A synthesis of (±)-lavandulol using a silyl-to-hydroxy conversion in the presence of 1,1-disubstituted and trisubstituted double bonds

Abstract

Silylcuprates and silylzincates react with α,β-unsaturated aldehydes, esters, ketones and amides 19 unsubstituted at the β-position in higher yield if trimethylsilyl chloride is present. Applying this method, conjugate addition of the silylcuprate 26 derived from (Z)-chloro(2-methylbut-2-enyl)diphenylsilane 24, itself prepared by an improved route, to 3-methylene-6-methylhept-5-en-2-one 25 gave 3-[(Z)-2-methylbut-2-enyl(diphenyl)silyl]methyl–6-methylhept-5-en-2-one 27. A Wittig reaction gave 3-[(Z)-2-methylbut-2-enyl(diphenyl)silyl]methyl–2,6-dimethylhepta-1,5-diene 28 and silyl-to-hydroxy conversion gave lavandulol 1, even in the presence of the 1,1-disubstituted and trisubstituted double bonds. The hydroxy group of the 3-hydroxysilane, 2,6-dimethyl-3-{[(Z)-2-methylbut-2-enyl]diphenylsilyl}methylhept-5-en-2-ol 30, activated the allylsilane group towards protodesilylation. Chloro(diphenyl)methallylsilane 35 is easier to make than the chloride 24, and should be an alternative allylsilane that can make a lithium and hence a cuprate reagent like 26.