Catalytic Asymmetric Protonation of Ketene Disilyl Acetals

Significance

Ooi and co-workers report the ­design of new chiral P-spiro diaminodioxaphosphonium barfates 2 and demonstrate their potential to catalyze enantioselective protonation reactions. In the presence of catalyst 2 (1 mol%) and 3 as stoichiometric proton source, the ketene disilyl ­acetals 1 were protonated in an enantioselective manner to give, after chromatography on silica gel, α-chiral α-amino acids 5 in quantitative yields and high enantioselectivities. The use of 4 (2 mol%) was found to be essential to ensure the reproducibility of high enantiomeric ratios.

Comment

The catalytic asymmetric synthesis of α-amino acids is an important task in chemical synthesis. The reported approach is based on the enantioselective protonation of amino acid-derived disilyl ketene acetals 1. In this transformation the newly designed catalyst 2 provides excellent results. However, due to the presence of 2 mol% of the bulky pyridine 4 the cata­lytically active species could also be the non-protonated iminophosphorane. This species may act as a bifunctional Brønsted acid-Lewis base catalyst donating a proton and accepting a TMS group from 1. In light of the fact that pyridines like 4 have previously been used to suppress Brønsted acid catalyzed pathways (B. Mathieu, L. Ghosez Tetrahedron 2002, 58, 8219), a bifunctional mechanism appears even more likely so that mechanistic studies would be desirable. None­theless, this method represents a powerful tool for the synthesis of optically active α-amino acids and is a nice demonstration of innovative catalyst design.