the need for directing groups or adjacent heteroatoms to control the selectivity in C-H functionalization. Scheme 1. Synthesis and applications of alkynes.As an alternative to classical cross-coupling or C-H functionalization, decarboxylative methods have recently attracted strong interest (Scheme 1, C).[5] Indeed, the required carboxylic acids starting materials are derived from the biomass, and are therefore often even cheaper than the corresponding C-H compounds. Furthermore, the carboxy group allows controlling the site of functionalization and only carbon dioxide is generated as waste. Despite these advantages, examples of decarboxylative alkynylation of aliphatic carboxylic acids are rare (Scheme 2). In 2009, Chao-Jun Li and co-workers reported the decarboxylative alkynylation of amino acids using a copper catalyst and di-tert-butyl peroxide as stoichiometric oxidant at 110 °C (Scheme 2, A). [6] In 2010, Seidel and co-workers [7] and Chao-Jun Li and coworkers [8] used the condensation of aldehydes or ketones instead of the peroxide oxidant (Scheme 2, B). The copper-catalyzed method was extended to -cyano carboxylic acids by Xu and co-workers in 2013 using alkynyl bromides (Scheme 2, C).[9] Finally, in 2012, Chaozhong Li and co-workers reported a different approach based on the oxidative...

Photoredox Catalysis in Organic Chemistry

“…In addition, a wide range of α-amino, α-oxy, benzylic, and simple alkyl radicals can be accessed using this strategy, with the carboxylic acid acting as a traceless activation handle. As a result, carboxylic acids have been exploited in a variety of redox-neutral transformations including decarboxylative fluorinations, 35 vinylations, 36 alkynylations, 37 and conjugate additions 38 as well as enabling hydrodecarboxylation 39 and radical–radical coupling reactions (Scheme 7). 40 Synthetic chemists have rapidly adopted the strategies discussed in this section as functionalized amine products are valuable pharmacophores.…”

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…Finally, both catalytic cycles are closed by a dimetallic SET event in which the Ni I species acts as an electron acceptor to regenerate the Ir III and Ni 0 catalysts. In 2015, the Xiao [39] and Waser [40] groups independently reported the radical decarboxylative alkynylation of alkyl carboxylic acids with ethynylbenziodoxolone derivatives 16 (Scheme 8). Remarkably, their procedures were almost identical and differed only in the choice of base (CsOBz vs. Cs 2 CO 3 ).…”

Recent Advances on Diverse Decarboxylative Reactions of Amino Acids

“…Alkynes are important chemical structures and synthetic intermediates, and the construction of alkyl‐substituted alkynes is highly desirable. Waser's group reported a decarboxylative alkynylation of free carboxylic acids ( 6 and 126 ) by using visible light photoredox catalysis at room temperature in the presence of only an iridium photocatalyst (Scheme ) . α‐Amino acids could be converted to the corresponding alkynes 128 in good yields.…”