Cp*Rh^III-Catalyzed Sulfonamide-Directed Ortho Arene C–H Carbenoid Functionalization with Pyridotriazoles

Abstract

In this Letter, triazoles as carbene reagents were used for sulfonamide-directed C–H insertion carbenoid functionalization to construct benzylpyridine sulfonamide dual-pharmacophore compounds. This method is simple and efficient and can be used for the late-stage modification of sulfonamide drugs.

Selective Gram-Scale C–H Carbenoid Functionalization of N-Sulfonylarylamides with a Rhodium Catalyst

“…This Rh-catalyzed regioselective C−H carbenoid functionalization has significant solvent dependence. As shown in Table 1, unlike DCE or toluene (a nonpolar solvent), methanol gave complete conversion in 30 that protic methanol, which is a highly polar solvent, increases the reaction rate ( The substrate scope was investigated by performing the reaction with a series of N-sulfonylarylamides at room temperature in the presence of the Rh III /AgOAc/MeOH catalytic system. As shown in Table 2, various N-tosylbenzamides performed well to give the desired C−H activated products, regardless of whether the substituents were electron-donating or electron-withdrawing groups.…”

“…As one of the most effective and common methods for building C–C, C–O, and C–N bonds, C–H carbenoid functionalization has been widely used in constructing natural products and complex biologically active molecules. − Some transition-metal catalysts such as Ir, Ru, Rh, Pd, and Co complexes can efficiently catalyze some heterocycle-directed aryl C–H carbenoid functionalizations because of strong coordination between heterocycles and metal catalysts. However, substrates with X-type directing groups such as amide or sulfonamide − still need heating to overcome the high activation energies of inert C–H bonds. Achieving room-temperature reactions at low catalyst loadings is, therefore, a challenge.…”

The Role of Sulphonamides and N‐Sulphonyl Ketimines/Aldimines as Directing Groups in the Field of C−H Activation

“…Later, the same group [32] studied the carbenoid functionalization using pyridotriazoles ( 29 ) as carbene reagents for sulphonamide‐directed C−H activation. The reaction was well tolerated with [Cp*RhCl 2 ] 2 as compared with Co or Ir catalysts.…”

Recent Advances in Denitrogenative Reactions of Pyridotriazoles

“…Recently, Xu and co-workers reported the use of pyridotriazoles 37 as carbene reagents for a simple and efficient carbenoid C-H insertion at the ortho position of benzenesulfonamides 38 to construct benzylpyridine-sulfonamide compounds 39 (Scheme 10). 15 A variety of N-acylated sulfonamides 38 showed good reactivity, except pivaloyl-and methoxycarbonyl-substituted sulfonamides. In addition to various triazolopyridines, triazolopyrazine (X = N) also gave the corresponding product 39.…”