Metal‐Free Multicomponent Reaction for Synthesis of 4,5‐Disubstituted 1,2,3‐(NH)‐Triazoles

Abstract

A metal-free domino reaction was developed for efficient synthesis of 4,5-disubstituted 1,2,3-(NH)-triazoles by sequentially coupling sulfur salts with aldehydes and sodium azide. In the presence of L-proline, olefinic sulfur salt intermediates rather than epoxides are formed in situ via the coupling of sulfur salts with aldehydes and cyclize with azide ion. This process features mild conditions, high efficiency, commercially available starting materials, and wide substrate scope.

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

“…Recently, Wu and co-workers used acceptor-substituted vinylsulfonium salts in a formal (3 + 2)-cycloaddition with sodium azide (Scheme 89a). 321 Interestingly, the vinylsulfonium salt could be generated in situ by nucleophilic substitution followed by aldol condensation with an aldehyde using catalytic L-proline. These acceptor-substituted vinylsulfonium species then engage the azide anion, leading to a range of triazoles (540).…”

Recent Progress in Catalytic Synthesis of 1,2,3-Triazoles

“…Other small organic molecules, such as morpholine (91%), piperidine (93%), and other aminoacids, were tested in the same reaction conditions, but the best results were obtained using DMSO as a solvent at room temperature (Scheme 58). This procedure has been demonstrated high tolerance not only toward aldehyde substrates but also toward some organohalides, obtaining in all cases excellent results [113]. In recent years, the cycloaddition reaction of nitroalkenes was largely explored for the synthesis of NH-1,2,3-triazoles, using different catalytic conditions [114,115].…”

A Mild Multi-Component Reaction for the Synthesis of 4,5-Disubstituted 1H-1,2,3-Triazoles from Phosphonium Salts, Aldehydes, and Sodium Azide

“…Olefinic sulfur salt intermediates are formed via the coupling of sulfur salts with aldehydes in the presence of L-proline. 7 Thus, our initial experiment was performed with (ethoxycarbonylmethyl)triphenylphosphonium bromide (1a), benzaldehyde (2a), and NaN 3 catalyzed by L-proline. The mixture was stirred in DMSO solution at room temperature for 24 hours and the expected product, triazole 3a, was obtained in a 75% isolated yield.…”