Convenient Method for the Preparation of Carbamates, Carbonates, and Thiocarbonates

A convenient, rapid, and efficient method for the preparation of carbamates from amines with 1-alkoxycarbonyl-3-nitro-1,2,4-triazole transfer reagents is reported. Reactions of newly synthesized stable crystalline reagents with alkyl amines were completed in a few minutes without any additional base, and highly pure carbamates were obtained without chromatographic purification. These highly active reagents are also useful for the selective protection of nucleobases and preparation of carbonates and thiocarbonates

Mechanism of Palladium Complex-Catalyzed Enantioselective Mannich-Type Reaction: Characterization of A Novel Binuclear Palladium Enolate Complex

Studies on the enantioselective addition of enol silyl ethers to imines catalyzed by optically active palladium diaquo complexes 3 or binuclear palladium μ-hydroxo complex 4 are described, with particular focus on the mechanistic aspects. Asymmetric induction in the reaction using [Pd((R)-binap)(H2O)2]2+(BF4-)2 (3a) was quite sensitive to the reaction conditions, suggesting unfavorable effects of HBF4 generated from 3a in situ. Novel optically active binuclear μ-hydroxo complexes [{Pd((R)-binap)(μ-OH)}2]2+(BF4-)2 (4a), [{Pd((R)-tol-binap)(μ-OH)}2]2+(BF4-)2 (4b), [{Pd((R)-binap)(μ-OH)}2]2+(TfO-)2 (4c), and [{Pd((R)-tol-binap)(μ-OH)}2]2+(TfO-)2 (4d) were prepared and were found to be better catalysts for the asymmetric Mannich-type reaction. Benzoylalanine derivatives 5 were obtained in excellent chemical and optical yields (up to 90% ee). Mechanistic studies using 1H NMR and electrospray ionization mass spectrometry indicated that a unique binuclear palladium-sandwiched enolate 12 was involved in the reaction of enol silyl ether 1 with imine 2 catalyzed by 4

Aminotrifluoromethylation of Olefins via Cyclic Amine Formation: Mechanistic Study and Application to Synthesis of Trifluoromethylated Pyrrolidines

We examined the mechanism of our previously reported aminotrifluoromethylation reaction, which proceeds via intramolecular cyclization of alkenylamines in the presence of the combination of copper catalyst and Togni reagent (<b>1</b>). Kinetic studies revealed that the initial rate of the reaction was first order with respect to Togni reagent and CuI, as well as the substrate. Changes of the ¹⁹F NMR chemical shift of Togni reagent during the reaction suggested the existence of a dynamic equilibrium involving coordination of not only Togni reagent, but also the substrate amine and the product aziridine to copper. ESI-MS analysis provided evidence of involvement of reactive Cu­(II) intermediates in the catalytic cycle. Overall, our results indicate that the reaction proceeds at the hypervalent iodine moiety of Togni reagent, which is activated by Cu­(II) species acting as a Lewis acid catalyst. On the basis of these mechanistic considerations, we developed an efficient synthesis of trifluoromethylated pyrrolidine derivatives. This transformation exhibited a remarkable rate enhancement upon addition of Et₃N

Enantioselective Addition of Enol Silyl Ethers to Imines Catalyzed by Palladium Complexes: A Novel Way to Optically Active Acylalanine Derivatives

Enantioselective Addition of Enol Silyl Ethers to Imines Catalyzed by Palladium Complexes:  A Novel Way to Optically Active Acylalanine Derivative

Direct Generation of Nucleophilic Chiral Palladium Enolate from 1,3-Dicarbonyl Compounds: Catalytic Enantioselective Michael Reaction with Enones

Generation of chiral palladium enolates from 1,3-dicarbonyl compounds with the palladium aqua complex and its application to the highly efficient catalytic enantioselective Michael reaction with enones are described. The palladium aqua complexes are likely to supply Brønsted base and Brønsted acid successively during the reaction. The former activates the carbonyl compounds to give chiral palladium enolates, and the latter cooperatively activates enones. Using a catalytic amount (2−10 mol %) of the palladium complexes, the various 1,3-dicarbonyl compounds including diketones and β-ketoesters were converted to the desired Michael adducts in good yields (69−92%) with excellent enantiomeric excesses (89−99% ee)

Aminotrifluoromethylation of Olefins via Cyclic Amine Formation: Mechanistic Study and Application to Synthesis of Trifluoromethylated Pyrrolidines

We examined the mechanism of our previously reported aminotrifluoromethylation reaction, which proceeds via intramolecular cyclization of alkenylamines in the presence of the combination of copper catalyst and Togni reagent (<b>1</b>). Kinetic studies revealed that the initial rate of the reaction was first order with respect to Togni reagent and CuI, as well as the substrate. Changes of the ¹⁹F NMR chemical shift of Togni reagent during the reaction suggested the existence of a dynamic equilibrium involving coordination of not only Togni reagent, but also the substrate amine and the product aziridine to copper. ESI-MS analysis provided evidence of involvement of reactive Cu­(II) intermediates in the catalytic cycle. Overall, our results indicate that the reaction proceeds at the hypervalent iodine moiety of Togni reagent, which is activated by Cu­(II) species acting as a Lewis acid catalyst. On the basis of these mechanistic considerations, we developed an efficient synthesis of trifluoromethylated pyrrolidine derivatives. This transformation exhibited a remarkable rate enhancement upon addition of Et₃N

A New Entry to Pd−H Chemistry: Catalytic Asymmetric Conjugate Reduction of Enones with EtOH and a Highly Enantioselective Synthesis of Warfarin

We report here the catalytic asymmetric conjugate reduction of enones using ethanol as a hydride source. The reaction was carried out in the presence of a chiral Pd complex at ambient temperature in ethanol, and the desired products were obtained in high chemical yield and high enantioselectivity. We applied this novel reaction to the catalytic asymmetric synthesis of warfarin (96% ee), and on the basis of d-labeling experiments, the reaction mechanism is proposed

Aminotrifluoromethylation of Olefins via Cyclic Amine Formation: Mechanistic Study and Application to Synthesis of Trifluoromethylated Pyrrolidines

We examined the mechanism of our previously reported aminotrifluoromethylation reaction, which proceeds via intramolecular cyclization of alkenylamines in the presence of the combination of copper catalyst and Togni reagent (<b>1</b>). Kinetic studies revealed that the initial rate of the reaction was first order with respect to Togni reagent and CuI, as well as the substrate. Changes of the ¹⁹F NMR chemical shift of Togni reagent during the reaction suggested the existence of a dynamic equilibrium involving coordination of not only Togni reagent, but also the substrate amine and the product aziridine to copper. ESI-MS analysis provided evidence of involvement of reactive Cu­(II) intermediates in the catalytic cycle. Overall, our results indicate that the reaction proceeds at the hypervalent iodine moiety of Togni reagent, which is activated by Cu­(II) species acting as a Lewis acid catalyst. On the basis of these mechanistic considerations, we developed an efficient synthesis of trifluoromethylated pyrrolidine derivatives. This transformation exhibited a remarkable rate enhancement upon addition of Et₃N

Mechanism of Palladium Complex-Catalyzed Enantioselective Mannich-Type Reaction: Characterization of A Novel Binuclear Palladium Enolate Complex

Studies on the enantioselective addition of enol silyl ethers to imines catalyzed by optically active palladium diaquo complexes 3 or binuclear palladium μ-hydroxo complex 4 are described, with particular focus on the mechanistic aspects. Asymmetric induction in the reaction using [Pd((R)-binap)(H2O)2]2+(BF4-)2 (3a) was quite sensitive to the reaction conditions, suggesting unfavorable effects of HBF4 generated from 3a in situ. Novel optically active binuclear μ-hydroxo complexes [{Pd((R)-binap)(μ-OH)}2]2+(BF4-)2 (4a), [{Pd((R)-tol-binap)(μ-OH)}2]2+(BF4-)2 (4b), [{Pd((R)-binap)(μ-OH)}2]2+(TfO-)2 (4c), and [{Pd((R)-tol-binap)(μ-OH)}2]2+(TfO-)2 (4d) were prepared and were found to be better catalysts for the asymmetric Mannich-type reaction. Benzoylalanine derivatives 5 were obtained in excellent chemical and optical yields (up to 90% ee). Mechanistic studies using 1H NMR and electrospray ionization mass spectrometry indicated that a unique binuclear palladium-sandwiched enolate 12 was involved in the reaction of enol silyl ether 1 with imine 2 catalyzed by 4

Catalytic Asymmetric Synthesis of Halenaquinone and Halenaquinol

Catalytic Asymmetric Synthesis of Halenaquinone and Halenaquino