C-H Arylation of Nitroimidazoles and Nitropyrazoles Guided by the Electronic Effect of the Nitro Group

Abstract

A palladium-catalyzed C-H arylation reaction of nitroimidazoles and nitropyrazoles was developed using aryl bromides as arene donors. The electron-withdrawing effect of the nitro group allows for direct C-H arylation reactions of the nitro diazoles with high regioselectivity under mild conditions. The new C-H arylation approach is thus complementary to nucleophilic substitution reactions, enabling the preparation of complex nitroazole compounds.

Palladium Catalyzed Arylation and Benzylation of Nitroarenes Using Aryl Sulfonates and Benzyl Acetates

“…Substrate 1 has two distinct C–H bonds (H a and H b ) that can undergo arylation. Consistent with previous reports on arylation using aryl halides 4 product 1a is derived via the preferential arylation of the more acidic C–H a bond. 15 Unlike arylations using aryl bromides, 4 transformations using aryl tosylates do not require copper(I) additives.…”

“…In contrast to the analogous reaction with halide electrophiles 4 the use of PPh 3 does not lead to 1a . Additionally, the bidentate dcype ligand, which is effective for arylations of arenes using tosylates and mesylates 12a,c does not promote the arylation of nitropyrazole (entry 6).…”

“…K 2 CO 3 was obtained from JT Baker and used as received. The azoles, 4 tosylates, 12a mesylates 12c and benzyl acetates were prepared using literature procedures. Anhydrous xylene was obtained from Aldrich and used as received.…”

“…2 Reduction of the nitro group serves as a versatile handle for structural elaboration through cross-coupling and functional group transformation of the resulting amino group. 3 In lieu of these applications of nitroarenes, a few reports have detailed the arylation of nitroazoles (Schemes 1a, and 2a) 4 and nitrobenzene derivatives (Scheme 4a) 2, 5 using halide electrophiles. 6, 7, 8 The allylation and benzylation of nitroazoles using allyl acetate and benzyl chloride, respectively has also been realized (Scheme 3a).…”

“…Notably, functionalized pyrazoles, imidazoles and nitrobenzene derivatives find applications in the synthesis of pharmaceuticals, agrochemicals, or ligands for transition metals. 1, 9, 4c …”