Studies on the Development of Novel Asymmetric Multi-Functional MPV Reduction

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The introduction of a thiol group into a chiral alcohol regent for asymmetric Meerwein-Ponndorf-Verley (MPV) reductions allows asymmetric reduction of α,β-unsaturated ketones to secondary alcohols and allylic alcohols via a novel tandem Michael addition/MPV reduction. The reaction of acyclic α,β-unsaturated ketones and (-)-10-mecaptoisoborneol using dimethylaluminum chloride afforded the MPV reduction products diastereoselectively in very high yields (up to 96%). Mechanistic studies elucidated : (1) the structure of the chelation complex with (-)-isoborneol and dimenthylalumium chloride, (2) an asymmetric 1,7-hydride shift, and 3) dynamic kinetic resolution via reversible Michael addition. Subsequent reductive desulfurization of the MPV products with a modified Raney nickel system led to the highly enantioselective reduction of α,β-unsaturated ketones to saturated secondary alcohols in 96-98% ee. β-Elimination of the corresponding sulfoxides gave the allylic alcohols in 86-98% ee. Appl … More ications to the asymmetric reduction of a synthetic intermediate of prostaglandins and to a new asymmetric synthesis of the (+)-Rove beetle pheromone was developed.Optically active 1,3-mercapto alcohol were synthesized from α,β-unsaturated ketones using (-)-2-mercaptomethylisoborneol in two steps. The transformation involved the above tandem reaction and a base catalyzed elimination. The two newly created carbons in tras-chalcone derivatives were enantioselectively controlled to a high degree. Using the above transformation, an asymmetric bifunctional group exchange reaction between the substrate and chiral reagent was developed.A highly asymmetric protonation of Michael addition of thiol to α-substituted α,β-unsaturated esters using a chiral mercapto alcohol was found. Subsequent cleavage of the chiral auxiliary from the product would formally furnish an asymmetric Michael addition of hydrogen sulfide to α-substitute α,β-unsaturated esters. In the tandem reaction of α-substituted α,β-unsaturated ketones, configurations of the newly generated three sequential carbons were also highly controlled. However, attempts to remove the chiral auxiliary from the product are unsuccessful to far. Less