Optimisation, scope and limitations of enantioselective aldol reactions of an S-ketene silyl acetal with aliphatic aldehydes under (R)-BINOL-titanium(IV) catalysis conditions

The Mukaiyama aldol reaction between the functionalised aldehydes 5 and the S-ketene silyl acetal 2 catalysed by 1, 1'-binaphthyl-derived chiral titanium(iv) complex 4 afforded the corresponding aldol products 6 in good yields and with good to excellent enantioselectivities. The chemical yield could further be enhanced, without loss of stereoselection, by addition of phenol and/or molecular sieves. The presented aldol reactions with aluminium, boron and ytterbium-BINOL catalysts demonstrate that only low chiral induction can be achieved. Aldol product 6a was converted into an a-lipoic acid precursor 8, thus providing a formal synthesis of this biologically active compound. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.