Hypervalent iodine mediated Pd(II)‐catalyzed ortho‐C(sp²−H) functionalization of azoles deciphering Hantzsch ester and malononitrile as the functional group surrogates

Abstract

CÀ H bond activation has surfaced as a transformative toolbox for the efficient assembly of biologically important molecules. However, despite of major advances in palladium, rhodium and silver catalysis, yet palladium(II)-catalyzed, iodobenzene diacetate (PIDA) mediated CÀ H bond activation in azole skeleton has deluged with interesting wining outcome. Concentrating on that we herein report on the involvement of 4-functionalized 1,4-dihydropyridines (R-DHPs) as the representative surrogates of benzoyl, pivalyl and ethoxycarbonyl groups and in presence of PIDA it releases appropriate functional radical (following single electron transfer oxidation of R-DHPs under thermal condition)to become the part of ortho-functionalized azoles via Pd(II) catalysis. In case of cyanation reaction, malononitrile has served the key source of nitrile functionality by undergoing oxidative CÀ CN bond cleavage in presence of PIDA and with the help of Pd(II) catalyst it offers ortho-cyanated azoles. Additionally, the selective formation of C-3 benzoyl and ester functionalized indazole derivatives in absence of Pd(II)catalyst and the unprecedented formation of homo-coupling products between two identical 2H-indazoles are also notable outcome of present strategic access. Overall this protocol operates under mild condition, tolerates a wide range of structural moieties and gives versatile azole derivatives in high efficiency. The antioxidant properties of the synthesized 2thiophenyl benzoyl selenazole and isoselenazole are further evaluated using a chemically defined method. The Copperascorbate (CuÀ As) was utilized as an oxidative stress generator. Out of screened azoles, the 2-benzoyl isoselenazole compound (3 i) displays magnificent antioxidant property as compared to the 2-thiophenyl benzoyl selenazole (3 g).

Ru(ii) catalyzed chelation assisted C(sp2)–H bond functionalization along with concomitant (4 + 2) annulation

“…To fulfil the aim of developing a powerful and straightforward synthetic route for the swift and effective construction of diversely functionalized coumarin-fused pyridone molecules, we have focused on a transition-metal-mediated chelation-assisted route, since the past decade has seen the burgeoning of directing-group-assisted metal-mediated C–H functionalization due to its handiness and domino character. 6 Moreover, it features the direct transformation of a proximal C–H bond to C–C and C–heteroatom bonds, inducing the respective directing groups explicitly in a regioselective manner so that the directing group becomes the source of the heteroatom or fragment of the envisioned heterocycle. Concentrating on literature reports based on C–H activation mediated research findings on coumarin derivatives using transition metals, it was revealed that Das et al 7 (Scheme 1a) had reported an efficient two-step protocol to prepare Π-extended N-heterocycles involving Rh( iii )-catalyzed C–H activation starting from 3-acetamidocoumarins and alkynes, where the acetyl group acted as a traceless directing group to prepare pyrrolo coumarin moieties.…”