Polystyrene-immobilized pyrrolidine as a highly stereoselective and recyclable organocatalyst for asymmetric Michael addition of cyclohexanone to nitroolefins

Polystyrene-immobilized pyrrolidine 4 has been developed as a highly efficient, reusable, and stereoselective organocatalyst for the asymmetric Michael addition of cyclohexanone to nitroolefins. In the presence of trifluoroacetic acid, 4 catalyzed the reaction of cyclohexanone to a variety of nitroolefins with high yields (up to >99%) and excellent diastereoselectivities (up to >99:1 dr), and enantioselectivities (up to >99% ee). Furthermore, 4 could be recovered and recycled by a simple filtration of the reaction solution and used for more than 10 consecutive trials without significant loss of its catalytic activity.     

Asymmetric domino Michael–Henry reaction of 1,2-diones with nitroolefins catalyzed by a chiral bisoxazolidine–Ni(acac)2 complex

The asymmetric domino Michael–Henry reaction of 1,2-cyclohexadione with nitroolefins catalyzed by chiral ligand bisoxazolidine 1 and Ni(acac)₂ has been developed. This process provided highly functionalized chiral bicycle[3,2,1] octane derivatives with the generation of four new stereogenic centers in high yields (76–99%), and with excellent enantioselectivities (up to 99%) and good diastereoselectivities (up to 9:1) under mild reaction conditions. The procedure presented is simple and makes this method suitable for practical use.     

A highly enantioselective organocatalyst for the Michael addition of cyclic ketones to nitroolefins

Enantiomerically pure triamine 2, which catalyses the Michael addition of cyclic ketones to nitroolefins with high diastereoselectivity (up to 99:1) and enantioselectivity (up to 91% ee), was designed and prepared.     

Asymmetric Michael addition of aldehydes to nitroolefins catalyzed by l-prolinamide derivatives using phenols as co-catalysts

The asymmetric Michael addition of aldehydes to nitroolefins was investigated using l-prolinamide derivatives of 2-(2′-piperidinyl)pyridine as catalyst and a variety of phenols as co-catalyst. Extensive screening toward the effect of prolinamides, phenols, and solvents on this transformation revealed that a combination of (S)-2-(2′-piperidinyl)pyridine-derived trans-4-hydroxy-l-prolinamide 2c, (S)-1,1′-bi-2-naphthol, and dichloromethane was a promising system. This system was shown to be amenable to a rich variety of aldehydes and nitroolefins and afforded the nitroaldehyde products with excellent yield, enantiomeric excess (up to 99%) and diastereoselectivity ratio (up to 99/1), even in the case of 1 mol % catalyst loading and 1.5 equiv of aldehydes.     

A new type of organocatalyst for highly stereoselective Michael addition of ketones to nitroolefins on water

(S)-2-((Naphthalen-2-ylsulfonyl)methyl)pyrrolidine, prepared in three steps from (S)-N-Boc-2-[((4-toluenesulfonyl)oxy)methyl]pyrrolidine in 62% overall yield, was used as a new type of organocatalyst bearing a pyrrolidine and a sulfone moiety. It shows very high catalytic activity toward the direct asymmetric Michael reaction of cyclohexanone and nitroolefins. All the corresponding adducts can be furnished in 90-99% yields and with up to 98% ee and over 99:1 dr on water in the presence of this catalyst (15 mol %) without any additive.     

Novel chiral ammonium ionic liquids as efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins

Two chiral ammonium ionic liquids 1a and 1b have been newly synthesized from commercially available (+)-cis-2-benzamidocyclohexanecarboxylic acid. These CILs have been demonstrated to be efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins with excellent yields (up to 99%), high enantioselectivities (up to 90%) and modest to high diastereoselectivities (syn/anti ratio up to 99/1).     

Highly enantioselective Michael addition of ketones to nitroolefins catalyzed by (S)-pyrrolidine arenesulfonamide

A new type of catalyst for the asymmetric Michael addition reaction has been designed and synthesized. This catalyst, (S)-pyrrolidine arenesulfonamide 1, resulted in high yields (up to 93%), excellent diastereoselectivities (syn/anti ratio up to 99/1), and excellent enantioselectivities (ee up to 99%) for various cyclic ketones and nitroolefins.     

Chiral 2-aminobenzimidazole bifunctional organocatalysts: effect of di-CF3 and TFA on catalytic mechanisms

(S,S)-trans-Cyclohexanediamine-5,7-di-CF₃-benzimidazole (3b) was developed as a new chiral bifunctional organocatalyst and successfully applied to Michael addition of diethyl malonate to nitroolefins (up to 99%, 98% ee) under neutral condition. Systematic investigation on the catalytic mechanism revealed that the role of the guanidine moiety and the dimethylamine moiety in catalysts might be reversed with respect to Brønsted/Lewis acidic or basic functionalities, depending on the reaction conditions (neutral or TFA co-catalyst). Generally, di-CF₃ group substituted 2-aminobenzimidazole catalysts in neutral condition and non-substituted 2-aminobenzimidazole catalysts in co-catalyst (TFA) condition give high chemical yield and enantioselectivity.     

Recyclable C2-symmetric tertiary amine-squaramide organocatalysts: Design and application to asymmetric synthesis of γ-nitrocarbonyl compounds

Simple C₂-symmetric chiral tertiary amines bearing squaramide fragments along with the 1,2-di(pyridin-2-yl)ethane spacer group have been synthesized. Among them, amine 8b with a different configuration of stereocenters in 1,2-di(pyridin-2-yl)ethane and 1,2-diaminocyclohexane units efficiently catalyzed asymmetric additions of β-dicarbonyl compounds to nitroolefins and domino reaction of ortho-(tosylamino)chalcone with β-nitrostyrene in wet (20 equiv. of H₂O) DCM, affording corresponding adducts in up to 99% yield and 94% ee. The developed procedure is scalable. Due to poor solubility in organic solvents and water, the catalyst could be readily separated from the reaction mixture and over 10 times reused in the reaction without compromising enantiomeric enrichment and yield of product.     

Highly efficient bifunctional organocatalysts for the asymmetric Michael addition of ketones to nitroolefins

A type of secondary-secondary-tertiary triamine bifunctional organocatalysts have been properly designed and synthesized. In our study, the designed catalyst (S)-N-(pyrrolidin-2-ylmethyl)pyridin-2-amine 5 has been shown to be highly efficient to promote the asymmetric Michael addition of ketones to nitroolefins at room temperature, which afforded the corresponding adducts in excellent diastereoselectivities (up to 99:1 dr) and enantioselectivities (up to >99% ee).     

Simple amphiphilic isosteviol–proline conjugates as chiral catalysts for the direct asymmetric aldol reaction in the presence of water

Two novel amphiphilic catalysts 3 and 4 were synthesized by the condensation of isosteviol with l-proline in a one-pot process. With only 1 mol % loading, the catalyst 3 showed excellent activity (up to >99% yield) and stereoselectivity (up to 99:1 dr, >99% ee) for the direct aldol reaction of cyclohexanone and substituted benzaldehydes at room temperature in the presence of water. In addition, solvent effects, catalyst loading, substrate scope, temperature, and the influence of water on the reactions were investigated. These results demonstrate that the catalysts with a chiral concave and hydrophobic substituent in the 4-position of l-proline furnished high activity and stereoselectivity for the reaction.     

L-丙氨酰Betti碱催化环己酮对硝基烯不对称Michael加成反应

合成了3个手性Betti碱的L-丙氨酰衍生物, 并用它们来催化环己酮与硝基烯的Michael加成反应. 发现1a是其中最有效的催化剂, ee值最高大于99%, dr值最高大于99∶1. 考察了催化剂结构与用量、添加剂用量、底物结构等因素对反应的化学产率和光学收率的影响.     

Ionic-liquid-supported organocatalyst for the enantioselective Michael addition of ketones to nitroolefins

Ionic-liquid-supported triazole-pyrrolidine 2, for the direct asymmetric Michael reaction was successfully synthesized. The supported catalyst demonstrated good activity and high enantioselectivity in the addition of cyclohexanone to nitroolefins. Furthermore, the supported catalyst can be readily recovered and reused four times without significant loss of catalytic activity.     

Synthesis of air-stable mixed bis-carboxylate titanocene complexes and their catalytic behaviors in cross-aldol and Mannich reactions

Tunable organometallic Lewis acid catalysts were developed by combining salicylic acid (H₂-Sal) with benzoic acid (H-Ben), 4-fluorobenzoic acid (H-BenF) and 3-thiophenic acid (H-Th), as coligands for mixed bis-carboxylate titanocene complexes. Three air-stable complexes [Cp₂Ti(η¹-HSal)(η¹-Ben)] (1), [Cp₂Ti(η¹-HSal)(η¹-BenF)] (2) and [Cp₂Ti[η¹-HSal][(η¹-Th)] (3) were prepared in high yields by the reaction of salicylato titanocene chelate with carboxylate ligands. The mixed bis-carboxylate titanocene complexes were fully characterized by physicochemical and spectroscopic methods. Single-crystal X-ray diffraction studies revealed Ti–O_(H-Sal) bond distances in 1, 2 and 3 of 1.972(3), 1.9245(18) and 1.912(5) Å, respectively, while the bond distances involving the coligands of 1, 2 and 3 are 1.908(3) Å (Ti–O_Ben), 1.9296(19) Å (Ti–O_BenF) and 1.945(5) Å (Ti–O_Th), respectively. These bis-carboxylate titanocene complexes showed satisfactory activities and selectivities in Mannich and cross-aldol reactions. Notably, complex 3 bearing the labile thiophene carboxylate ligand gave high yields with a diastereomer ratio (d.r.) as high as 1:99 for the direct Mannich reactions of benzaldehyde, cyclohexanone and aniline. In cross-aldol reaction of benzaldehyde and cyclohexanone, 1 and 2 successfully catalyzed the formation of double-aldol products in up to 99 % yield.     

Proline-based dipeptides with two amide units as organocatalyst for the asymmetric aldol reaction of cyclohexanone with aldehydes

A series of proline-based dipeptide organocatalysts with two amide units (1-16) have been developed and evaluated in the direct catalytic asymmetric aldol reactions of aldehydes with cyclohexanone. These catalysts showed good solubility in organic solvents compared with their corresponding carboxyl terminal dipeptides. The robust amide bond formation allowed structural modifications and fine tuning of catalyst properties by varying the stereo and electronic effects of the terminal amide to affect the ability of hydrogen bonding formation between the catalysts and the substrates. The reactions proceeded smoothly in high yields (up to 99%), enantioselectivities (up to 98% ee) and anti-diastereoselectivities (up to 99:1) in the presence of bifunctional organocatalyst 4 under the optimal reaction conditions.     

The highly enantioselective bifunctional organocatalysts for the Michael addition of сyclohexanone to titroolefins

A new family of organocatalyst derived from proline has been developed and shown to be an efficient catalyst for asymmetric Michael addition of cyclohexanone to nitroolefins with high diastereo- and enanthio -selectivities. (syn: anti ratio up to 99:1, ee. up to 95%.). The result of computational studies at the B3LYP/6-31G* level indicate that both the hydrogen bonding and the stereo hindrance play the crucial role in the activation of the nitro alkene and help to discriminate between the two diastereofacial approaches.     

Chiral pyrrolidine quaternary derivatives as organocatalysts for asymmetric Michael additions

A series of chiral pyrrolidine quaternary derivatives were designed and synthesized. It was found that these derivatives are highly efficient organocatalysts for the asymmetric Michael addition reactions of aldehydes and ketones to nitroolefins with high yields (up to 96%), high enantioselectivities (up to 99% ee), and high diastereoselectivities (up to 97:3 dr). Furthermore, catalyst 7a could be recycled without remarkable loss of catalytic activity and stereoselectivity.     

Asymmetric Michael addition catalysed by sugar-based prolinamides in solvent-free conditions

Sugar-based prolinamides derived from glucosamine have been developed as organocatalysts for the asymmetric Michael addition between cyclohexanones and nitroolefins. Numerous polar and nonpolar solvents and additives have been screened in the current study. The organocatalyst 1c in the presence of benzoic acid as additive catalysed the reaction under neat conditions to afford Michael adducts in high yields (up to 98%) with excellent diastereoselectivities (up to >99:1) and moderate enantiomeric ratios (up to 84:16).     

Extrusion reactions-VII

ω-(2,6-Dimethyl-4-pyrimidinylthio-(4), 2-methyl-4-quinazolinylthio-(9), and 4-oxo-2-quinazo-linylthio)-(10) acetophenones with hydrochloric or perchloric acid provide 2,5-diaryl-1,4-dithiins (7) whereas α)-(6-methyl-4-pyrimidinylthio) acetophenones (11) with aq HCl/HClO₄, or POCl₃ followed by hydrolysis provide 1-(4-aryl-2-thiazolyl)-2-propanones (12). Likewise, 2-(6-methyl-4-pyrimidinylthio) cyclohexanone (13) give the thiazole derivative (14).     

Michael reaction of ketones and β-nitrostyrenes catalyzed by camphor-10-sulfonamide-based prolinamide

Novel camphor sulfonamide based organocatalysts were evaluated for their catalytic activity in the Michael reaction of ketones with nitroolefins. Reaction of ketones with β-nitrostyrenes in the presence of 20 mol % organocatalyst 1a and benzoic acid under solvent-free conditions at 0 °C provided the desired Michael adducts with high chemical yields (up to 97%) and excellent stereoselectivities (>99:1).