Synthesis of P-stereogenic compounds based on the diastereoselective ortho-lithiation of phosphinimidic amides

Abstract

The extension of the diastereoselective functionalization of the Ph2P group of C-chiral P,P-diphenyl phosphinimidic amides via directed ortho-lithiation (DoLi)-electrophilic quench reactions as a method for the preparation of structurally diverse P-stereogenic compounds is described. Transformations at both the phosphorus-containing and the ortho-functional groups provide access to a large variety of P-stereogenic derivatives with excellent stereocontrol. These transformations include aza-Wittig reactions, N-alkylations, methanolysis, nucleophilic displacements with Grignard reagents, phosphine oxide reductions, azide to amine conversions, halogen/metal exchange, and Suzuki cross-coupling and condensation reactions. These transformations increase the diversity of functional groups at the ortho-disubstituted phenyl ring and enable the synthesis of enantiopure ortho-formyl- and ortho-stannyl-phosphinic amides that are difficult to prepare by other methods. The new products synthesized might be used as building blocks for the construction of high value added P-stereogenic compounds. This is illustrated by the synthesis of [1,5,2]diazaphosphinin-6(5H)-one 21, a phosphazenylphosphinate (SPN,RPO)-22 and the analogues of relevant bidentate and tridentate privileged structures such as PHOX-like 23 and the heteroatomic N,O,P-tridentate ligand 25.