Conversion of carboxylic acids to nitriles using photoredox catalysis and benziodoxolone reagents: divergent mechanism when compared to alkynylation!

Fine-tuned organic photoredox catalysts are introduced for the metal-free alkynylation of alkylnitrile radicals generated via oxidative ring opening of cyclic alkylketone oxime ethers.

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...

We report the first decarboxylative alkynylation of the C‐terminus of peptides starting from free carboxylic acids. The reaction is fast, metal‐free, and proceeds cleanly to afford alkynylated peptides with a broad tolerance for the C‐terminal amino acid. By the use of hypervalent iodine reagents, the introduction of a broad range of functional groups was successful. C‐terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine‐tuned organic dyes.

This review explores the alkynylation of radicals as approach for the flexible and efficient synthesis of alkynes.

The development of catalytic chemical processes that enable the revalorization of nitrous oxide (N2O) is an attractive strategy to alleviate the environmental threat posed by its emissions1–6. Traditionally, N2O has been considered an inert molecule, intractable for organic chemists as an oxidant or O-atom transfer reagent, owing to the harsh conditions required for its activation (>150 °C, 50‒200 bar)7–11. Here we report an insertion of N2O into a Ni‒C bond under mild conditions (room temperature, 1.5–2 bar N2O), thus delivering valuable phenols and releasing benign N2. This fundamentally distinct organometallic C‒O bond-forming step differs from the current strategies based on reductive elimination and enables an alternative catalytic approach for the conversion of aryl halides to phenols. The process was rendered catalytic by means of a bipyridine-based ligands for the Ni centre. The method is robust, mild and highly selective, able to accommodate base-sensitive functionalities as well as permitting phenol synthesis from densely functionalized aryl halides. Although this protocol does not provide a solution to the mitigation of N2O emissions, it represents a reactivity blueprint for the mild revalorization of abundant N2O as an O source.

Ethynylbenziodoxolones (EBXs) are commonly used as radical traps in photocatalytic alkynylations. Herein, we report that aryl‐substituted EBX reagents can be directly activated by visible light irradiation. They act as both oxidants and radical traps, alleviating the need for a photocatalyst in several reported EBX‐mediated processes, including decarboxylative and deboronative alkynylations, the oxyalkynylation of enamides and the C−H alkynylation of THF. Furthermore, the method could be applied to the synthesis of alkynylated quaternary centers from tertiary alcohols via stable oxalate salts and from tertiary amines via aryl imines. A photocatalytic process using 4CzIPN as an organic dye was also developed for the deoxyalkynylation of oxalates.

A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol(on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones.