Biscyclophanes. Part 2: Regioselectivity in the acid-catalysed cycloalkylation of benzylbenzylic alcohol (BBA)

Abstract

o-Benzylbenzylic alcohols (o-BBAs), in which the terminal benzyl alcohol is substituted by repeating benzyl chains all in the ortho sense, have been found to have conspicuous regioselectivity in acid catalysed cycloalkylation, giving rise to various cyclophanes as intramolecular Friedel–Crafts alkylation products. The structure of the cyclisation products was largely dependent upon the size of the benzylic alcohols. Acidic treatment of 2-nuclear o-BBA 6 gave a [1.1]orthocyclophane 7 with a 6-membered ring, whereas 3-nuclear o-BBA 1 afforded [1.1.1]orthocyclophane 2 with a 9-membered ring in preference to a 6-membered-ring product. Higher homologues, such as 4- and 5-nuclear o-BBAs, gave rise to [1_·4](1,2)(1,2)(1,2)(1,3)cyclophanes 14 and 25 with a 13-membered ring unit, respectively. Cyclophanes with a larger-than-1 3-membered ring have never been isolated as cycloalkylation products of o-BBA. Generalisations have been made about the priority of formation of cycles in the cycloalkylation of o-BBA in acid, to give a cycloalkylation rule, which involves the priority order of 13-membered ring > 9-membered ring > 6-membered ring. The regioselectivity was consistent with the acid-catalysed cycloalkylation of α,ω-benzylbenzylic diols, which yielded common-nuclear biscyclophanes. The sizes and structures of the biscyclophane products are also dependent upon the sizes and structures of the terminal benzylic diols.