Stereocontrol in organic synthesis using silicon-containing compounds. A synthesis of methyl (+)-nonactate

Abstract

(3Z,2S)-7,7-Ethylenedioxyhex-3-en-2-yl N-phenylcarbamate 7 gave the allylsilane 8, (2E,4S)-7,7-ethylenedioxy-4-dimethyl(phenyl)silylhept-2-ene, introducing one stereogenic centre carrying a silyl group. Hydroboration–oxidation gave (2S,4S)-7,7-ethylenedioxy-4-dimethyl(phenyl)silylheptan-2-ol 9, controlling a second stereogenic centre. Conjugate addition of the phenyldimethylsilylcuprate reagent to the α,β-unsaturated imide (2′E,6′S,8′R,5S)-1-[8′-benzyloxy-6′-dimethyl(phenyl)silylnon-2′-enoyl]-5-triphenylmethoxymethylpyrrolidin-2-one 11 introduced a third stereogenic centre, and methylation of the ester derived from the product introduced a fourth. Ester hydrolysis and a double silyl-to-hydroxy conversion gave (2S,3S,6S,8R)-8-benzyloxy-3,6-dihydroxy-2-methylnonanoic acid 16, from which methyl (+)-nonactate 2 was prepared by differentiating the hydroxy groups with the selective formation of a β-lactone 17 rather than a seven-membered lactone.