Development of Efficient and Selective Synthetic Routes to Bio-active Compounds Using Reductive Method with Novel Redox Systems

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Novel synthetic methods, which are applicable to key reactions or provide a new route for the synthesis of bio-active compounds, have been developed on the basis of redox reactions.1) A new route to Patuolide A has been developed by using reductive deconjugation, which was also applied to the systematic synthesis of their derivatives bearing beta, gamma-unsaturated carbonyl group or gamma-oxo-(or hydroxy-) alpha, beta-unsaturated carbonyl group.2) Efficient usage of one-electron reduction with transition metals is considered to permit the development of novel synthetic method for radical reactions. gem-Dibromocyclopropanes underwent the highly stereoselective monodebromination based on one-electron reduction with low valent vanadium species. The reaction was found to proceed catalytically in the presence of zinc as a stoichiometric co-reductant. The presence of diethyl phosphonate is essential for this transformation. Low valent rare metals were capable of reducing gem-dibromocyclopropanes.3) An efficent process for the synthesis of Protease Inhibitor A-77003 is allowed by catalytic pinacol coupling. Cyclopentadienyl-substituted vanadium compounds were able to serve as such a catalyst in the presence of a stoichiometric amount of chlorosilane and zinc as a co-reductant. Use of THF as a solvent gave the desired diols, being in contrast to the formation of dioxolanes in dimethoxyethane. This finding provided an eficient method for reductive coupling since only dioxolane was produced by using the titanium catalyst. The diastereoselectivity depended on the steric effect of the starting aldehydes. The high dl diastereoselectivity was achieved in the vanadium-catalyzed pinacol coupling of sterically bulky aliphatic aldehydes.