Murarka, Sandip

We present an organophotoredox-catalyzed direct Csp3-H alkylation of 3,4-dihydroquinoxalin-2-ones employing N-(acyloxy)pthalimides to provide corresponding products in good yields. A broad spectrum of NHPI esters (1°, 2°, 3°, and sterically encumbered) participates in the photoinduced alkylation of a variety of 3,4-dihydroquinoxalin-2-ones. In general, mild conditions, broad scope with good functional group tolerance, and scalability are the salient features of this direct alkylation process.

We disclose N′-arylidene-N-acryloyltosylhydrazides as novel skeletons for the synthesis of biologically relevant alkylated pyrazolones through a photoinduced radical cascade with N-(acyloxy)pthalimides as readily available alkyl surrogates. The reaction proceeds through the formation of a photoactivated electron donor-acceptor (EDA) complex between alkyl N-(acyloxy)phthalimide (NHPI) esters and LiI/PPh3 as a commercially available donor system. The reaction exhibits a broad scope and scalability, thereby enabling synthesis of a broad spectrum of functionally orchestrated alkylated pyrazolones under mild and transition-metal-free conditions.

We present an electrochemical alkylation of azauracils using N-(acyloxy)phthalimides (NHPI esters) as readily available alkyl radical progenitors under metal- and additive-free conditions. Several azauracils are shown to undergo alkylation with an array of NHPI esters (1°, 2°, 3°, and sterically congested), providing the desired products in good to excellent yields. This operationally simple method is robust, scalable, and suitable for both batch and flow setups.

A visible light-induced green and sustainable N−H functionalization of (aza)uracils with α-diazo esters leading to imide alkylation is described. The reaction does not require any catalyst or additive and proceeds under mild conditions. Moreover, an intriguing three component coupling was observed when (aza)uracils were allowed to react with α-diazo esters in cyclic ethers (e. g. 1,4-dioxane, THF) as a solvent. Both the insertion and three-component coupling features broad scope with good to excellent yields and appreciable functional group tolerance. Notably, the divergent method enables modification of natural products and pharmaceuticals, thereby facilitates access to potentially biologically active compounds.

Quaternary carbons are embedded in various natural products, pharmaceuticals, and organic materials. However, constructing this valuable motif is far from trivial. Conventional approaches mainly rely on classical polar disconnections and encounter bottlenecks concerning harsh conditions, functional group tolerance, regioselectivity, and step economy. In this context, Kawamata, Baran, Shenvi, and co-workers recently demonstrated that two feedstock chemicals, alkyl carboxylic acids and olefins, could be utilized to construct tetrasubstituted carbons in the presence of an inexpensive iron porphyrin catalyst and a suitable reductant combination through quaternization of the radical intermediates. The method enables access to various sterically encumbered quaternary carbons under mild and robust conditions. Taking a complete detour from conventional approaches, the present heteroselective radical–radical coupling simplifies the synthesis of quaternary carbon-containing molecules through an innovative and distinctive disconnection approach.

In recent times, diaryliodonium reagents (DAIRs) have witnessed a resurgence as arylating reagents, especially under photoinduced conditions. However, reactions proceeding through electron donor-acceptor (EDA) complex formation with DAIRs are restricted to electron-rich reacting partners serving as donors due to the well-known cage effect. We discovered a practical and high-yielding visible-light-induced EDA platform to generate aryl radicals from the corresponding DAIRs and use them to synthesize key chalcogenides. In this process, an array of DAIRs and dichalcogenides react in the presence of 1,4 diazabicyclo[2.2.2]octane (DABCO) as a cheap and readily available donor, furnishing a variety of di(hetero)aryl and aryl/alkyl chalcogenides in good yields. The method is scalable, features a broad scope with good yields, and operates under open-to-air conditions. The photoinduced chalcogenation technology is suitable for late-stage functionalizations and disulfide bioconjugations and facilitates access to biologically relevant thioesters, dithiocarbamates, sulfoximines, and sulfones. Moreover, the method applies to synthesizing diverse pharmaceuticals, such as vortioxetine, promazine, mequitazine, and dapsone, under amenable conditions.

We report here a practical and cost-effective method for the synthesis of CHF2-containing benzimidazo- and indolo[2,1,a]-isoquinolin-6(5H)-ones through a visible light-mediated difluoromethylation/cyclization cascade. The method, which affords functionalized multifused N-heterocyclic scaffolds in moderate to high yields under mild reaction conditions, is also easily scalable using low-cost 3D printed photoflow reactors.

There is a scarcity of general strategies for the site-selective α-Csp3-H arylation of glycine derivatives to synthesize nonproteinogenic α-arylglycines that occur frequently in commercial drugs and bioactive molecules. We disclose a copper-photoredox-catalyzed site-selective α-Csp3-H arylation of glycine derivatives using diaryliodonium reagents (DAIRs) as arylating agents. This strategy harnesses the underexplored ability of DAIRs to serve as arylating agents under visible-light irradiation using copper salts as photocatalysts. The method applies to the glycine-selective C-H arylation of peptides with electronically and structurally diverse DAIRs. Moreover, we demonstrate that the photoinduced copper-catalyzed single electron transfer (SET) strategy can be coupled with the halogen atom transfer (XAT) process in the presence of alkyl iodides to accomplish site-selective α-Csp3-H alkylation of glycines and peptides. In this synergistic SET/XAT approach, phenyl radicals generated from diphenyl iodonium triflate mediate the XAT process to generate alkyl radicals from alkyl iodides. Both of these methods operate under mild conditions and exhibit broad scope with appreciable functional group tolerance. Overall, the divergent toolbox strategies presented here facilitate access to various alkylated and arylated glycines and peptides and enable bioconjugation between peptides and drug molecules.

We disclose a photoredox-catalyzed arylative radical cascade between N′-arylidene-N-acryloylhydrazides and diaryliodonium reagents to obtain the corresponding benzylated pyrazolones in good yields. The protocol was extended to three-component coupling involving the 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) adduct as a sulfur dioxide surrogate for the synthesis of arylsulfonylated pyrazolones. Both reactions exhibit broad scope, scalability, and high functional group tolerance.

Guided by the principle of biology-oriented synthesis, a collection of compounds with decahydro-4,8-epoxyazulene scaffold occurring in bioactive natural products was synthesized by the rhodium(II)-catalyzed 1,3-dipolar cycloaddition reaction of pentafulvenes and carbonyl ylides. The products can be obtained in moderate to high yields, with moderate enantioselectivity and excellent diastereoselectivity and regioselectivity.