Asymmetric allyltributylstannane addition to ketones catalyzed by chiral PYBOX-In(III) complex immobilized in ionic liquid

An indium complex of chiral PYBOX was applied in the catalytic asymmetric allylation of ketones in the ionic liquid. It was found that this chiral indium complex was strong enough to promote the reaction of ketones with allyltributylstannane smoothly. The products were obtained in moderate to high enantioselectivities, and the chiral catalyst immobilized in the ionic liquid could be reused with comparable enantioselectivities and yields.     

Catalytic asymmetric vinylation and dienylation of ketones

A solution to the long-standing problem of catalytic asymmetric vinylation of ketones is reported. Vinylzinc reagents are generated via hydrozirconation of terminal alkynes followed by transmetalation to zinc. In the presence of our catalyst, which is formed in situ from a bis(sulfonamide) diol ligand (1) and titanium tetraisopropoxide, the vinylzinc reagent undergoes 1,2-addition to a variety of ketones and enones with enantioselectivities (typically >90%) and high yields. This method is tolerant of functional groups, including alkyl, aryl and vinyl halides, esters, silyl protected alcohols, sulfides, and alkenes. Thus, enantioenriched tertiary allylic alcohols bearing a variety of functional groups can be prepared. It has also been found that 2,2-disubstituted vinylzinc reagents, substitution patterns not accessible through hydrozirconation, can be added to ketones with high enantioselectivities to generate trisubstituted allylic alcohols. Furthermore, we have developed an asymmetric addition of dienyl groups to ketones in the presence of our catalyst. This method enables the synthesis of dienols in high yields with enantioselectivities as high as 94%.     

Enantioselective alkynylation of carbonyl compounds with trimethoxysilylalkynes catalyzed by lithium binaphtholate

Enantioselective alkynylation of aldehydes and ketones was accomplished using trimethoxysilylalkynes as alkynylating reagents and lithium 3,3′-diphenylbinaphtholate as a catalyst. Optically active propargylic alcohols were obtained in good to high chemical yields and enantioselectivities. Alkynylation of acetylpyridines afforded biologically active pyridyl propargylic alcohols in good enantioselectivities.     

Chiral [RuCl2(dipyridylphosphane)(1,2‐diamine)] Catalysts: Applications in Asymmetric Hydrogenation of a Wide Range of Simple Ketones

The dipyridylphosphane/diamine–Ru complex combined with tBuOK in 2propanol acts as a very effective catalyst system for the enantioselective hydrogenation of a diverse range of simple ketones including heteroaromatic ketones, substituted benzophenones, alkenyl ketones, and cyclopropyl ketones. The combination of desirable features, such as quantitative chemical yields within hours, broad substrate scope, excellent enantioselectivities (up to 99 %), and high substrate‐to‐catalyst ratios, among others, makes the present catalyst system of high practical interest.     

New and efficient catalysts for enantioselective borohydride reduction of ketones and imines

Optically active aldiminato cobalt(II) complexes have been found to catalyze the enantioselective reduction of ketones with sodium borohydride affording the corresponding optically active secondary alcohols in high chemical yields with high enantioselectivities. The enantioselective borohydride reduction is also applicable to not only C=O bonds in aromatic ketones but also to C=N bonds in aromatic imines.     

Diastereoselective and enantioselective capture of chiral zinc enolate using nitroolefins: a rapid access to chiral γ-nitro carbonyl compounds

Highly diastereoselective and enantioselective catalytic capture of chiral zinc enolates using nitroolefins as electrophiles is described. The tandem products γ-nitro ketones were obtained in good yields with high diastereoselectivities and enantioselectivities. The γ-nitro ketones were readily hydrogenated to the optically enriched and diastereomerically pure chiral pyrrolidines with four contiguous stereocentres under mild conditions.     

Silver-catalyzed asymmetric Sakurai-Hosomi allylation of ketones

The complex of AgF and (R)-DIFLUORPHOS has been shown to be an effective catalyst for the asymmetric Sakurai-Hosomi allylation of simple ketones. A significaant improvement of the reactivity was observed by using THF as the solvent. The catalyst turnover was increased by addition of 1 equiv of MeOH. AgF and (R)-DIFLUORPHOS predominantly formed a 1:1 complex that provided high enantioselectivity. This catalyst system can be applied to various simple ketones, and corresponding tertiary homoallylic alcohols were obtained with excellent enantioselectivities (up to 96% ee). Only 1,2-adducts were obtained from both acyclic and cyclic conjugate ketones. The regio-, diastereo-, and enantioselective crotylation has also been achieved. E- or Z-crotyltrimethoxysilane gave a similar diastereomer ratio with high enantioselectivities. This finding introduces the utility of racemic allylsilanes for the enantioselective Sakurai-Hosomi allylation reaction.     

Enantioselectively organocatalytic Michael addition of ketones to alkylidene malonates

An organocatalytic asymmetric Michael addition of ketones to alkylidene malonates has been developed. In the presence of 20 mol % of urea 1a or N-(pyrrolidin-2-ylmethyl)trifluoromethanesulfonamide 1j, the reactions of ketones with alkylidene malonates afford the desired Michael adducts in moderate to good yields with good to high enantioselectivities under mild conditions.     

Catalytic asymmetric methallylation of ketones with an (H8-BINOLate)Ti-based catalyst

The first catalytic asymmetric methallylation of ketones is reported. The catalyst, which is generated from titanium tetraisopropoxide, H8-BINOL, 2-propanol, and tetramethallylstannane, reacts with ketones in acetonitrile to afford tertiary homoallylic alcohols in fair to excellent yields (55-99%) and fair to high enantioselectivities (46-90%). Ozonolysis of the resulting products provides access to chiral beta-hydroxy ketones, which are not readily prepared from direct asymmetric aldol reaction of acetone with ketones.     

The application of a structurally simple,recyclable, and large-scale l-prolinamide catalyst for asymmetric aldol reactions

A highly efficient, bifunctional prolinamide catalyst, which consists of chiral proline and trans-cyclohexanediamine moieties, was prepared and evaluated in the direct asymmetric aldol reactions of various ketones and aldehydes. The catalyst displayed impressive catalytic activity toward heterocyclic ketones containing oxygen, sulfur, or nitrogen, which have not been sufficiently explored. The substrate scope also covered cyclic and acyclic ketones. With heterocyclic ketones or cyclohexanone, the aldol reactions gave products in high yields and with respectable enantioselectivities (87–99% ee) and diastereoselectivities (up to >99:1 anti/syn). The catalyst could be recycled and reused up to seven times resulting in good yields and with good selectivities. This catalyst is also efficient in large-scale reactions with the enantioselectivities remaining at the same level as in the experimental scale reactions.     

Enantioselective allylation of ketones catalyzed by chiral In(III)-PYBOX complexes

In the presence of 20 mol% of chiral catalytic complex prepared from In(OTf)3 and chiral PYBOX, allyltributylstannane reacted with achiral ketones to afford the corresponding homoallylic alcohols in moderate to high enantioselectivities (54-95% ee), which constitutes the first example of enantioselective allylation of ketones catalyzed by the chiral In(III)-PYBOX complex.     

First catalytic asymmetric synthesis of beta-amino-beta-polyfluoroalkyl ketones via proline-catalysed direct asymmetric carbon-carbon bond formation reaction of polyfluoroalkylated aldimines

Proline-catalysed direct asymmetric carbon-carbon bond formation reaction of polyfluoroalkylated aldimines with acetone afforded the corresponding beta-(p-methoxyphenyl)amino-beta-polyfluoroalkyl ketones in high enantioselectivities (up to 98% ee).     

Enantioselective Reformatsky reaction of ethyl iododifluoroacetate with ketones

Two approaches have been developed for the enantioselective Reformatsky reaction of ethyl iododifluoroacetate with ketones to form a quaternary carbon centre using (1R,2S)-1-phenyl-2-(1-pyrrolidinyl)-1-propanol as the chiral ligand. Good yields and high enantioselectivities (80-91% ee) were achieved with a range of alkyl aryl ketones in a convenient one-pot protocol using ethyl iododifluoroacetate and diethylzinc to form the difluorinated Reformatsky reagent homogeneously. In the traditional two-step Reformatsky reaction using the preformed Reformatsky reagent generated from ethyl iododifluoroacetate and zinc dust, good yields and good enantioselectivities (75-84% ee) were also obtained.     

Organocatalytic and highly enantioselective direct alpha-amination of aromatic ketones

The first highly enantioselective direct alpha-amination of aryl ketones was reported to be catalyzed by organic primary amines derived from cinchona alkaloids. Excellent enantioselectivities (88-99% ee) have been achieved for a broad spectrum of aryl ketones. The presence of 4 A molecular sieves was of great assistance for the high conversions and enantiocontrol.     

The direct catalytic asymmetric alpha-aminooxylation reaction: development of stereoselective routes to 1,2-diols and 1,2-amino alcohols and density functional calculations

Proline-catalyzed direct asymmetric alpha-aminooxylation of ketones and aldehydes is described. The proline-catalyzed reactions between unmodified ketones or aldehydes and nitrosobenzene proceeded with excellent diastereo- and enantioselectivities. In all cases tested, the corresponding products were isolated with >95 % ees. Methyl alkyl ketones were regiospecifically oxidized at the methylene carbon atom to afford enantiomerically pure alpha-aminooxylated ketones. In addition, cyclic ketones could be alpha,alpha'-dioxidized with remarkably high selectivity, furnishing the corresponding diaminooxylated ketones with >99 % ees. The reaction mechanism of the proline-catalyzed direct asymmetric alpha-aminooxylation was investigated, and we performed density functional theory (DFT) calculations in order to investigate the nature of the plausible transition states further. We also screened other organocatalysts for the asymmetric alpha-oxidation reaction and found that several proline derivatives were also able to catalyze the transformation with excellent enantioselectivities. Moreover, stereoselective routes for the synthesis of monoprotected vicinal diols and hydroxyketones were found. In addition, short routes for the direct preparation of enantiomerically pure epoxides and 1,2-amino alcohols are presented. The direct catalytic alpha-oxidation is also a novel route for the stereoselective preparation of beta-adrenoreceptor antagonists.     

Highly efficient and recyclable heterogeneous asymmetric transfer hydrogenation of ketones in water

A highly efficient heterogeneous asymmetric transfer hydrogenation of ketones in water was developed for the first time, which exhibited excellent enantioselectivities, distinct acceleration effect and remarkably high recyclabilities.     

Direct L-proline-catalyzed asymmetric alpha-amination of ketones

The first direct catalytic asymmetric alpha-amination of ketones catalyzed by l-proline has been developed. The reactions proceed with various azodicarboxylates as the nitrogen source in high yields and excellent enantioselectivities (up to 99% ee). The scope and potential of the reaction are demonstrated by further transformation of the alpha-hydrazino ketones formed to both optically active syn and anti-alpha-amino alcohol derivatives.     

Synthesis of fluorine-substituted [2.2]paracyclophane-based carbene precursors for copper-catalyzed enantioselective boration of α,β-unsaturated ketones

Fluorine-substituted [2.2]paracyclophane-based carbene precursors have been successfully synthesized and applied to copper-catalyzed asymmetric β-boration of α,β-unsaturated ketones. Fluorination of the planar chiral carbenes has a beneficial impact on the catalytic performance of the relevant complexes. A variety of chiral β-boryl ketones were obtained in excellent yields (up to 99%) and with high enantioselectivities (up to 99% ee).     

Enantioselective aldol reactions of α,β-unsaturated ketones with trifluoroacetophenone catalyzed by a chiral primary amine

Chiral primary amine catalyzed direct asymmetric aldol reactions of ketones with trifluoroacetophenone, afforded trifluoromethylated β-hydroxycarbonyl aldol products bearing a quaternary carbon stereogenic center in high yields (up to 93% yield) and with high to excellent enantioselectivities of up to 99% ee.     

Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).