A Route to Triazole-Fused Sultams via Metal-Free Base-Mediated Cyclization of Sulfonamide-Tethered 5-Iodotriazoles

Abstract

An efficient direct approach to triazole-fused sultams has been developed. The key step of the proposed strategy is base-mediated cyclization of sulfonamide-tethered 5-iodo-1,2,3-triazoles which are readily available via an improved protocol for Cu-catalyzed 1,3-dipolar cycloaddition. The annulation of the sultam fragment to the triazole ring proceeds smoothly under transition-metal-free conditions in the presence of Cs2CO3 in dioxane at 100 °C and affords fused heterocycles in high yields up to 99%. The favorability of an SNAr-like mechanism for the cyclization was supported by DFT calculations. The applicability of the developed procedure to modification of natural compounds was demonstrated by preparation of a deoxycholic acid derivative.

Facile Access to Triazole-Fused 3,1-Benzoxazines Enabled by Metal-Free Base-Promoted Intramolecular C–O Coupling

“…23 Considering the favorability of intramolecular transformations, we supposed that the use of nucleophile-tethered 5-iodotriazoles could significantly facilitate the substitution reaction. This hypothesis was perfectly confirmed by the cyclization of 5-iodotriazoles bearing sulfonamide 24 and phenol 25 moieties. Herein, we report an expansion of this strategy towards the development of an alternative efficient approach to valuable triazole-fused 3,1benzoxazines (Scheme 1).…”

“…In a prior report, we showed that addition of a catalytic amount of Cu powder could be beneficial for the CuIAAC reaction. 24 Indeed, this modification (method B) enhanced the yield of 1a from 65 to 92% in comparison with the standard protocol (method A). Therefore, method B and related method C, employing a double loading of the catalyst, were considered more reliable and were used for the preparation of other iodotriazoles 1.…”

Progress in the Synthesis of Fused 1,2,3‐Triazoles

“…Recently, Latyshev's group developed the new synthesis of triazole fused sultams 355 via base mediated cyclization of sulfonamide derived 5‐iodo‐1,2,3‐triazoles 354 (Scheme 112). [112] DFT calculations suggest that the cyclization event occurred by S N Ar‐like mechanism. They found that the electronic nature of substituents at triazole ring and at nitrogen of sulfonamide did not affect the yield.…”

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

“…A good to excellent yield of sultam derivatives 104 containing aryl and alkyl substituents on the triazole ring was achieved under optimized conditions. The reaction displayed extensive diversity and excellent functional group tolerance It should be noted once again that Cu-catalyzed triazoles were obtained in good to excellent yield by using 10% CuI and 10% Cu, which were subsequently converted to fused sultams ( Scheme 30 ) [ 56 ].…”