β-Halogeno ether synthesis of olefinic alcohols: stereochemistry and conformation of 2-substituted 3-halogenotetrahydro-pyran and -furan precursors

Abstract

Ring-scission of cis- or trans-2-alkyl-(or aryl-) 3-chlorotetrahydropyrans proceeds regioselectively and highly stereoselectively to give (E)-alk-4-en-1-ols, but in the parallel tetrahydrofuran series (Z)-/(E)-mixtures, dependent on precursor geometry, are formed. In this paper the stereochemistry and conformation of the tetrahydro-pyran and -furan precursors are considered. The cis/trans-composition of 2,3-dihalogenotetrahydro-pyrans and -furans made by various routes is reported. Reaction with Grignard reagents gives separable cis-/trans-mixtures the stereoisomeric composition of which, in the cases examined, does not depend on the stereoisomeric composition of the dihalide, but does vary with the halogen and the composition of the Grignard or dialkylmagnesium; possible reasons are discussed.The stereochemistry and conformation of the 2-alkyl-(or aryl-)3-chlorotetrahydropyrans is analysed by n.m.r. methods (J2a,3ecis ca. 1.5 Hz; J2a,3atrans ca. 9.8 Hz) but assignments for the two tetrahydrofuran series with J2.3 2.6–3.6 and 4.3–5.9 are made uncertain by pseudorotation. The stereochemical identity of the two series is rigorously proved by isolation of cis- and trans-2-allyl-3-chlorotetrahydrofuran. On the one hand the former is hydrogenated to the cis-2-propyl compound, correlated with other members of the alkyl series, but on the other it is oxidised and the acid is converted into the cis-p-bromophenacyl ester. The stereochemistry and conformation of the latter is rigorously demonstrated by an X-ray structure.The stereochemistries and conformations of the 2-deuterio- and 2-methoxy-3-chlorotetrahydropyrans are discussed, and consideration is then extended to the 2-alkyl-3-chloro-2-methyltetrahydro-pyran and -furan series.