Highly enantioselective direct conjugate addition of ketones to nitroalkenes promoted by a chiral primary amine-thiourea catalyst

Primary amine-thiourea derivative 1 is an active and highly enantioselective catalyst for the conjugate addition of ketones to nitroalkenes. Broad substrate scope is described, with nitroalkenes bearing either aromatic or aliphatic substituents and a wide variety of ketones shown to be useful reacting partners. Ethyl ketones react preferentially, generating anti products with methyl-bearing stereocenters with good-to-excellent diastereoselectivity. An enamine mechanism is indicated, with cooperative activation of the electrophile by the thiourea and of the ketone by the primary amine.     

Conformational study of chiral cisoid enamino ketones

A study of a number of chiral cisoid cyclic enamino ketones by the circular dichroism method showed that they contain an inner disymmetric chromophore. The presence of homoconjugation of the phenyl and enamino ketone chromophores as a result of the drawing together of their orbitals in space was also established.Communication XXXVI from the series Stereochemical Studies; see [1] for communication XXXVTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 511–515, April, 1976.     

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.     

Conformational study of chiral heterocyclic enamino ketones

An assumption regarding the existence of a homoconjugation effect involving enaminoketo and phenyl groups as a result of the drawing together in space of their orbitals was made on the basis of circular dichroism (CD) data and an examination of the preferred conformations of two-ring enamino ketones with -phenylethyl and -benzylethyl substituents. A study of enamino ketones with a chiral alkyl substituent attached to the nitrogen atom made it possible to confirm this assumption.Communication XLIX from the series Stereochemical Studies. See [1] for communication XLVIII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1230–1233, September, 1978.     

Organocatalytic asymmetric direct Michael addition of aromatic ketones to alkylidenemalononitriles

The asymmetric direct Michael addition of aromatic ketones to highly active alkylidenemalononitriles was investigated by employing a chiral primary amine 9-amino-9-deoxyepicinchonine. In general modest to good enantioselectivities (71–84% ee) could be obtained in acceptable isolated yields (48–85%) for an array of substrates.     

Asymmetric allylboration of ketones catalyzed by chiral diols

Chiral BINOL-derived diols catalyze the enantioselective asymmetric allylboration of ketones. The reaction requires 15 mol % of 3,3'-Br2-BINOL as the catalyst and allyldiisopropoxyborane as the nucleophile. The reaction products are obtained in good yields (76-93%) and high enantiomeric ratios (95:5-99.5:0.5). High diastereoselectivities (dr >/= 98:2) and enantioselectivities (er >/= 98:2) are obtained in the reactions of acetophenone with crotyldiisopropoxyboranes.     

Practical ruthenium/lipase-catalyzed asymmetric transformations of ketones and enol acetates to chiral acetates

Ketones were asymmetrically transformed to chiral acetates by one-pot processes using a lipase and an achiral ruthenium complex under 1 atm of hydrogen gas in ethyl acetate. Molecular hydrogen was also effective for the transformation of enol acetates to chiral acetates without additional acyl donors with the same catalyst system.     

High-performance liquid chromatographic separation of chiral metallocenic ketones and alcohols

The enantiomers of chiral (arene)tricarbonylchromium ketones and alcohols were separated by high-performance liquid chromatography with a Chiralcel OD column. The absolute configuration of the ketones was assigned on the basis of the sign of optical rotation determined with an on-line detector.     

Theoretical elucidation on the regio-, diastereo-, and enantio-selectivities of chiral primary-tertiary diamine catalyst for asymmetric direct aldol reactions of aliphatic ketones

The asymmetric direct aldol reactions of aliphatic ketones (acetone, butanone, and cyclohexanone) with 4-nitrobenzaldehyde catalyzed by a chiral primary-tertiary diamine catalyst (trans-N,N-dimethyl diaminocyclohexane) have been investigated by performing density functional theory calculations to rationalize the experimentally observed stereoselectivities. Focused on the crucial C-C bond-forming steps, we located several low-lying transition states and predicted their relative stabilities. The calculated results demonstrate that the catalytic direct aldol reactions of acetone favors the (S)-enantiomer and that butanone prefers the branched syn-selective product, while cyclohexanone yields predominantly the opposite anti-selective product. The theoretical results are in good agreement with the experimental findings and provide a reasonable explanation for the high enantioselectivity and diastereoselectivity, as well as regioselectivity, of the aldol reactions under consideration.     

Recyclable chiral diamine-polyoxometalate (POM) acids catalyzed asymmetric direct aldol reaction of aromatic aldehydes with long-chain aliphatic ketones

In this Letter, we studied the asymmetric direct aldol reaction of long-chain aliphatic ketones with aromatic aldehydes, using chiral diamine-polyoxometalate acid combined organocatalysts. High yields (up to 90%) and enantioselectivities (up to 90% ee) were obtained under solvent-free conditions with the optimized catalyst. Furthermore, such organocatalysts could be easily recycled and reused for four times without significant loss of reactivity and enantioselectivity.     

The direct formation of ketones by reaction of methyl- and aryl-(carbonyl)(iodo)pentamethylcyclopentadienylrhodium complexes with organic iodides

[C₅Me₅Rh(aryl)(CO)I] reacts with methyl iodide to give [(C₅Me₅RhI₂)₂] and arylCOMe; similar reactions occur between [C₅Me₅Rh(Me)(CO)I] and RI to give the ketones RCOMe (R = Ph, Me, Et, or Pr).     

Direct enantioselective Michael addition of aldehydes to vinyl ketones catalyzed by chiral amines

Chiral amines such as (S)-2-[bis(3,5-dimethylphenyl)methyl]pyrrolidine and the C(2)-symmetric (2S,5S)-2,5-diphenylpyrrolidine can catalyze the direct enantioselective Michael addition of simple aldehydes to vinyl ketones. The conditions for this organocatalytic reaction have been optimized and it has been found that the chiral amines catalyze the formation of optically active substituted 5-keto aldehydes in good yields and enantioselectivities, using aldehydes and, e.g., methyl vinyl ketone as starting compounds. Taking into account that the chiral amine can activate the aldehyde and/or the enone, the mechanism for the reaction has been investigated. On the basis of intermediate synthesis, nonlinear effect, and theoretical investigations, the mechanism for the catalytic direct enantioselective Michael addition of aldehydes to vinyl ketones is discussed.     

A highly selective, organocatalytic route to chiral 1,2-oxazines from ketones

A sequential, organocatalysed asymmetric reaction to access chiral 1,2-oxazines from achiral ketone starting materials is reported, which proceeds in moderate to good yields and excellent enantioselectivity.     

Asymmetric hydrogenation of ketones with polymer-supported chiral 1,2-diphenylethylenediamine

[reaction: see text] A poly(ethylene glycol)-supported chiral diamine (PEG-2), in which the polymer is attached to the phenyl rings, has been synthesized and shown to be highly effective in asymmetric hydrogenation of unfunctionalized aromatic ketones with the possibility of reuse. PEG-2 can also serve as a chiral scaffold on which various immobilized chiral catalysts could be easily built.     

Catalytic asymmetric cyanosilylation of ketones with chiral Lewis base

The development of broadly applicable and practical catalytic approaches for the enantioselective creation of quaternary stereocenters remains a highly desirable yet challenging goal. In this Communication, we describe a highly enantioselective cyanosilylation of acetal ketones (alpha,alpha-dialkoxy ketones) catalyzed by modified cinchona alkaloids. This reaction is the first highly enantioselective cyanosilylation of ketones catalyzed by an organic chiral Lewis base and is found to be highly efficient with acetal ketones bearing a broad range of alkyl, aryl, alkenyl, and alkynyl substituents. This new catalytic asymmetric reaction, coupled with the versatility of the acetal functionality, provides a broadly useful synthetic method for chiral building blocks bearing quaternary stereocenters. Acetal ketones, readily accessible but previously unexplored in asymmetric synthesis, demonstrate unusual reactivity and selectivity toward the nucleophilic cyanosilylation, thereby suggesting that they may be interesting substrates for other catalytic enantioselective reactions.