Catalytic and stoichiometric Lewis acid participation in aldehyde ene cyclisations

Racemic 2-isopropyl-2-methylhex-5-enal has been synthesised in order to probe ene cyclisations leading to menthol analogues. The objective was first to discover catalytic conditions for preferential cyclisation to the menthol rather than the neomenthol series and then to develop (dynamic) kinetic resolution procedures which afforded a single enantiomer of product. It was found that catalytic quantities of both Me2AlCl and a bulky methylaluminium bis(phenoxide) reagent gave products attributed to a Meerwein-Pondorff-Verley reaction. In this the aldehyde is reduced to a primary alcohol and the ene product oxidised to the corresponding a,P-unsaturated ketone. By contrast, a related bulky chloroaluminium reagent catalysed the ene cyclisation cleanly, but preferentially to the undesired neomenthyl stereoisomer.