Carbene-Catalyzed and Pnictogen Bond-Assisted Access to P^III-Stereogenic Compounds

Intermolecular pnictogen bonding (PnB) catalysis has received increased interest in non-covalent organocatalysis. It has been demonstrated that organic electron-deficient pnictogen atoms can act as prospective Lewis acids. Here, we present a catalytic approach for the asymmetric synthesis of chiral P^III compounds by combining intramolecular PnB interactions and carbene catalysis. Our design features a pre-chiral phosphorus molecule bearing two electron-withdrawing benzoyl groups, resulting in the formation of a σ-hole at the P atom. X-ray and non-covalent interaction (NCI) analysis indicate that the model substrates exhibit intrinsic PnB interaction between the oxygen atom of the formyl group and the phosphorus atom. This induces a conformational locking effect, leading to the crystallization of the phosphorus substrate in a preferred conformation (P2₁2₁2₁ chiral group). Under the catalysis of N-heterocyclic carbene, the aldehyde moiety activated by the pnictogen bond selectively reacts with an alcohol to yield the corresponding chiral monoester/phosphorus product with excellent enantioselectivity. This Lewis acidic phosphorus center, aroused by the non-polarized intramolecular pnictogen bond interaction, assists in conformational and selective regulations, providing unique opportunities for catalysis and beyond.