Synthesis of β,N-diphosphoryl-substituted α-aminocinnamates via the C,N-diphosphorylation of 2H-azirines.

Abstract

A method for the synthesis of β,N-diphosphoryl-substituted α-aminocinnamates from 2-bromo-2H-azirine-2-carboxylic esters and trimethyl or triethyl phosphite has been developed. The transformation affords the target phosphoramidates in generally high yields across a broad range of 3-aryl-substituted azirines. A reaction mechanism, supported by DFT calculations, includes a five-step domino process involving two phosphite molecules: the first effects the Michaelis-Arbuzov phosphorylation of the azirine via SN2'-substitution of bromine, whereas the second promotes opening of the azirine ring through attack at the CN bond, ultimately leading to the diphosphorylated α-aminocinnamate. The found transformation represents the first example of N-phosphorylation by a trialkyl phosphite.