Photocatalytic decarboxylation of free carboxylic acids and their functionalization.

Visible light mediated decarboxylative functionalization of carboxylic acids and their derivatives has recently emerged as a novel and powerful toolkit for small molecule activation in diverse carbon-carbon and carbon-hetero bond forming reactions. Naturally abundant highly functionalized bench-stable carboxylic acid analogs have been employed as promising alternatives to non-trivial organometallic reagents for mild and eco-benign synthetic transformation with traceless CO2 by-products. In this highlight article, we focus on the development of various photodecarboxylative functionalization strategies along with intra/inter-molecular cyclization via concerted single electron transfer (SET) or energy transfer (ET) pathways. Moreover, widely explored carboxylic acids are systematically classified here into four categories; i.e., α-keto, aliphatic, α,ß-unsaturated, and aromatic analogs for a concise overview to the readership. The association of decarboxylative radical species with coupling partners to construct C-C and C-N/O/S/P/X bonds for each analogous acid has been presented in brief.

Merging Photocatalytic Doubly-Decarboxylative Csp 2 -Csp 2 Cross-Coupling for Stereo-Selective (E)-α,ß-Unsaturated Ketones Synthesis.

A photocatalytic domain of doubly decarboxylative Csp 2 -Csp 2 cross coupling reaction is disclosed. Merging iridium and palladium photocatalysis manifested carbon-carbon bonds in a tandem dual-radical pathway. Present catalytic platform efficiently cross-coupled α, ß-unsaturated acids and α-keto acids to afford a variety of α, ß-unsaturated ketones with excellent (E)-selectivity and functional group tolerance. Mechanistically, photocatalyst implicated through reductive quenching cycle whereas cross coupling proceeded over one electron oxidative pallado-cycle.

Base-Promoted Tandem Pathway for Keto-Amides: Visible Light-Mediated Room-Temperature Amidation Using Molecular Oxygen as an Oxidant.

Herein, we report metal- and photocatalyst-free room-temperature amidation for α-ketoamide synthesis from feedstock phenacyl bromides and amines using molecular oxygen as an oxidant as well as a source of oxygen in the amide segment. Visible light-mediated base-promoted one-pot sequential C-N/C═N/C═O bond formation takes place in a tandem manner to afford the desired product. Functional group tolerance (benzylic alcohol, keto, cyano, nitro, halo, etc.), a broad substrate scope, and gram-scale synthesis make this synthetic methodology more attractive. We have observed that electron-rich aromatic amines, aliphatic amines, and phenacyl bromide derivatives proceeded the present transformation with marginally superior reactivity in comparison to electron-deficient aromatic amines and phenacyl bromide derivatives. Moreover, several control experiments, in situ isolation of secondary amine and imine as key intermediates, and 18O-labeling experiments provide complete insight into the mechanism of the tandem pathway.

Pd-Catalyzed Tandem Pathway for Stereoselective Synthesis of (E)-1,3-Enyne from ß-Nitroalkenes by Using a Sacrificial Directing Group.

The involvement of nitroalkenes instead of minimal one alkyne motif for (E)-1,3-enynes synthesis through a palladium catalyzed stereoselective bond forming pathway at room temperature is presented. Implication of nitro group as a sacrificial directing group, formation of magical alkyne on a newly developed Csp 3 -Csp 3 bond with initial palladium-MBH adduct make this methodology distinctive. This protocol features an unprecedented sequential acetate addition, carbon-carbon bond formation, isomerization of double bond and nitromethane degradation in a tandem catalytic walk via dancing hybridization. Mechanistic understanding through identification of intermediates and computational calculations furnishes complete insight into the tandem catalytic pathway. Broad substrates scope and functional groups tolerance make this synthetic methodology magnificent and dynamic. This represents the first example of stereoselective 1,3-enyne synthesis exclusively from alkene substrates by introducing the concept of sacrificial directing group.

Merging Photocatalytic C-O Cross-Coupling for α-Oxycarbonyl-ß-ketones: Esterification of Carboxylic Acids via a Decarboxylative Pathway.

Herein, the first merged photocatalytic pathway for the C-O cross-coupled esterification of carboxylic acids to α-oxycarbonyl-ß-ketones has been demonstrated. Decarboxylation of α,ß-unsaturated acids promotes the formation of the ß-ketone fragment of the desired product. Water as the source of oxygen for the ketone segment and aerial oxygen as an oxidant make the present synthetic methodology green and sustainable. This new C═O and C-O bond-forming methodology takes place in a cascade manner under a dual Ir/Pd-catalytic pathway, with the liberation of H2O and CO2 as the only byproducts.

Room-Temperature Synthesis of 1,3,5-Tri(het)aryl Benzene from Nitroalkenes Using Pd(OAc)2: Complete Mechanistic and Theoretical Studies.

Herein, a room-temperature catalytic pathway for 1,3,5-tri(het)aryl derivatives from nitroalkenes using simple Pd(OAc)2 is presented. This newly developed C-C bond-forming methodology takes place in a cascade manner with the initial pallado-Morita-Baylis-Hillman (MBH) type adduct. The broad substrate scopes, functional group tolerance, and different aryl-substituted benzene derivatives make this methodology more attractive. Furthermore, the mechanistic understanding through isolation of intermediates and DFT studies of the catalytic cycle provide requisite insight into the methodology.

Tandem Acceptorless Dehydrogenative Coupling-Decyanation under Nickel Catalysis.

The development of new catalytic processes based on abundantly available starting materials by cheap metals is always a fascinating task and marks an important transition in the chemical industry. Herein, a nickel-catalyzed acceptorless dehydrogenative coupling of alcohols with nitriles followed by decyanation of nitriles to access diversely substituted olefins is reported. This unprecedented C═C bond-forming methodology takes place in a tandem manner with the formation of formamide as a sole byproduct. The significant advantages of this strategy are the low-cost nickel catalyst, good functional group compatibility (ether, thioether, halo, cyano, ester, amino, N/O/S heterocycles; 43 examples), synthetic convenience, and high reaction selectivity and efficiency.

Nickel-Catalyzed Guerbet Type Reaction: C-Alkylation of Secondary Alcohols via Double (de)Hydrogenation.

Acceptorless double dehydrogenative cross-coupling of secondary and primary alcohols under nickel catalysis is reported. This Guerbet type reaction provides an atom- and a step-economical method for the C-alkylation of secondary alcohols under mild, benign conditions. A broad range of substrates including aromatic, cyclic, acyclic, and aliphatic alcohols was well tolerated. Interestingly, the C-alkylation of cholesterol derivatives and the double C-alkylation of cyclopentanol with various alcohols were also demonstrated.

General Synthesis of N-Alkylation of Amines with Secondary Alcohols via Hydrogen Autotransfer.

Direct catalytic N-alkylation of amines with secondary alcohols via hydrogen autotransfer (HA) strategy is very challenging and has been scarcely reported, even under precious metal catalysis. Herein, an efficient N-alkylation of amines, including benzylamines using secondary alcohols as alkylating agents, is reported. This reaction is catalyzed by a molecularly defined NNN-Ni(II) pincer complex, and the reaction operates under mild, benign conditions. Various substrates and functional groups were tolerated. Preliminary mechanistic studies suggest that the N-alkylation reaction proceeds via a hydrogen autotransfer mechanism.

Ni-Catalyzed α-Alkylation of Unactivated Amides and Esters with Alcohols by Hydrogen Auto-Transfer Strategy.

A transition-metal-catalyzed borrowing hydrogen/hydrogen auto-transfer strategy allows the utilization of feedstock alcohols as an alkylating partner, which avoids the formation of stoichiometric salt waste and enables a direct and benign approach for the construction of C-N and C-C bonds. In this study, a nickel-catalyzed α-alkylation of unactivated amides and ester (tert-butyl acetate) is carried out by using primary alcohols under mild conditions. This C-C bond-forming reaction is catalyzed by a new, molecularly defined nickel(II) NNN-pincer complex (0.1-1 mol %) and proceeds through hydrogen auto-transfer, thereby releasing water as the sole byproduct. In addition, N-alkylation of cyclic amides under Ni-catalytic conditions is demonstrated.

Cobalt-catalyzed acceptorless dehydrogenative coupling of aminoalcohols with alcohols: direct access to pyrrole, pyridine and pyrazine derivatives.

Here, the first example is reported of a new, molecularly defined SNS-cobalt(ii) catalyst for the acceptorless dehydrogenative coupling (ADC) of unprotected amino alcohols with secondary alcohols leading to pyrrole and pyridine derivatives.

Metal-free radical trifluoromethylation of ß-nitroalkenes through visible-light photoredox catalysis.

A catalytic method for functional group interconversion is immensely important in modern sciences. Here, we report an efficient catalytic conversion of nitroalkenes to highly stereoselective 1-trifluoromethylalkenes at room temperature. This unprecedented metal-free photocatalytic strategy is simple and operates under visible-light irradiation using the commercially available CF3 source.

Predesigned Metal-Anchored Building Block for In Situ Generation of Pd Nanoparticles in Porous Covalent Organic Framework: Application in Heterogeneous Tandem Catalysis.

The development of nanoparticle-polymer-hybrid-based heterogeneous catalysts with high reactivity and good recyclability is highly desired for their applications in the chemical and pharmaceutical industries. Herein, we have developed a novel synthetic strategy by choosing a predesigned metal-anchored building block for in situ generation of metal (Pd) nanoparticles in the stable, porous, and crystalline covalent organic framework (COF), without using conventional reducing agents. In situ generation of Pd nanoparticles in the COF skeleton is explicitly confirmed from PXRD, XPS, TEM images, and 15N NMR spectral analysis. This hybrid material is found to be an excellent reusable heterogeneous catalyst for the synthesis of biologically and pharmaceutically important 2-substituted benzofurans from 2-bromophenols and terminal alkynes via a tandem process with the turnover number up to 1101. The heterogeneity of the catalytic process is unambiguously verified by a mercury poisoning experiment and leaching test. This hybrid material shows superior catalytic performance compared to commercially available homogeneous as well as heterogeneous Pd catalysts.

Expedient Cobalt-Catalyzed C-H Alkynylation of (Enantiopure) Benzylamines.

A unified strategy for cobalt-catalyzed ortho-C-H bond alkynylation of benzylamines is reported. Simple, commercially available CoBr2 was used as a cobalt source. The developed alkynylation strategy is robust and efficient and has a broad substrate scope including 1°, 2°, and 3° benzylamines. The mechanistic study shows that C-H bond cleavage is reversible, and the kinetic study illustrates that the rate of reaction depends solely on the catalyst.

Reversed reactivity of anilines with alkynes in the rhodium-catalysed C-H activation/carbonylation tandem.

Development of multicatalytic approach consisting of two or more mechanistically distinct catalytic steps using a single-site catalyst for rapid and straightforward access of structurally complex molecules under eco-benign conditions has significance in contemporary science. We have developed herein a rhodium-catalysed C-H activation strategy which uses an unprotected anilines and an electron-deficient alkynes to C-C bonded products as a potential intermediate in contrast to the archetypical C-N bonded products with high levels of regioselectivity. This is followed by carbonylation of C-H bond activated intermediate and subsequent annulation into quinolines has been described. This rhodium-catalysed auto-tandem reaction operates under mild, environmentally benign conditions using water as the solvent and CO surrogates as the carbonyl source with the concomitant generation of hydrogen gas. The strategy may facilitate the development of new synthetic protocols for the efficient and sustainable production of chemicals in an atom-economic way from simple, abundant starting materials.

Well-defined palladium(ii) complexes for ligand-enabled C(sp(3))-alkynylation.

The first example of ligand-enabled C(sp(3))-alkynylation of 8-methylquinoline is reported. The reaction is catalysed by well-defined Pd(ii) complexes. The present C(sp(3))-alkynylation has a broad substrate scope as well as functional group tolerance and proceeds efficiently under mild conditions.