Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of (–)-tetrahydrolipstatin using the alkylation of a β-silyl ester and the hydroboration of an allylsilane

Abstract

Conjugate addition of bis(Z-tridec-1-enyl)cuprate Z-10 to (5S)-1-[(Z)-3′-dimethyl(phenyl)silylprop-2-enoyl]-5-(trityloxymethyl)pyrrolidin-2-one Z-6 gave the 3R-imide Z-12. Subsequent enolate n-hexylation of the benzyl ester Z-13a derived from this imide gave the 2R,3S-ester Z-14a. Reduction of the ester group and protection of the alcohol as its TBDMS group gave the allylsilane (Z)(7R,8S)-7-(tert-butyldimethylsilyloxymethyl)-8-dimethyl(phenyl)silylhenicos-9-ene Z-15. Hydroboration–oxidation gave the 7R,8S,10S-alcohol 16. Protection of the C-10 hydroxy as its benzyl ether, removal of the silyl protecting group and oxidation gave (2R,3S,5S)-5-benzyloxy-3-dimethyl(phenyl)silyl-2-hexylhexadecanoic acid 19. Silyl-to-hydroxy conversion, β-lactone formation, and hydrogenolysis gave the known alcohol (3S,4S)-3-hexyl-4-[(S)-2′-hydroxytridecyl]oxetan-2-one 22, from which tetrahydrolipstatin 1 was prepared by a conventional esterification. Each of the stereochemistry determining steps, 4 → Z-6, 7 → E-8, E-8 → Z-9, Z-6 + Z-10 → Z-12, Z-13a → Z-14a and Z-15 → 16, took place with a remarkably high level of open-chain stereocontrol.