β-Halogeno-ether synthesis of olefinic alcohols: stereochemistry of the ring-scission of 2-substituted 3-halogenotetrahydro-pyrans and -furans

Abstract

The stereochemical outcome of the sodium ring-scission of 2-substituted 3-halogenotetrahydro-pyrans and -furans, with 2-substitution represented by alkyl, alkenyl or aryl, is presented. Although the cis- and the trans-tetrahydropyran scissions are highly stereoselective for (E)-5-substituted pent-4-enols, this stereoselectivity breaks down when the 2-substituent is conformationally undiscriminating (deuterium) or has substantial anomeric effects (methoxy). Consideration of this, along with conformational data from the preceding paper, provides an explanation of the stereoselectivity of the tetrahydropyran scission. Evidence against a radical, and for a carbanion intermediate is presented and a common, very rapidly inverting, 3-carbanion is considered to be formed from either cis- or trans-stereoisomers. Ring scission is also rapid (the carbanion cannot be trapped), but less rapid than carbanion inversion, and takes place before the slower conformational inversion can occur so that the (E)/(Z)-nature of the unsaturated alcohol produced is controlled by the initial tetrahydropyran conformation. The unstereospecific nature of the ring scission of both cis- and trans-2-alkyl-3-chlorotetrahydrofurans is explained as a consequence of their existence in conformational equilibria.

The high stereoselectivity of the ring scission of cis- and trans. 3-chloro-2,3-dimethyltetrahydropyrans, and the poor stereoselectivity of the scission of 2-alkyl-2-3-chloro-2-methyltetrahydropyrans, is explained; the reaction of sodium with 2-butyl-3,3-dichlorotetrahydropyran is considered. Using the ring-scission of 3-chloro-2-ethyltetrahydropyran, short syntheses of (±)-exo-and (±)-endo-brevicomin are described to illustrate the utility of β-halogen ether synthesis.