Condensed cyclic and bridged-ring systems. Part III. Regioselectivity and stereoselectivity in the acid-catalysed cyclisations of substituted benzylcyclohexanols. Stereocontrolled synthesis of some gem-carboxy–methyl-substituted hexahydrofluorene and hexahydro-5,9-methanobenzocyclo-octene derivatives

Abstract

Treatment of ethyl 2-benzyl-2-hydroxy-1,3-dimethylcyclohexanecarboxylate (8) with polyphosphoric acid produced either (±)-c-2-benzyl-1,3-dimethylcyclohexane-r-1,c-3-carbolactone (6) or a mixture from which (1RS,4aRS,9aRS)2,3,4,4a,9,9a-hexahydro-1,4a-dimethyl-1H-fluorene-1-carboxylic acid (5a) was isolated in a moderate yield, depending upon the reaction temperature. Whereas aluminium chloride-catalysed cyclisation of the lactone (6) resulted in the stereospecific formation of (5SR,8RS,9SR,11RS)-5,6,7,8,9,10-hexahydro-8,11-dimethyl-5,9-methanobenzocyclo-octene-8-carboxylic acid (9), the epimeric t-2-benzyl lactone (7) produced a mixture of the hexahydrofluorene acid (5a) and the epimeric (8SR)-hexahydromethanobenzocyclo-octene acid (12), in high yields. By a similar process (±)-methyl t-2-benzyl-t-3-hydroxy-1,3-dimethylcyclohexane-r-1-carboxylate (4) gave the acid (9) and a mixture of hexahydrofluorene ester (5b) and (8SR)-hexahydromethanobenzocyclo-octene (13). Structures and configurations of the bridged-ring compounds were determined from chemical and n.m.r. spectral studies. Ready alkaline hydrolysis of the tertiary ester group in (5SR,8RS,9SR,11SR)-methyl 5,6,7,8,9,10-hexahydro-8,11-dimethyl-10-oxo-5,9-methanobenzocyclo-octene-8-carboxylate (11), through intramolecular oxo-group participation, revealed the stereochemistry of the ester group. The observed differences in the nature of products in polyphosphoric acid-catalysed cyclisation of (8) and the behavioural differences shown by the diastereoisomeric lactones (6) and (7) and the hydroxy-ester (4) in aluminium chloride-induced cyclisations are rationalised on the basis of steric and stereoelectronic factors in the intermediate cations as well as the thermodynamic stability of the products under reversible reaction conditions.