Regioselectivity in the ring-opening β-scission of 2-phenyl-1,3-dioxan-2-yl radicals derived from bicyclic benzylidene acetals

Abstract

The thiol-catalysed radical-chain redox rearrangement to benzoate esters of a number of cis- and trans-fused bicyclic benzylidene acetals derived from 1,3-diols has been investigated at ca. 130 °C in refluxing octane. The most generally effective and convenient combination of initiator and catalyst for this type of reaction consists of di-tert-butyl peroxide in conjunction with triisopropylsilanethiol. The benzoate esters are produced by β-scission of intermediate 2-phenyl-1,3-dioxan-2-yl radicals with fused cyclohexane or cyclopentane rings and there are two modes of cleavage for each radical, to give either a primary or a secondary 3-benzoyloxyalkyl radical. The regioselectivity of β-scission differs markedly depending on whether the ring junction is cis or trans, such that the trans-isomer gives preferentially the primary alkyl radical while the cis-isomer affords the secondary radical. Density functional calculations indicate that the β-scission proceeds through a product-like transition state in which the geometry at the emerging radical centre is quite close to planar. The regioselectivity observed in the β-scission of these bicyclic 1,3-dioxan-2-yl radicals can be understood in terms of the interplay between the thermodynamic driving force, charge-transfer stabilisation of the transition state and the degree of umbrella angle strain at the emerging radical centre.