Development of P-stereogenic 2-phenyl-1,3,2-oxazaphosphorine ligands and their unexpected sensitivity to oxidation

Abstract

P-Stereogenic oxazaphosphorine compounds of the form 4 have not previously been reported as asymmetric ligands for metal-catalyzed reactions. In an effort to explore the behavior of such oxazaphosphorine ligands, monomeric oxazaphosphorine borane 9 and dimeric oxazaphosphorine boranes 25 and 26 were synthesized as catalyst precursors. The absolute configuration of the phosphorus center contained in the oxazaphosphorines was determined by X-ray crystallography. Rhodium-catalyzed hydrogenation of methyl 2-acetamidoacrylate using a dimerized spiro oxazaphosphorine ligand was performed with up to 15% ee. The extreme sensitivity of the oxazaphosphorine ligands toward oxidation prevented further optimization of the enantioselectivity.