I. Spiro Asymmetric Induction: Synthesis Of Optically Pure Alpha-hydroxy- And Alpha,beta-dihydroxy Acid Derivatives. Ii. Oxidative Electrolysis Of Gamma-ketal Cyclohexanecarboxylic Acids: Total Synthesis Of Malyngolide.

Abstract

I. A new and efficient method for the preparation of optically pure (alpha)-hydroxy and (alpha),(beta)-dihydroxy acid derivatives has been developed. Ketalization of easily accessible chiral cyclohexanones (3-methylcyclohexanone, menthone, 8-phenylmenthone) with glycolic acid affords spiro 1,3-dioxolan-4-ones as a chromatographically separable mixture of two diastereomers in each case. Deprotonation of each isomer followed by alkylation or aldol condensation of these glycolate enolates provides (alpha)-hydroxy or (alpha),(beta)-dihydroxy esters after acidic ethanolysis. The chiral ketone is recovered in good yield from the ethanolysis. The absolute stereochemistry of these products is a consequence of which diastereomeric 1,3-dioxolan-4-one is chosen initially. Syn/anti diastereoselection in the aldol condensation is a function of metal cation (Li('+) and Mg('++) give anti, Zr('+4) affords syn). Thus, any stereoisomer of an (alpha),(beta)-dihydroxy ester is available in a rational way. II. An effective method for carbon-carbon bond fragmentation through the oxidative electrolysis of 1-nonyl-3-oxo-cyclohexanecarboxylic acid ethylene ketal has been developed. The fragmentation product, methyl 5-nonyl-5-hexenoate, serves as the key intermediate for the synthesis of marine antibiotic malyngolide in four steps.