Murarka, Sandip

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.

The past decade has witnessed the emergence of N-(acyloxy)phthalimides (NHPI esters) and its derivatives at the forefront of synthetic methods facilitating the construction of diverse molecular frameworks from the readily available carboxylic acid feedstock. The NHPI esters are predisposed to undergo reductive fragmentation via a single electron transfer (SET) process under thermal, photochemical, or electrochemical conditions to generate the corresponding carbon- or nitrogen-centered radicals that participate in a multitude of synthetic transformations to forge carbon-carbon and carbon-heteroatom bonds. The chemistry involving NHPI esters has received broad applicability not only in well-designed cascade annulations but also in medicinal chemistry and natural product synthesis. This comprehensive Review, broadly categorized according to the nature of the bond formation, details the progress made in this field since the initial discovery by providing representative examples with mechanistic details, with an emphasis on challenges and future directions.

We conceptualized a novel disconnection approach for the synthesis of fused tetrahydroquinolines that exploits a visible light-mediated radical (4 + 2) annulation between alkyl N-(acyloxy)phthalimides and N-substituted maleimides in the presence of DIPEA as an additive. The reaction proceeds through the formation of a photoactivated electron donor-acceptor complex between alkyl NHPI esters and DIPEA, and the final tetrahydroquinolines were obtained in a complete regioselective fashion. The methodology features a broad scope and good functional group tolerance and operates under metal- and catalyst-free reaction conditions. Detailed mechanistic investigations including density functional theory studies provide insight into the reaction pathway.

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.

A metal and base-free, operationally simple, and scalable multicomponent approach towards the synthesis of S-diarylmethane dithiocarbamates is reported. A range of structurally and electronically diverse p-quinone methides are shown to react with a variety of amines, and carbon disulfide to furnish corresponding dithiocarbamates in good to excellent yields under mild conditions. Furthermore, p-QMs embedded with aliphatic substituents are well accommodated. Importantly, these readily accessible compounds demonstrated promising anti-proliferative activity in the low micromolar ranges in lung adenocarcinoma cells, reiterating the importance of the developed methodology. (Figure presented.).

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.

An organophotoredox-catalyzed reduction/addition/oxidation cascade of N-protected maleimides and N-(acyloxy)phthalimides is documented. The mild and efficient redox-neutral process involves the hitherto unknown Giese-type addition of aryloxy-alkyl radicals on N-protected maleimides and a successive oxidation allowing an overall Z-alkenylation of the N-substituted pyrrolidine-2,5-dione motif through a formal translocation of the maleimide double bond.

Late stage functionalization (LSF) through direct X-H manipulations (X = C, N) enables synthetic chemists to accelerate the diversification of natural products, agrochemicals and pharmaceuticals allowing rapid access to novel bioactive molecules without resorting to arduous de novo synthesis. LSF does not only allow tapping of the hitherto unexplored chemical space but also renders the synthetic sequence more straightforward, atom economical and cost-effective. In this regard, the recent decade has witnessed the emergence of hypervalent iodine(iii) reagents as a powerful synthetic tool owing to their easy availability, mild reaction conditions, remarkable oxidizing properties and high functional group tolerance. Iodine(iii) reagents have tremendous applications in the regio- and chemo-selective late-stage functionalization of a diverse variety of heterocycles through an exciting range of transformations, such as oxidative amination, cross-dehydrogenative coupling (CDC), fluoroalkylation, azidation, halogenation and oxidation. The present review, classified according to the types of synthetic methods involved, encompasses all these recent developments in the field of transition-metal-free iodine(iii)-catalyzed/mediated direct functionalizations of heterocycles with representative examples and insightful mechanistic discussions.

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.

Hypervalent iodine(III) reagents have profound applications in a range of facile and novel synthetic methodologies primarily due to their remarkable oxidizing property, robust synthetic utility, environmentally benign nature and easy availability. This chapter emphasises mainly on the various transition metal-free reactions of hypervalent iodine(III) reagents for the construction of a diverse range of heterocyclic compounds.