Synthesis of cyclohexenols and cycloheptenols via the regioselective reductive ring opening of oxabicyclic compounds

Abstract

The reductive ring opening of oxabicyclic compounds has been achieved. While RMgBr/MgBr2 works in a few limited substrates, diisobutylaluminum hydride reacts with oxabicyclic[3.2.1]- and -[2.2.1]alkenes to provide cycloheptenols and cyclohexenols in good yield and in some cases in good regioselectivity. With some substrates further reduction of the alkene was observed which led us to examine transition metals such as nickel which are known to accelerate the hydroalumination reaction. The reaction with Ni(COD)2 (COD = cyclooctadiene) gave the best reactivity-selectivity profile, and significantly higher yields were obtained with minimal overreduction of the alkene. Phosphine ligands were shown to dramatically improve the regioselectivity of ring opening of bridgehead-substituted oxabicyclic compounds. The best ligand was 1,4-bis(diphenylphosphino)butane which gave up to 380:1 selectivity. A series of deuterium quenching experiments showed that the selectivity of the hydroalumination varies according to the reaction protocol and ligand-metal ratio.