Cyano-borrowing: titanium-catalyzed direct amination of cyanohydrins with amines and enantioselective examples.

The direct amination of cyanohydrins with amines via a catalytic cyano-borrowing reaction was developed. The transformation features broad substrate scope, excellent functional group compatibility, and very mild and simple operations. Moreover, a titanium catalyst supported by quinine and (S)-BINOL ligands enabled an asymmetric cyano-borrowing reaction with moderate to high enantioselectivity.

Titanium-Catalyzed Cyano-Borrowing Reaction for the Direct Amination of Cyanohydrins with Ammonia.

α-Aminonitrile was an important building block in natural products and key intermedia in organic chemistry. Herein, the direct amination of cyanohydrins with the partner of ammonia to synthesis N-unprotected α-aminonitriles is developed. The reaction proceeds via titanium-catalyzed cyano-borrowing reaction, which features high atom economy and simple operation. A broad range of ketone or aldehyde cyanohydrins was tolerated with ammonia, and the N-unprotected α-aminonitriles were synthesis with moderate to high yields under mild reaction conditions.

Cyano-borrowing reaction: nickel-catalyzed direct conversion of cyanohydrins and aldehydes/ketones to ß-cyano ketone.

A direct nickel-catalyzed, high atom- and step-economical reaction of cyanohydrins with aldehydes or ketones via an unprecedented "cyano-borrowing reaction" has been developed. Cleavage of the C-CN bond of cyanohydrins followed by aldol condensation and conjugate addition of cyanide to α,ß-unsaturated ketones proceeded to deliver a range of racemic ß-cyano ketones with good to high yields. The practical procedure with the use of a commercial and less-toxic CN source bodes well for wide application of this protocol.

The roles of benzoic acid and water on the Michael reactions of pentanal and nitrostyrene catalyzed by diarylprolinol silyl ether.

The roles of benzoic acid and water on the Michael reaction of pentanal and nitrostyrene catalyzed by diarylprolinol silyl ether are revealed by density functional theory calculations. The calculations demonstrate that the benzoic acid is ready to attack the catalysts and form a hydrogen bond between the hydrogen atom of the COOH of benzoic acid and one of the N atoms of the catalyst. The complex formed from pentanal, catalyst and benzoic acid attacks nitroalkene and forms transition states. Finally, the transition states hydrolyze and the products are formed. The calculations demonstrate that the stereoselectivity is dominated by the steric hindrance of the 2-substituent groups, and the benzoic acid can increase the reaction rate evidently by decreasing the activation energies; however, H(3)O(+) or strong acid may prevent the formation of the transition states between enamines and nitroalkenes. The employed solvent can decrease the activation energies and promote the proton transfer from benzoic acid onto the catalyst 2. The calculated enantiomeric excess values are in good agreement with the experimental results. These calculations also reveal that the role of benzoic acid is dependent on the sophisticated structures of the catalysts and provide a valuable index for the structural design of new catalysts and selection of additives or co-catalysts.

Enantioselective and solvent-controlled diastereoselective Mannich reaction of isatin imines with hydroxyacetone: synthesis of 3-substituted 3-aminooxindoles.

The diastereoselectively switchable enantioselective Mannich reaction of isatin imines with hydroxyacetone is reported. The chiral primary amino acid catalyzed this Mannich reaction to afford both anti- and syn-Mannich adducts in high yields, good diastereoselectivities, and enantioselectivities. The reason for the solvent control of the diastereoselectivity phenomenon was investigated.

A systematic study of chiral homoprolinols and their derivatives in the catalysis of enantioselective addition of diethylzinc to aldehydes.

Homoprolinol analogs, a class of optically active γ-amino alcohols, were examined systematically in the enantioselective addition reactions of diethylzinc to aldehydes. By comparison of the results catalyzed by these γ-amino alcohols with those by the ß-amino alcohols based on pyrrolidine architecture reported in the literature references, we have observed that the γ-amino alcohols are superior to the corresponding ß-amino alcohols when the nitrogen and the oxygen are unsubstituted. Among the homoprolinols we tested, gave the best results (45-88% yields, 44-81% ee) in the addition reactions. To the best of our knowledge, has been noticed as one of the most efficient γ-amino alcohol catalysts based on pyrrolidine framework.

A facile direct anti-selective catalytic asymmetric Mannich reaction of aldehydes with preformed N-Boc and N-Cbz imines.

Anti-selective Mannich reactions of N-Boc and N-Cbz protected imines with unmodified aldehydes proceeded smoothly under the catalysis of a secondary amine-thiourea catalyst, which led to high yields (70%-95%) and excellent enantioselectivity (up to 96 : 4 dr and >99% ee) under conventional organic synthetic operations.

Highly enantioselective alkylation reaction of enamides by Brønsted-acid catalysis.

The H8-BINOL-derived, phosphoric acid catalyzed, highly enatioselective alkylation reaction of enamides with indolyl alcohols has been described. A phosphoric acid derived from H8-BINOL enabled an asymmetric alpha-alkylation of enamides with indolyl alcohols to give beta-aryl 3-(3-indolyl)propanones in high yields (up to 96%) and with excellent enantioselectivity (up to 96% ee).