The nucleophilic phosphinylation of alkyl halides with phosphonites,also known as Michaelis–Arbuzov phosphinylation,is a prominent method for synthesizing phosphinates;however,it is limited by high reaction temperatu...The nucleophilic phosphinylation of alkyl halides with phosphonites,also known as Michaelis–Arbuzov phosphinylation,is a prominent method for synthesizing phosphinates;however,it is limited by high reaction temperatures and primarily applicable to primary alkyl halides.Herein we present a radical approach to address the long-time challenges associated with nucleophilic phosphinylation.By employing 1 mol%1,2,3,5-tetrakis(diphenylamino)-4,6-dicyanobenzene as the catalyst,along with 20 mol%diisopropylethylamine and 150 mol%lithium benzoate as additives,satisfactory yields of desired alkyl(aryl)phosphinates are obtained through the reaction between alkyl bromides and dimethyl arylphosphonites under blue light irradiation at room temperature.The protocol is applicable to primary,secondary,and even structurally rigid tertiary alkyl bromides,and it can be extended to the phosphinylation of alkyl iodides.A radical–polar crossover mechanism involving alkyl radical addition to arylphosphonates and subsequent single-electron oxidation is proposed.展开更多
The Arbuzov reaction(also known as the Michaelis–Arbuzov reaction)is one of the most fundamental transformations in organic chemistry and has been extensively used for the synthesis of organophosphorus compounds for ...The Arbuzov reaction(also known as the Michaelis–Arbuzov reaction)is one of the most fundamental transformations in organic chemistry and has been extensively used for the synthesis of organophosphorus compounds for over a century.However,the reaction generally requires an elevated temperature and is applicable mainly to primary alkyl halides with poor functional group tolerance.We report herein a radical alternative to the conventional nucleophilic substitution reaction.Thus,new radical phosphonylation reagents,9-fluorenyl o-phenylene phosphite and benzhydryl o-phenylene phosphite,have been developed for this purpose.The photoredox-catalyzed reaction of a wide range of alkyl bromides or iodides with 9-fluorenyl(or benzhydryl)o-phenylene phosphite followed by workup with methanol(or ethanol)provides the corresponding dimethyl(or diethyl)alkylphosphonates in satisfactory yields at room temperature under mild conditions.The method is applicable to primary,secondary,and even tertiary alkyl iodides and bromides and exhibits an excellent functional group tolerance,thereby enabling the late-stage modification of complex molecules and rapid synthesis of phosphonate-containing natural products and drug molecules.A mechanism involving the formation and subsequentβ-scission of phosphoranyl radicals is proposed.展开更多
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB0590000)the National Natural Science Foundation of China(grant nos.22193010,22193014,and 21971253)+1 种基金the Chinese Academy of Sciences(grant no.ZDBS-LYSLH026)the Youth Promotion Association(grant no.2020257)of the Chinese Academy of Sciences,and the Science and Technology Commission of Shanghai Municipality(grant nos.21ZR1476700 and 21,YF1456300).
文摘The nucleophilic phosphinylation of alkyl halides with phosphonites,also known as Michaelis–Arbuzov phosphinylation,is a prominent method for synthesizing phosphinates;however,it is limited by high reaction temperatures and primarily applicable to primary alkyl halides.Herein we present a radical approach to address the long-time challenges associated with nucleophilic phosphinylation.By employing 1 mol%1,2,3,5-tetrakis(diphenylamino)-4,6-dicyanobenzene as the catalyst,along with 20 mol%diisopropylethylamine and 150 mol%lithium benzoate as additives,satisfactory yields of desired alkyl(aryl)phosphinates are obtained through the reaction between alkyl bromides and dimethyl arylphosphonites under blue light irradiation at room temperature.The protocol is applicable to primary,secondary,and even structurally rigid tertiary alkyl bromides,and it can be extended to the phosphinylation of alkyl iodides.A radical–polar crossover mechanism involving alkyl radical addition to arylphosphonates and subsequent single-electron oxidation is proposed.
基金the National Natural Science Foundation of China(grant nos.22193012,22193014,22122104,21933004,and 21971253)the Chinese Academy of Sciences(grant no.ZDBS-LY-SLH026)+1 种基金the Youth Promotion Association(grant no.2020257)the Chinese Academy of Sciences,and the Science and Technology Commission of Shanghai Municipality(grant nos.21ZR1476700 and 21YF1456300).
文摘The Arbuzov reaction(also known as the Michaelis–Arbuzov reaction)is one of the most fundamental transformations in organic chemistry and has been extensively used for the synthesis of organophosphorus compounds for over a century.However,the reaction generally requires an elevated temperature and is applicable mainly to primary alkyl halides with poor functional group tolerance.We report herein a radical alternative to the conventional nucleophilic substitution reaction.Thus,new radical phosphonylation reagents,9-fluorenyl o-phenylene phosphite and benzhydryl o-phenylene phosphite,have been developed for this purpose.The photoredox-catalyzed reaction of a wide range of alkyl bromides or iodides with 9-fluorenyl(or benzhydryl)o-phenylene phosphite followed by workup with methanol(or ethanol)provides the corresponding dimethyl(or diethyl)alkylphosphonates in satisfactory yields at room temperature under mild conditions.The method is applicable to primary,secondary,and even tertiary alkyl iodides and bromides and exhibits an excellent functional group tolerance,thereby enabling the late-stage modification of complex molecules and rapid synthesis of phosphonate-containing natural products and drug molecules.A mechanism involving the formation and subsequentβ-scission of phosphoranyl radicals is proposed.
