Facile and highly enantioselective synthesis of (+)- and (-)-fluvastatin and their analogues

A highly enantioselective synthesis of (+)- and (-)-fluvastatin and their analogues has been facilitated by the reaction of an aldehyde with diketene in the presence of Ti(O-i-Pr)4 and a chiral Schiff base ligand. Either enantiomer of the Schiff base could be employed to obtain (+)- or (-)-fluvastatin. Diastereoselective reductions of the resultant keto moiety of β-hydroxy ketoesters provided the syn-1,3-diol esters (91% ee), which were subsequently recrystallized and saponified to afford (+)- and (-)-fluvastatin in >99.9% ee.