Efficient Synthesis of 5‐Chalcogenyl‐1,3‐oxazin‐2‐ones by Chalcogen‐Mediated Yne–Carbamate Cyclisation: An Experimental and Theoretical Study

Abstract

A very efficient synthesis of 5‐chalcogenyl‐1,3‐oxazin‐2‐ones has been accomplished by the chalcogen‐mediated yne–carbamate cyclisation of chiral, non‐racemic N‐Cbz‐protected propargylic amines using PhXY (X = Se, S, Te; Y = Br or Cl) as electrophile sources. The reactions gave good‐to‐excellent yields for a wide range of substrates. In all cases the reaction was totally regioselective, occurring by a 6‐endo‐dig process regardless of the nature of the reagent and of the substituents in the starting material. This methodology permits the formation of the 1,3‐oxazin‐2‐one moiety as well as the simultaneous installation of a chalcogen functionality onto the heterocyclic ring. The experimental results have been rationalised by theoretical studies at the B3LYP/6‐311G* level of theory.

In Situ Formation of RSCl/ArSeCl and Their Application to the Synthesis of 4-Chalcogenylisocumarins/Pyrones from o-(1-Alkynyl)benzoates and (Z)-2-Alken-4-ynoates

“…Isocoumarins − and pyrones, , the core structures of many naturally occurring compounds, have been found to display a broad spectrum of biological activities including antimicrobial, − androgen-like, phytotoxic, antifungal, , and pheromonal effects. On the other hand, the past decade has witnessed a growing interest in organochalcogenide compounds, since the installation of chalcogen functional groups into organic molecules can significantly improve their physical and chemical features as well as enhance their biological activities. − …”

Transition Metal‐Free Synthesis of Carbo‐ and Heterocycles via Reaction of Alkynes with Organylchalcogenides

“…The electrophilic cyclization of quiral acyclic alkynes containing N-Cbz-protected amines to produce 5-chalcogenyl-1,3oxazin-2-ones 22 was proposed by Domingo, Pedro, and co-workers (Scheme 11). [38] In this study, various N-Cbz-protected propargylic amines containing both electron-withdrawing and electron-donating substituents are readily cyclized by a 6-endo-dig mode. The reactivity of different phenylchalcogenyl halides as the electrophilic source in the electrophilic cyclization reaction was evaluated, which reacted in the following order: PhSeCl > PhSCl > PhTeBr.…”

Recent Advances in the Synthesis of 3,4-Dihydropyran-2-Ones Organocatalyzed by N-Heterocyclic Carbenes

“…Finally, in 2022 Tiwari and co-workers successfully developed the first enantioselective method for synthesizing selenylated dihydropyranones. This type of molecule is of particular interest due to the well-known augmentation of physical, chemical, and biological properties through the functionalization of organic molecules with selenyl groups [77][78][79]. By using NHC organocatalysis, the authors achieved high yields and excellent enantioselectivities of chiral selenylated dihydropyranones 40 from α, β-unsaturated aldehydes 1 and selenyl vinyl ketones 39 (Scheme 19) [80].…”