Catalytic Enantioselective Construction of Chiral ?-Azido Nitriles through Nitrile Group-Promoted Electrophilic Reaction of Alkenes

An efficient approach for the construction of enantioenriched ?-azido nitriles through the chiral sulfide-catalyzed asymmetric electrophilic thioazidation of allylic nitriles is disclosed. A wide range of electron-deficient and -rich aryl, heterocyclic aryl, and alkyl substituents are suitable on the substrates of allylic nitriles. The regio-, enantio-, and diastereo-selectivities of the reactions are excellent. As versatile platform molecules, the obtained chiral ?-azido nitriles can be easily converted into high-value-added chiral molecules that are not easily accessed by other methods. Control experiments revealed that the allylic nitrile group is important for control of the reactivity and enantioselectivity of the reaction leading to a broad substrate scope.

Automated summary

An efficient method for the synthesis of enantioenriched ?,?-azido nitriles through chiral sulfide-catalyzed asymmetric electrophilic thioazidation of allylic nitriles is reported. A wide range of substituents, both electron-deficient and -rich aryl, heterocyclic aryl, and alkyl groups, are suitable for the allylic nitrile substrates. The regio-, enantio-, and diastereo-selectivities of the reactions are excellent. The resulting chiral ?,?-azido nitriles can be easily converted into high-value-added chiral molecules that are not readily accessible by other methods, making them versatile platform molecules. Control experiments demonstrate the importance of the allylic nitrile group in controlling the reactivity and enantioselectivity of the reaction, leading to a broad substrate scope.