Murarka, Sandip

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.

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.

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.

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.

Recent years have witnessed a significant advancement in the field of radical oxidative coupling of ketones towards the synthesis of highly useful synthetic building blocks, such as 1,4-dicarbonyl compounds, and biologically important heterocyclic and carbocyclic compounds. Besides oxidative homo- and cross-coupling of enolates, other powerful methods involving direct C(sp 3)-H functionalizations of ketones have emerged towards the synthesis of 1,4-dicarbonyl compounds. Moreover, direct α-C-H functionalization of ketones has also allowed an efficient access to carbocycles and heterocycles. This review summarizes all these developments made since 2008 in the field of metal-catalyzed/promoted radical-mediated functionalization of ketones at the α-position. 1 Introduction 2 Synthesis of 1,4-Dicarbonyl Compounds 3 Synthesis of Heterocyclic Scaffolds 4 Synthesis of Carbocyclic Scaffolds 5 Conclusion.

Recent years have witnessed a resurgence of novel, efficient and practical protocols for radical-mediated cross-coupling reactions involving N-(acyloxy)phthalimides (NHPI esters) as redox-active esters. After the initial discovery of the redox-active properties of NHPI esters, exciting examples of SET-based cross-coupling reactions under thermal or photolytic conditions leading to diverse C–X (X=C, B, Si, Se, S) bonds have been published. The operational simplicity and broad applicability exhibited in redox-active NHPI ester-based cross-couplings bode well for their widespread adoption. The review presented herein covers all the recent developments in the field of redox-active ester (RAE)-based cross-couplings since the initial discovery. Depending on the conditions employed the reactions have been categorized into photoinduced and non-photoinduced cross-couplings with representative examples and insightful mechanistic discussions. (Figure presented.).

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.

Methods enabling direct C−H alkylation of heterocycles are of fundamental importance in the late-stage modification of natural products, bioactive molecules, and medicinally relevant compounds. However, there is a scarcity of a general strategy for the direct C−H alkylation of a variety of heterocycles using commercially available alkyl surrogates. We report an operationally simple palladium-catalyzed direct C−H alkylation of heterocycles using alkyl halides under the visible light irradiation with good scalability and functional group tolerance. Our studies suggest that the photoinduced alkylation proceeds through a cascade of events comprising, site-selective alkyl radical addition, base-assisted deprotonation, and oxidation. A combination of experiments and computations was employed for the generalization of this strategy, which was successfully translated towards the modification of natural products and pharmaceuticals. © 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.