Enhanced reactivity and anti selectivity in the asymmetric Lewis acid-mediated Mukaiyama aldol reaction of α-alkoxythiolketene acetals with α,β-disubstituted enals: synthesis of the C26–C33 segment of rapamycin

Abstract

The tin(II)-mediated reaction of α-alkoxythiolketene acetals 3a–d with trans-2-methylbut-2-enal and aldehyde 10 was found to give enhanced reactivity and high anti selectivity in the glycolate product when an α-benzyloxy substituent was present in 3, a finding which was applied to the synthesis of a segment (C26–C33) of the immunosuppressant rapamycin.