Novel Organosulfur Building Blocks for Heterocycle Synthesis

Dedicated to Professor Brindaban Chandra Ranu on the occasion of his 75th birthday.

Abstract

The present article provides a personalized account of our recent work on the synthesis of substituted and fused five-membered heterocycles using various organosulfur building blocks, derived primarily through base-mediated condensation of active methylene compounds with (het)aryl/alkyl dithioesters, which have not been previously explored. We initially describe the ring-opening transformations of 4-[(methylthio)-(het)aryl-methylene]-2-phenyl-5-oxazolones, leading to the synthesis of functionalized oxazoles, thiazoles, and bisoxazoles. We then go on to focus on the synthesis of substituted benzothiophenes, indoles, and benzofurans, as well as their hetero-fused analogs. These compounds are synthesized via transition-metal-catalyzed intramolecular C–heteroatom (C–S, C–N, C–O) bond formation (via cross-coupling or C–H bond functionalization) of various reactive organosulfur intermediates, derived from base-mediated condensation of 2-bromo(het)arylacetonitriles, acetates, or desoxybenzoins or the corresponding 2-unsubstituted precursors. Finally, we highlight the synthetic applications of a new class of previously unexplored organosulfur building blocks, namely, unsymmetrically substituted 1,3-bis(het)aryl-1,3-monothioketones, derived via base-mediated condensation of ketones with (het)aryl/alkyl dithioesters, for the regioselective synthesis of substituted pyrazoles, isoxazoles, thiophenes, imidazoles, and benzothiophenes.

1 Introduction

2 4-[(Methylthio)-het(aryl)-methylene]-2-phenyl/2-(2-thienyl)-5-oxazolones: Versatile Templates for the Synthesis of Oxazoles, Thiazoles, and Bisoxazoles

3 Synthesis of Benzothiophenes, Indoles, and Benzofurans via Transition-Metal-Catalyzed Intramolecular C–Heteroatom Bond Formation

4 1,3-Bis(het)arylmonothio-1,3-diketones and 1,3-Bis(Het)aryl-3-(methylthio)-2-propenones: Versatile Intermediates for the Regioselective Synthesis of Five-Membered Heterocycles

5 Conclusion

Key words

organosulfur building blocks - (het)aryl/alkyl dithioesters - 4-[(methylthio)-het(aryl)-methylene]-2-phenyl-5-oxazolones - transition metal catalyzed intramolecular C-heteroatom bond formation - 1,3-bis(het)aryl-1,3-monothioketones

Publication History

Received: 15 August 2024

Accepted: 10 September 2024

Accepted Manuscript online:
10 September 2024

Article published online:
09 October 2024

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