(2S,5S)-5-(Methylamino)-4,4-diphenyl-1,3,2-dioxaphosphorinane-2-oxide as a preligand in palladium-catalyzed asymmetric allylic alkylation

Abstract

A P-chiral oxygen-substituted secondary phosphine oxide was synthesized from the bicyclophosphoramidite precursor using a straightforward method without participation of bases and aggressive phosphorus trihalides. Its use in the Pd-catalyzed asymmetric allylic alkylation (AAA) of (E)-1,3-diphenylallyl acetate and (E)-1,3-diphenylallyl ethyl carbonate with dialkyl malonates provided up to 62% ee with predominant formation of (R)-products. It was shown that, when N,O-bis(trimethylsilyl)acetamide (BSA) and KOAc were used as a combined base, the true inducer of chirality was a P(III)-trimethylsilyl derivative formed by the reaction of the oxygen-substituted phosphine oxide with an excess of BSA in the reaction medium. The starting bicyclic phosphoramidite provided the opposite sign of asymmetric induction in the alkylation of (E)-1,3-diphenylallyl acetate with dimethyl malonate and afforded a significantly lower enantiomeric excess (22% (S)). The P(III)-trimethylsilyl compound and its Pd(II) allyl complexes were obtained in situ and characterized by NMR spectroscopy and high-resolution mass spectrometry.