A DFT Perspective on Diels–Alder Organocatalysts Based on Substituted Phosphoramides

Abstract

Phosphoramides are an interesting alternative to the thiourea motif that has long been used in organocatalysis. In the R1N(H)‐P(O)(R3)‐N(H)R2 formulation, phosphoramides give the advantage of having a third variable substituent, R3, compared to the two available in thioureas, and the possibility of introducing chirality with an asymmetric phosphorus center. In this work, we present a systematic computational study on the catalytic properties of these underexplored compounds. These studies show the catalytic potential of a series of substituted phosphoramides in Diels–Alder reactions, including the asymmetric [4+2] cycloaddition of pro‐chiral substrates. The nature of the phosphorus‐bound R3 substituent has a significant impact both on catalytic activity and enantioselectivity. Remarkably, several of the phosphoramides studied are predicted to be more active than the Schreiner's thiourea organocatalyst.