Study On ?-C(sp~3)-H Functionalization Of Nitrones

Imines with valuable containing C=N bonds,also called Schiff bases,play privileged role as structural motifs of many bioactive materials and synthetic origins.Different strategies are available for the construction of such structural motifs,yet direct ?-C(sp3)-H bond functionalization of proper amines has drawn unwavering attentions,including cross dehydrogenation coupling and redox-neutral strategies.Herein,we reported a novel method to synthesize ?,?-unsaturated imines by?-C(sp3)-H functionalization of nitrones.The reaction conditions in terms of Lewis acids,Lewis bases,temperature and solvents were screened and optimized.The limit and scope of carbonyl substrates was examined,and a mechanistic proposal was presented and discussed.(1)A novel approach of ?-C(sp3)-H alkenylation of cyclic nitrones catalyzed by strong Lewis acid In(OTf)3 in the presence of Lewis base PR3(R = Et or NMe2)with aldehydes to ?,?-unsaturated imines was developed.It provides a choice to obtain?,?-unsaturated imines with a yield of 85%,when both of the loading of nitrone(3.0 equiv.)and the temperature(120 ?)were relatively high.(2)An alternative method of ?-C(sp3)-H alkenylation of cyclic nitrones catalyzed by weak Lewis acid SiCl4 was developed.The optimized yield of 92%was obtained from the reaction of aldehyde and nitrone(2.0 equiv.)at 60 ?.In addition,in the case of 6-membered nitrone,a[1,3]-hydride shift within the resulted ?,?-unsaturated imines renders the aromatization leading to 3,5-dialkylpyridines.The catalytic transformation features broad substrate scope and good functional tolerance.(3)Mechanistic studies show that:the synthesis of ?,?-unsaturated imines mainly involves deoxygenation and aldol condensation,each proceeding under a cooperation effect between Lewis acid and Lewis base.Besides,both the acidity and hydrolytic stability of the weak SiCl4U were supposed to be enhanced by coordination with phosphine oxide(R = Et)or phosphoric triamide(R = NMe2).Therefore,an efficient Lewis base activated Lewis acid system of SiCl4-catalyzed/PR3-mediated was constructed to achieve a mild transformation of nitrones to ?,?-unsaturated imine via?-C(sp3)-H functionalization with aldehydes/ketones.