5-(Methylthio)tetrazoles as versatile synthons in the stereoselective synthesis of polycyclic pyrazolines via photoinduced intramolecular nitrile imine–alkene 1,3-dipolar cycloaddition

Abstract

A key thioether substituent in readily accessible 2-alkyl-5-(methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other functionalities. This synthetic platform has been applied to the concise total syntheses of the alkaloid natural products (±)-newbouldine and withasomnine.

Conversion of Arylboronic Acids to Tetrazoles Catalyzed by ONO Pincer-Type Palladium Complex

“…Chemistry of nitrogen-rich heterocycles gains immense importance due to their diverse application . Specifically, tetrazoles are an ubiquitous structural motif very often utilized in pharmaceuticals (Figure ), as ligands in coordination chemistry, in organocatalysis, as synthons in organic synthesis as well as in various materials science applications including polymers, photosensitive agents, energy materials, and specialty explosives . In the literature, a plethora of methods were reported for the synthesis of 5-substituted 1 H -tetrazole derivatives. , Nevertheless, those protocols have some drawbacks such as, (i) high catalyst loading, (ii) expensive reagents, (iii) harsh reaction conditions; water sensitivity and the involvement of dangerous hydrazoic acid, and (iv) prolonged reaction time and elevated temperature. , Hence, development of an efficient, economical and eco-friendly one-pot methodology to construct the titled heterocyclic frame-works with wide substrate scope is a challenging scientific mission.…”

Luminescent Imidazo[1,5‐a]pyridine Scaffold: Synthetic Heterocyclization Strategies‐Overview and Promising Applications

“…Very recently, pyridine‐2‐ylmethanamines and aldehydes have been reacted in mild, practical conditions to obtain dehydro‐cyclization employing CBr 4 for the synthesis of functionalized imidazo[1,5‐ a ]heterocycles [43] . In Scheme 3 impy nuclei were prepared by dipolar [3+2] cycloaddition reactions, well know synthetic strategies widely reported to the facile and stereoselective synthesis of polycyclic nitrogen compounds [44–47] …”

“…[43] In Scheme 3 impy nuclei were prepared by dipolar [3 + 2] cycloaddition reactions, well know synthetic strategies widely reported to the facile and stereoselective synthesis of polycyclic nitrogen compounds. [44][45][46][47] Dr Giorgio Volpi obtained his bachelor's degree from Turin University in 2007.…”

One-Pot Suzuki-Hydrogenolysis Protocol for the Modular Synthesis of 2,5-Diaryltetrazoles

“…The recent resurgence of photochemistry as a unique and powerful method of forging and manipulating C–C bonds has stimulated the development and adaption of numerous synthetic protocols . One such transformation is the photolysis of the 2,5-diaryltetrazole moiety to yield the versatile nitrile imine 1,3-dipole (Scheme a). − Owing to its facile reactivity with a number of functional groups including alkenes , and carboxylic acids, the nitrile imine has recently found widespread application in fields where an orthogonal reactivity profile (click chemistry) is desirable, such as materials chemistry and chemical biology. , …”