Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

Abstract

A series of new phosphonocarboxylates containing an imidazo[1,2-a]pyridine ring has been synthesized via the microwave-assisted Mizoroki–Heck reaction. The efficient modification of the imidazo[1,2-a]pyridine ring has been achieved as late-stage functionalization, enabling and accelerating the generation of a library of compounds from a common precursor.

Synthesis and site selective C–H functionalization of imidazo-[1,2-a]pyridines

“…Functionalizations of imidazo-pyridines have been reported by several groups, but pre-functionalization was required, such as C6 functionalization of imidazopyridines performed by the Buchwald group. 141–143…”

“…Functionalizations of imidazo-pyridines have been reported by several groups, but prefunctionalization was required, such as C6 functionalization of imidazopyridines performed by the Buchwald group. [141][142][143] 3.6 C8 functionalization Recently, our group, for the very first time, demonstrated a regioselective C8 alkenylation of imidazo[1,2-a]pyridines through nitrogen chelation. The reaction was performed by treating imidazopyridines 181 with alkene partner 182 in the presence of a palladium catalyst, with silver carbonate as a base, in toluene at 120 °C to obtain the targeted product 183.…”

Data_Sheet_1.PDF

“…In order to obtain compounds 1k and 1l, equipped with an alkyl chain, the Mizoroki-Heck reaction was applied (Scheme 4), using Pd(OAc) 2 and DIPEA and microwave irradiation (Kusy et al, 2020). As we have previously shown, such functionalization with appropriate olefin can be carried out for both types of compounds 5a/5m and 6a/6m.…”