A practical photoinitiated synthetic method for the site-selectiveγ-andα-chlorination of C(sp^(3))-H bonds of ketones,(E)-1,3-enones,and alkylbenzenes by chloramine-T(CAT)and N-chlorosuccinimide(NCS)under blue LED(...A practical photoinitiated synthetic method for the site-selectiveγ-andα-chlorination of C(sp^(3))-H bonds of ketones,(E)-1,3-enones,and alkylbenzenes by chloramine-T(CAT)and N-chlorosuccinimide(NCS)under blue LED(λ_(max)=456 nm)light irradiation is reported.Mechanistic studies suggest the reaction to proceed via a radical pathway where the chlorination reagent dichloramine-T(DCT)is generated in situ from the reaction of CAT with NCS.Its premised controlled formation along with that of the carbon-centered radical species derived from the substrate is thought to contribute to product site-selectivity.The developed protocol operates under mild reaction conditions at room temperature and demonstrates excellent functional group tolerance as exemplified by the site-selectiveγ-C(sp^(3))-H bond chlorination of carboxylic esters and amides,and late-stage functionalization of several bioactive natural products and drug molecules.The study also highlights the potential of CAT for the first time as a versatile and controllable chlorine radical atom source for site-selective halogenation reactions,expanding its synthetic utility beyond traditional applications.展开更多
基金supported by a Discovery Project Grant(DP250103974)from the Australian Research Council(to P.W.H.C.)and the German Science Foundation(KO5659/7-1,to R.M.K.).
文摘A practical photoinitiated synthetic method for the site-selectiveγ-andα-chlorination of C(sp^(3))-H bonds of ketones,(E)-1,3-enones,and alkylbenzenes by chloramine-T(CAT)and N-chlorosuccinimide(NCS)under blue LED(λ_(max)=456 nm)light irradiation is reported.Mechanistic studies suggest the reaction to proceed via a radical pathway where the chlorination reagent dichloramine-T(DCT)is generated in situ from the reaction of CAT with NCS.Its premised controlled formation along with that of the carbon-centered radical species derived from the substrate is thought to contribute to product site-selectivity.The developed protocol operates under mild reaction conditions at room temperature and demonstrates excellent functional group tolerance as exemplified by the site-selectiveγ-C(sp^(3))-H bond chlorination of carboxylic esters and amides,and late-stage functionalization of several bioactive natural products and drug molecules.The study also highlights the potential of CAT for the first time as a versatile and controllable chlorine radical atom source for site-selective halogenation reactions,expanding its synthetic utility beyond traditional applications.
