Origins of enantioselectivity in reductions of ketones on cinchona alkaloid modified platinum

A model to explain the stereoselectivities of reductions of activated ketones on cinchona alkaloid modified platinum is proposed and is supported by calculations by density functional and force field methods. The model involves nucleophilic catalysis by the cinchona alkaloid. The zwitterionic adduct between a cinchona alkaloid and ketone is adsorbed on Pt through the quinoline ring and two heteroatoms and is subsequently reduced with inversion. The model rationalizes the observed stereoselectivities for hydrogenation of carbonyl compounds.     

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 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.     

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.     

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.     

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.     

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.     

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).     

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.     

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.     

Synthesis of helical poly(phenylacetylene)s bearing cinchona alkaloid pendants and their application to asymmetric organocatalysis

Four novel dynamic helical poly(phenylacetylene)s bearing cinchona alkaloids as pendant groups were synthesized starting from the commercially available cinchona alkaloids, cinchonidine, cinchonine, quinine, and quinidine, by the polymerization of the corresponding phenylacetylene monomers with a rhodium catalyst. These polymers exhibited an induced circular dichroism (ICD) in the UV–visible region of the polymer backbones in solution, resulting from the preferred‐handed helical conformation induced by the optically active cinchona alkaloid pendants. In response to the solvent used, their Cotton effect patterns and intensities were significantly changed accompanied by the changes in their absorption spectra probably due to the changes in their helical conformations, such as the inversion of the helical sense or helical pitch of the polymers. When these helical polymers were used as polymeric organocatalysts for the asymmetric conjugated addition and Henry reactions, the optically active products with a modest enantiomeric excess were obtained whose enantioselectivities were comparable to those obtained with the corresponding cinchona alkaloid‐bound monomers as the catalysts. However, we observed a unique enhancement of the enantioselectivity and a reversal of the stereoselectivity for some helical polymers, suggesting the important role of the helical chirality during the asymmetric organocatalysis. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Organocatalytic enantioselective nucleophilic vinylic substitution by alpha-substituted-alpha-cyanoacetates under phase-transfer conditions

The organocatalytic enantioselective formation of vinyl-substituted all-carbon quaternary stereocenters via nucleophilic vinylic substitution by alpha-substituted-alpha-cyanoacetates is presented. The reaction proceeds well for different alpha-substituted-alpha-cyanoacetates and beta-chloroalkenones using a dimeric cinchona alkaloid phase-transfer catalyst giving the products in good yield and with enantioselectivities up to 98% ee.     

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.     

Asymmetric Mannich reaction of dicarbonyl compounds with alpha-amido sulfones catalyzed by cinchona alkaloids and synthesis of chiral dihydropyrimidones

The highly enantioselective cinchona alkaloid-catalyzed Mannich reaction of dicarbonyl compounds with alpha-amido sulfones as acyl imine precursors is described. The reaction requires 10 mol % of the cinchona alkaloid catalyst, which serves as a general base to generate acyl imines in situ, and aqueous Na2CO3 to maintain the concentration of free alkaloid catalyst. The reaction products are obtained in good yields and high enantioselectivities, and in diastereoselectivities that range from 1:1 to >95:5. The cinchonine-catalyzed reactions provide practical access to highly functionalized building blocks which have been employed in the synthesis of chiral dihydropyrimidones, a class of compounds rich in diverse biological activity. Dihydropyrimidone modifications include a highly diastereoselective hydrogenation of the enamide moiety, using an H-Cube flow hydrogenator and a Rh(II)-mediated 1,3-dipolar cycloaddition to afford highly functionalized complex heterocycles.     

Enantioselective <Emphasis Type="Italic">O</Emphasis>-allylic alkylation of Morita-Baylis-Hillman carbonates with oxime

The enantioselective O-allylic alkylation of acetophenone oxime with various Morita-Baylis-Hillman (MBH) carbonates has been accomplished by the catalysis of a commercially available cinchona alkaloid (DHQD)2PHAL. The corresponding O-allylic products were obtained in moderate to excellent yields up to 96% ee.     

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.     

Asymmetric conjugate addition of azide to α,β-unsaturated nitro compounds catalyzed by cinchona alkaloids

The cinchona alkaloid catalyzed asymmetric addition of azide to α,β-unsaturated nitro compounds giving optically active β-azido nitro compounds in high yields and with low enantioselectivity is presented. Subsequent modifications allow for the formation of chiral 1,2-diamines.     

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.     

Enantioselective synthesis of α-deuterium labelled chiral α-amino acids via dynamic kinetic resolution of racemic azlactones

Catalytic dynamic kinetic resolution (DKR) of racemic azlactones with EtOD using squaramide-based dimeric cinchona alkaloid organocatalysts is shown to be a highly effective strategy for the preparation of enantiomerically pure α-deuterated chiral α-amino acids.