Stereoselective Organocatalytic Synthesis of Oxindoles with Adjacent Tetrasubstituted Stereocenters

Oxindoles with adjacent tetrasubstituted stereocenters were obtained in high yields and stereoselectivities by organocatalyzed conjugate addition reactions of monothiomalonates (MTMs) to isatin‐derived N‐Cbz ketimines. The method requires only a low catalyst loading (2 mol %) and proceeds under mild reaction conditions. Both enantiomers are accessible in good yields and excellent stereoselectivities by using either Takemoto’s catalyst or a cinchona alkaloid derivative. The synthetic methodology allowed establishment of a straightforward route to derivatives of the gastrin/cholecystokinin‐B receptor antagonist AG‐041R.     

Functional polymers. III. Asymmetric Michael reactions catalyzed by cinchona alkaloid–acrylonitrile copolymers

The enantio-differentiating abilities of cinchona alkaloid–acrylonitrile copolymers (AN–CA) in the Michael reactions were studied. The reaction of methyl indan-1-one-2-carboxylate (I) with methyl vinyl ketone in toluene at room temperature yielded product (II) in 24–42% optical yield, depending on the type and frequency of the alkaloid units on the polymeric skeleton. The catalysts were recovered from the reaction mixture by filtration and with retention of their stereoselectivities. Modification of the amino or hydroxyl group of the alkaloid moiety greatly reduced the reaction rate and optical yield. The asymmetric reactions of other donors (III–VII) with methyl vinyl ketone were also studied.     

Highly Diastereodivergent Synthesis of Tetrasubstituted Cyclohexanes Catalyzed by Modularly Designed Organocatalysts

A highly diastereodivergent synthesis of tetrasubstituted cyclohexanes has been achieved using modularly designed organocatalysts (MDOs) which are self‐assembled in situ from amino acids and cinchona alkaloid derivatives. Diastereodivergence is realized through controlling the stereoselectivity of the individual steps of a tandem Michael/Michael reaction. Up to 8 of the 16 possible stereoisomers have been successfully obtained in high stereoselectivities using MDOs for the tandem reaction and an ensuing epimerization. The method was used in the enantioselective synthesis of the natural products (?)‐α‐ and β‐lycoranes.     

Direct organocatalytic asymmetric alpha-sulfenylation of activated C-H bonds in lactones, lactams, and beta-dicarbonyl compounds

The application of cinchona alkaloid derivatives as catalysts for enantioselective alpha-sulfenylation of activated C-H bonds in lactones, lactams, and beta-dicarbonyl compounds by different electrophilic sulfur reagents is presented. Optically active products are obtained in good to excellent yields and up to 91 % ee. Furthermore, the diastereoselective reduction of alpha-sulfenylated beta-keto esters to give optically active alpha-sulfenylated beta-hydroxy esters has been studied. A model for the intermediate is presented, in which the protonated cinchona alkaloid interacts with the substrate leading to face-shielding in accordance with the enantioselective alpha-sulfenylation step.     

Enantioselective cyanocarbonation of ketones with chiral base

A highly enantioselective cyanocarbonation of dialkyl ketones catalyzed by commercially available and easily recyclable cinchona alkaloid derivatives has been developed. The reaction provides a useful approach for the enantioselective construction of tetrasubstituted carbon stereocenters. Mechanistic studies have been carried out to shed light on the origin of the catalytic activity of the cinchona alkaloid and the asymmetric induction step.     

合成金鸡纳生物碱衍生物的简便方法

以CaH2为缚酸剂,DMF为溶剂,金鸡纳生物碱通过3,6-二氯哒嗪或1,4-二氯-2,3-二氮杂萘桥连,高产率地合成了用作手性配体的13个金鸡纳生物碱衍生物,其结构经NMR确证.     

Enantioselective dichlorination of allylic alcohols

The development of an enantioselective allylic alcohol dichlorination catalyzed by dimeric cinchona alkaloid derivatives and employing aryl iododichlorides as chlorine sources is reported. Reaction optimization, exploration of the substrate scope, and a model for stereoinduction are presented.     

Scalable methodology for the catalytic, asymmetric alpha-bromination of acid chlorides

The optimization of a practical, catalytic, asymmetric process for the alpha-bromination of acid chlorides to produce synthetically versatile, optically active alpha-bromoesters is reported. A range of products is produced in high enantioselectivity and moderate to good chemical yields with retention of both upon scale-up. The reactions herein are catalyzed by cinchona alkaloid derivatives, with the best performance achieved by the use of a proline cinchona alkaloid conjugate designed in a de novo fashion.     

Organocatalytic asymmetric allylic alkylation of sulfonylimidates with Morita-Baylis-Hillman carbonates

The asymmetric allylic alkylation reaction of sulfonylimidates with various Morita-Baylis-Hillman (MBH) carbonates was accomplished by the catalysis of commercially available cinchona alkaloids catalyst (DHQD)2AQN.The corresponding allylic alkylation products were obtained in good yields with high stereoselectivities (up to 99% ee,89:11 dr).     

Role of the solvent in the adsorption-desorption equilibrium of cinchona alkaloids between solution and a platinum surface: correlations among solvent polarity, cinchona solubility, and catalytic performance

The role that the nature of the solvent plays in defining the extent of cinchona alkaloid adsorption-desorption equilibrium on platinum surfaces has been studied both by testing their solubility in 54 different solvents and by probing the stability of adsorbed cinchona in the presence of those solvents. The solubilities vary by as much as 5-6 orders of magnitude, display volcano-type correlations with solvent polarity and dielectric constant, and follow a cinchonine < cinchonidine < quinine, quinidine sequence. The adsorption-desorption equilibrium shifts toward the solution with increasing dissolving power of the solvent. The relevance of these results to the behavior of cinchona as chiral modifiers in hydrogenation catalysis is discussed.     

Computational studies of cinchona alkaloid-catalyzed asymmetric Michael additions

Cinchona alkaloids exhibit remarkable catalytic activities in a wide range of organic transformations. This review summarizes the recent advances of computational studies in understanding the mechanism and origins of enantioselectivities in cinchona alkaloid-catalyzed asymmetric Michael additions. Key activation model and controlling factors of reactivity and selectivity are elucidated.     

A Theoretical Investigation on the Strecker Reaction Catalyzed by a TiIV‐Complex Catalyst Generated from a Cinchona Alkaloid,Achiral Substituted 2,2′‐Biphenol,and Tetraisopropyl Titanate

The mechanism and the origin of selectivity of the asymmetric Strecker reaction catalyzed by a Ti^IV‐complex catalyst generated from a cinchona alkaloid, achiral substituted 2,2′‐biphenol, and tetraisopropyl titanate have been investigated by DFT and ONIOM methods. The calculations indicate that the reaction proceeds through a dual activation mechanism, in which Ti^IV acts as Lewis acid to activate the electrophile aldimine substrate, whereas the tertiary amine in cinchona alkaloid works as Lewis base to promote the activation and isomerization of HCN. The C? C bond formation step is predicted to be the selectivity‐controlling step in the reaction with an energy barrier of 9.3 kcal mol^?1. The “asymmetric activation” is achieved by the transfer of asymmetry from the chiral cinchonine ligand to the axially flexible achiral biphenol ligand through coordination interaction with the central metal Ti^IV. The large steric hindrance from the 3,3′‐position substitute of biphenol, combined with the quinoline fragment of cinchona alkaloid and the orientation of hydrogen bonding of iPrOH, play a key role in controlling the stereoselectivity, which is in good agreement with the experimental observations.     

有机小分子催化不对称Henry反应的研究进展

综述了各类有机小分子催化剂(如金鸡纳碱衍生物、手性(硫)脲、手性二级胺、金鸡纳碱-硫脲衍生物、胍-硫脲衍生物等)在不对称Henry反应中的研究进展。参考文献18篇。     

Asymmetric organocatalytic N-nitroso-aldol reaction of oxindoles

An organocatalytic enantioselective N-nitroso-aldol reaction of 2-oxindoles promoted by a cinchona alkaloid catalyst has been developed. The reaction shows exclusively N-selectivity, affording corresponding products with good to excellent yields (up to 100%) and moderate enantioselectivity. The regioselectivity of nitroso-aldol reaction being controlled by different cinchona catalysts was also observed.     

Enantioselective organocatalytic asymmetric allylic alkylation. Bis(phenylsulfonyl)methane addition to MBH carbonates

The highly enantioselective asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with bis(phenylsulfonyl)methane is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and enantioselectivities.     

Cyclodextrins as carriers for cinchona alkaloids: a pH-responsive selective binding system

A series of cyclodextrin-cinchona alkaloid inclusion complexes were prepared from beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin and four cinchona alkaloids in ca. 90% yields, and their inclusion complexation behavior was investigated at pH 7.2 and 1.5 by means of fluorescence, UV/Vis and 2D NMR spectroscopy. The results showed that the cinchona alkaloids can be efficiently encapsulated in the cyclodextrin cavity in an acidic environment and sufficiently released in a neutral environment, which makes these cyclodextrin derivatives the potential carriers for cinchona alkaloids. The binding ability and molecular selectivity of cyclodextrins toward cinchona alkaloids were discussed from the viewpoint of the size-fit concept and multiple recognition mechanism between host and guest.     

Enantioselective organocatalytic Michael addition reactions between N-heterocycles and nitroolefins

[reaction: see text] A method for Michael addition of N-heterocycles to nitroolefins has been developed. The process is promoted by a cinchona alkaloid derivative to give Michael adducts in moderate to high enantioselectivities.     

Recyclable cinchona alkaloid catalyzed asymmetric Michael addition reaction

A highly enantioselective and diastereoselective Michael addition reaction of α-fluoro-β-ketoesters with maleimides is catalyzed by fluorous cinchona alkaloid to afford two adjacent chiral centers. The catalyst attached with a perfluroalkyl tag can be recovered by fluorous solid-phase extraction (F-SPE).     

Cinchona alkaloid derived squaramide catalyzed diastereo- and enantioselective Michael addition of isocyanoacetates to 2-enoylpyridines

An efficient organocatalytic diastereo- and enantioselective Michael addition of α-substituted isocyanoacetates to 2-enoylpyridines catalyzed by cinchona alkaloid-derived squaramide has been achieved, affording the corresponding adducts with two adjacent tertiary-quaternary stereocenters in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >20:1 dr, up to 98% ee) under mild conditions.     

Asymmetric Mannich reactions catalyzed by cinchona alkaloid thiourea: enantioselective one-pot synthesis of novel β-amino ester derivatives

An efficient one-pot synthesis of novel β-amino ester derivatives containing a benzoxazol moiety has been developed by using cinchona alkaloid thioureas as the organocatalyst. The adducts were isolated in high enantiomeric excess and high yield.