Organocatalytic Enantioselective γ-Position-Selective Mannich Reactions of β-Ketocarbonyl Derivatives.

Catalytic asymmetric Mannich reactions of β-ketocarbonyl derivatives (such as β-ketoesters and (2-oxopropyl)phosphonate), resulting in the formation of a C-C bond at the γ-position of the β-ketocarbonyl derivatives with high enantioselectivities, are reported. The bond formation at the α-position of the β-ketoester was reversible, and the γ-position-reacted product δ-amino β-ketoester derivative was kinetically formed and was stable. The dynamic kinetic process was key for the direct access to the γ-position-reacted products from β-ketocarbonyls under catalytic conditions.

Control of Reactions of Pyruvates by Catalysts: Direct Enantioselective Mannich Reactions of Pyruvates Catalyzed by Amine-based Catalyst Systems.

Enantioselective Mannich reactions of pyruvates catalyzed by amine-based catalyst systems, in which pyruvates act as nucleophiles, are reported. The reactions of pyruvates and cyclic sulfonylimines afforded the desired Mannich products, including those bearing tetrasubstituted carbon centers, in high yields with high enantioselectivities in most cases. The selection of the acid used in the amine-based catalyst system was key for the formation of the Mannich products with high enantioselectivities.

MnO as a terminal oxidant in Wacker oxidation of homoallyl alcohols and terminal olefins.

Efficient and mild reaction conditions for Wacker-type oxidation of terminal olefins of less explored homoallyl alcohols to β-hydroxy-methyl ketones have been developed by using a Pd(ii) catalyst and MnO2 as a co-oxidant. The method involves mild reaction conditions and shows good functional group compatibility along with high regio- and chemoselectivity. While our earlier system of PdCl2/CrO3/HCl produced α,β-unsaturated ketones from homoallyl alcohols, the present method provided orthogonally the β-hydroxy-methyl ketones.

Direct Catalytic Asymmetric Synthesis of Oxindole-Derived δ-Hydroxy-β-ketoesters by Aldol Reactions.

Direct asymmetric synthesis of δ-hydroxy-β-ketoesters was accomplished via regio- and enantioselective aldol reactions of β-ketoesters with isatins catalyzed by cinchona alkaloid thiourea derivatives. The C-C bond formation of the reactions occurred only at the γ-position of the β-ketoesters. Reaction progress monitoring and product stability analyses under the conditions that included the catalyst indicated that the γ-position reaction products were formed kinetically.

Traceless OH-Directed Wacker Oxidation-Elimination, an Alternative to Wittig Olefination/Aldol Condensation: One-Pot Synthesis of α,β-Unsaturated and Nonconjugated Ketones from Homoallyl Alcohols.

A new method for one-pot synthesis of β-substituted and β,β-disubstituted α,β-unsaturated methyl ketones from homoallyl alcohols by sequential PdCl2/CrO3-promoted Wacker process followed by an acid-mediated dehydration reaction has been developed. Remarkably, internal homoallyl alcohols delivered regioselectively nonconjugated unsaturated carbonyl compounds under the same protocol. A new starting material-based synthesis of α,β-unsaturated and nonconjugated methyl ketones is demonstrated.