Siba P. Midya

Transition-metal-catalyzed hydrogen-transfer annulations: access to heterocyclic scaffolds.

The ability of hydrogen-transfer transition-metal catalysts, which enable increasingly rapid access to important structural scaffolds from simple starting materials, has led to a plethora of research efforts on the construction of heterocyclic scaffolds. Transition-metal-catalyzed hydrogen-transfer annulations are environmentally benign and highly atom-economical as they release of water and hydrogen as by-product and utilize renewable feedstock alcohols as starting materials. Recent advances in this field with respect to the annulations of alcohols with various nucleophilic partners, thus leading to the formation of heterocyclic scaffolds, are highlighted herein.

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.

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.

Nickel-catalyzed direct alkynylation of C(sp2)–H bonds of amides: an “inverse Sonogashira strategy” to ortho-alkynylbenzoic acids

Nickel-catalyzed direct alkynylation of C(sp2)–H bonds of amides using commercially available, inexpensive 8-aminoquinoline as a removable bidentate directing group is described. The present ortho-alkynylation has a broad substrate scope, functional group tolerance and high regiocontrol, and can be scaled up. The efficiency and selectivity of this strategy provide sustainable routes to a diverse array of ortho-alkynylbenzoic acids under Ni(II)-catalyzed conditions.

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.

Phosphine-free cobalt pincer complex catalyzed Z-selective semi-hydrogenation of unbiased alkynes

Herein, we report a novel, molecularly defined NNN-type cobalt pincer complex catalyzed transfer semi-hydrogenation of unbiased alkynes to Z-selective alkenes. This unified process is highly stereo- and chemo-selective and exhibits a broad scope as well as wide functional group tolerance. Ammonia-borane (AB), a bench-stable substrate with high gravimetric hydrogen capacity, was used as a safe and practical transfer hydrogenating source.

Molecular Complexes for Effective Inhibition of Tau Aggregation

Tau is an axonal protein known to form abnormal aggregates and is the biomarker of Alzheimer’s disease. Metal-based therapeutics for inhibition of Tau aggregation is limited and rarely reported in the contemporary science. Here, the first example is reported of a rationally designed molecular cobalt(II)-complexes for effective inhibition of Tau and disaggregation of preformed Tau fibrils. The mechanistic studies revealed that the prevention of Tau aggregation by CBMCs is concentration-dependent and Tau seldom exhibits conformational changes. Interestingly, CBMCs play a dual role by causing disassembly of preformed aggregates as well as complete Tau inhibition. We believe that this unprecedented finding by the newly developed molecular complexes has a potential to lead to developing innovative metal-based therapeutics for Alzheimer’s disease.

Ni-catalyzed α-alkylation of unactivated amides and esters with alcohols via 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.

Direct access to N-alkylated amines and imines via acceptorless dehydrogenative coupling catalyzed by a cobalt(II)-NNN pincer complex

A simple, phosphine-free Co(II)-NNN pincer complex catalyzed direct N-alkylation of anilines with alcohols via hydrogen auto-transfer (HA) and selective acceptorless dehydrogenative coupling (ADC) of benzylamines with alcohols affording imines with the liberation of molecular hydrogen and water is reported.