Synthesis Of Indolizine Derivatives Via Pd(0)–Catalyzed Oxidative Annulation Of Aroyl Chlorides

Indolizine is one of the most important skeletons among nitrogen-containing heterocycles and has been found in biologically active compounds.In this regard,transformation utilizing readily available substrates to access diverse indolizines,especially those bearing an electron-withdrawing group at the C-2 position,are meaningful exploration.Among the strategies to synthesize indolizine structures,Pd-catalyzed cascade carbonylative cyclization of propargylic pyridines is an efficient method for the synthesis of indolizines.Introduction of a carbonyl functional group at the C-2 position of indolizines was achieved by using carbon monoxide.But the use of toxic carbon monoxide restricted its application,we try to find an alternative to achieve this transformation more safely and conveniently.Considering the convenient formation of acylpalladium species from acid chlorides and Pd（0）complex,acid chlorides is a good electrophilic partner in Pd-catalyzed coupling reactions..An efficient synthesis of indolizines through Pd-catalyzed cyclization of propargylic pyridines with acid chlorides has been studied.The reactions proceeded smoothly in the presence of 2 mol%Pd（PPh₃）₄,THF as the solvent and Et₃N as the base,affording a variety of indolizine derivatives in high yield at 60℃.In the process,the cyclization was triggered by the in situ formed Ar COPd X species obtained from the facile oxidative addition of aroyl chloride to Pd（0）complex.In conclusion,an enfficient synthesis of indolizins from cheap and readily available starting materials under mild conditions has been developed,which has potential application in the synthesis of drug intermediates and functional matterials.