The 3,4-dihydro-2H-pyran approach to (+)-milbemycin β3. Part 1. An alternative synthesis of (2S,4S,6R,8R,9S)-2-formylmethyl-4-(dimethyl-t-butylsilyloxy)-8,9-dimethyl-1,7-dioxaspiro[5.5]undecane

Abstract

A more efficient synthesis of the title compound (12), previously used in a total synthesis of (+)-milbemycin β₃(2), is described. The key step in the sequence involves a nucleophilic cleavage of the oxirane (33) by the organocuprate (28) derived from metallation of (2R,3S)-2,3-dimethyl-3,4-dihydro-2H-pyran (26).