anti-Selective direct asymmetric Mannich reactions catalyzed by chiral pyrrolidine-based amino sulfonamides

The novel pyrrolidine-based amino sulfonamides (R,R)-2, (S)-3, and (S)-4 were designed and synthesized as organocatalysts and successfully applied for the anti-selective direct asymmetric Mannich reaction.     

syn-Selective asymmetric cross-aldol reactions between aldehydes and glyoxylic acid derivatives catalyzed by an axially chiral amino sulfonamide

syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl glyoxylate and glyoxamide were realized by the use of an axially chiral amino sulfonamide (S)-1. The cross-aldol products obtained are densely functionalized and readily converted to synthetically useful and important chiral building blocks such as γ-lactone and γ-lactam.     

Anti-selective direct asymmetric Mannich reaction catalyzed by protease

The anti-selective direct asymmetric Mannich reaction of (hetero) aromatic aldehydes, 4-anisidine and O-protected hydroxyacetones for the synthesis of stereodefined anti-β-amino-α-hydroxycarbonyl compounds was developed. Protease type XIV from Streptomyces griseus (SGP) was used as a biocatalyst in 1,4-dioxane/phosphate buffer under mild reaction conditions. The excellent diastereoselectivities of up to >99:1 (anti/syn) and good enantioselectivities of up to 90% ee were achieved. This method provides a more sustainable complement to chemically catalyzed anti-selective direct asymmetric Mannich reactions.     

Acyclic β-amino acid catalyzed asymmetric anti-selective Mannich-type reactions

The ability of a primary amine containing acyclic β³-amino acids to catalyze direct asymmetric anti-selective Mannich-type reactions is presented. The reactions are generally highly diastereo- and enantioselective to give the corresponding Mannich products with up to >19:1 dr (anti/syn) and 88–99% ee.     

Design of a C2-symmetric chiral pyrrolidine-based amino sulfonamide: application to anti-selective direct asymmetric Mannich reactions

The anti-selective direct asymmetric Mannich reaction was found to be efficiently catalyzed by the novel pyrrolidine-based amino sulfonamide (R,R)-2 prepared from l-tartaric acid.     

Direct asymmetric hydroxyamination reaction catalyzed by an axially chiral secondary amine catalyst

A direct asymmetric hydroxyamination reaction of aldehydes with nitrosobenzene was found to be catalyzed by the novel axially chiral secondary amine catalyst (S)-1d. The resulting optically enriched hydroxyamination products were readily converted to beta-amino alcohols or 1,2-diamines in one pot.     

Direct asymmetric aminoxylation reaction catalyzed by a binaphthyl-based chiral amino sulfonamide with high catalytic performance

A binaphthyl-based amino sulfonamide (S)-2 was applied to the direct asymmetric aminoxylation of aldehydes with nitrosobenzene. The reaction catalyzed by (S)-2 proceeded smoothly to give the aminoxylated product in good yield with excellent enantioselectivity. This method represents a rare example of the highly enantioselective aminoxylation by a non-proline type catalyst with high catalytic performance.     

Highly diastereoselective and enantioselective direct organocatalytic anti-selective Mannich reactions employing N-tosylimines

Organocatalytic direct anti-selective Mannich reactions of O-TBS-hydroxyacetone with various N-tosylimines derived from aromatic aldehydes in the presence of L-threonine-derived catalyst afforded 1,2-amino alcohols in good yields and with enantioselectivities of 99% in almost all cases.     

Direct asymmetric three-component organocatalytic anti-selective Mannich reactions in a purely aqueous system

The direct three-component Mannich reactions of O-benzyl hydroxyacetone with p-anisidine and aromatic or aliphatic aldehydes in the presence of an L-threonine-derived catalyst afforded anti-1,2-amino alcohols in good-to-excellent yields and with enantioselectivities of up to 97%. This study is the first demonstration that direct three-component Mannich reactions can be promoted by a primary amino acid in water.     

Highly anti-selective asymmetric nitro-mannich reactions catalyzed by bifunctional amine-thiourea-bearing multiple hydrogen-bonding donors

Highly anti-selective and enantioselective nitro-Mannich reactions have been achieved for a broad spectrum of substrates catalyzed by chiral bifunctional multiple hydrogen-bonding-donor amine-thioureas. Multiple hydrogen-bonding donors play a significant role in accelerating reactions and improving yields, diastereoselectivities, and enantioselectivities.     

Highly enantioselective Mannich reactions of imines with tert-butyl acetoacetate catalyzed by squaramide organocatalyst

Highly enantioselective Mannich reactions of imines bearing a benzothiazole moiety with tert-butyl acetoacetate, catalyzed by a cinchona-based squaramide organocatalyst have been developed. The corresponding benzothiazole β-keto ester derivatives were obtained in high yields (up to 99%) and with excellent enantioselectivities (up to 98% ee).     

Enantioselective direct Mannich reactions of 3-substituted oxindoles catalyzed by chiral phosphine via dual-reagent catalysis

A combination of an amino acid-derived chiral phosphine catalyst and methyl acrylate to catalyze the direct Mannich reaction of 3-substituted oxindoles and imines has been reported to afford 3-tetrasubstituted oxindole derivatives which are key structures for biological activities. The products are formed with a quaternary carbon and featured with two adjacent chiral centers. Various N-EDG(electron-donating group) and N-EWG(electron-withdrawing group) protected oxindoles, including 3-aryl and 3-alkyl substituted ones, have been evaluated with aromatic and aliphatic imines under this catalytic system, smoothly giving desired products in good yields as well as excellent diastereo- and enantioselectivities.     

Catalytic asymmetric synthesis of axially chiral o-iodoanilides by phase-transfer catalyzed alkylations

Catalytic asymmetric synthesis of axially chiral o-iodoacrylanilides and N-allyl-o-iodoanilides as useful chiral building blocks was achieved via chiral quaternary ammonium salt-catalyzed N-alkylations under phase-transfer conditions. The transition-state structure for the present reaction is discussed on the basis of the X-ray crystal structure of ammonium anilide.     

Acyclic amino acid-catalyzed direct asymmetric aldol reactions: alanine, the simplest stereoselective organocatalyst

The linear amino acid-catalyzed direct asymmetric intermolecular aldol reaction is presented; simple amino acids such as alanine, valine, isoleucine, aspartate, alanine tetrazole and serine catalyzed the direct catalytic asymmetric intermolecular aldol reactions between unmodified ketones and aldehydes with excellent stereocontrol and furnished the corresponding aldol products in up to 98% yield and with up to > 99% ee.     

Design and synthesis of a biphenyl-based chiral amino sulfonamide with high catalytic performance in Mannich reactions

A biphenyl-based amino sulfonamide was designed to improve the intrinsic low catalytic activity of amine organocatalysts. The newly synthesized amino sulfonamide catalyst promoted the Mannich reaction in a highly enantioselective fashion and a remarkable catalyst turnover number was achieved.     

Direct asymmetric aldol reactions catalyzed by a siloxy serine organocatalyst in water

A siloxy-l-serine organocatalyst has been developed to catalyze direct asymmetric aldol reactions in the presence of water, furnishing the β-hydroxy carbonyl scaffold in high enantio- and diastereoselectivities. The direct aldol reaction between a selection of aromatic aldehydes and cyclohexanone resulted in good yields and high enantioselectivities.     

Double axially chiral bisphosphorylimides as novel Brønsted acids in asymmetric three-component Mannich reaction

A double axially chiral bisphosphorylimide has been demonstrated to be an efficient and highly sterically hindered Brønsted acid in asymmetric three-component Mannich reactions. Optically active syn-β-amino ketones were obtained in high yields (up to 99%) with excellent diastereoselectivity (99:1) and enantioselectivity (up to 99% ee). A gram-scale reaction was also performed to prove the synthetic application value of this reaction.