Chiral phosphine oxide BINAPO as a catalyst for enantioselective allylation of aldehydes with allyltrichlorosilanes

The effectiveness of chiral phosphine oxide BINAPO as a catalyst for the enantioselective addition of allyltrichlorosilanes to aldehydes was demonstrated, wherein the combination of diisopropylethylamine and tetrabutylammonium iodide as additives is crucial for accelerating the catalytic cycle.     

Chiral copper-Schiff base catalyst for asymmetric henry reaction

Five copper-Schiff base complexes were synthesized conveniently from copper(II) acetate monohydrate, salicylaldehydes, and amino alcohols. The complexes were shown to be effective as catalysts in the asymmetric Henry reaction affording nitro alkanols in up to 98% yield with moderate and good enantiomeric excess (up to ee 38.6%). Published in Russian in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 12, pp. 1754–1755. The text was submitted by the authors in English.     

Chiral Phebox-rhodium complexes as catalysts for asymmetric direct aldol reaction

Chiral bis(oxazolinyl)phenyl-rhodium complexes act as catalysts in the combination of AgOTf for direct aldol reaction of ketones and aromatic aldehydes to give the corresponding β-hydroxyketones in high anti-selectivity and a good to high enantioselectivity up to 91% ee.     

Chiral phosphine Lewis base catalyzed asymmetric aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone and phenyl acrylate

In the aza-Baylis-Hillman reaction of N-sulfonated imines with methyl vinyl ketone (MVK) promoted by chiral phosphine Lewis base: (R)-2'-diphenylphosphanyl-[1,1']binaphthalenyl-2-ol (10 mol%), the aza-Baylis-Hillman adducts 1 were obtained in good yields with high ee (70-94% ee) at -30 degrees C in THF. In CH2Cl2 upon heating at 40 degrees C, the aza-Baylis-Hillman reaction of N-sulfonated imines with phenyl acrylate gave the adducts 2 in high yields (60-97%) with moderate ee (52-77%).     

Lewis base catalyzed aldol additions of chiral trichlorosilyl enolates and silyl enol ethers

[structures: see text] The consequences of double diastereodifferentiation in chiral Lewis base catalyzed aldol additions using chiral enoxysilanes derived from lactate, 3-hydroxyisobutyrate, and 3-hydroxybutyrate have been investigated. Trichlorosilyl enolates derived from the chiral methyl and ethyl ketones were subjected to aldolization in the presence of phosphoramides, and the intrinsic selectivity of these enolates and the external stereoinduction from chiral catalyst were studied. In the reactions with the lactate derived enolate, the strong internal stereoinduction dominated the stereochemical outcome of the aldol addition. For the 3-hydroxyisobutyrate- and 3-hydroxybutyrate derived enolates, the catalyst-controlled diastereoselectivities were observed, and the resident stereogenic centers exerted marginal influence. The corresponding trimethylsilyl enol ethers were employed in SiCl4/bisphosphoramide catalyzed aldol additions, and the effect of double diastereodifferentiation was also investigated. The overall diastereoselection of the process was again controlled by the strong external influence of the catalyst.     

Lewis base-promoted aldol reaction of dimethylsilyl enolates in aqueous dimethylformamide: use of calcium chloride as a Lewis base catalyst.

In the presence of CaCl2, dimethylsilyl (DMS) enolates smoothly reacted with aldehydes under mild conditions to give aldol adducts in good to high yields. The catalytic activities of various metal and tetrabutylammonium salts have revealed that CaCl2 works as a Lewis base catalyst to activate DMS enolates. The CaCl2-promoted reaction proceeded even in the presence of water or in pure water. This catalytic system was applicable to the aldol reaction with aqueous aldehydes such as formalin.     

Practical aldol reaction of trimethylsilyl enolate with aldehyde catalyzed by N-methylimidazole as a Lewis base catalyst

Aldol reaction of trimethylsilyl enolate with aldehyde proceeded in the presence of a catalytic amount of a Lewis base, N-methylimidazole, and lithium chloride in DMF at room temperature. Not only aryl aldehyde but also alkyl aldehyde provided the aldol product in satisfactory yields. The reaction was mild enough to apply to the aldehyde having HO, AcO, THPO, TBDMSO, MeS, pyridyl or olefinic group. Microwave irradiation accelerated the reaction.     

Ionic liquid-supported proline as catalyst in direct asymmetric aldol reaction

Ionic-liquid-supported proline derivative was synthesized starting from L-proline and was used to catalyze direct asymmetric aldol reaction of acetone with aldehydes. The yield and optical purity of the condensation products, the corresponding β-hydroxy carbonyl compounds were comparable with those obtained under homogeneous conditions. Moreover, the catalyst can be reused for at least four times. Published in Russian in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 12, pp. 1834–1837. The text was submitted by the authors in English.     

Lewis base catalyzed, enantioselective aldol addition of methyl trichlorosilyl ketene acetal to ketones

The catalytic enantioselective addition of an acetate enolate equivalent to ketones is described. Methyl trichlorosilyl ketene acetal reacts with a wide range of ketones in the presence of pyridine N-oxide to afford the aldol addition products in excellent yields. Chiral 2,2'-pyridyl bis-N-oxides bearing various substituents at the 3,3'- and 6,6'-positions also provide excellent yields of the aldol products with variable enantioselectivities ranging from 94/6 er for aromatic ketones to nearly racemic for aliphatic ketones. An X-ray crystal structure of the complex between a catalyst and silicon tetrachloride (((P)-(R,R)-19.SiCl(4))) has been obtained. Extensive computational analysis provides a stereochemical rationale for the observed trends in enantioselectivities.     

Chiral ammonium betaines: a bifunctional organic base catalyst for asymmetric Mannich-type reaction of alpha-nitrocarboxylates

A chiral ammonium betaine, an intramolecular ion-pairing quaternary ammonium aryloxide 3, has been designed and its vast potential as an enantioselective organic base catalyst has been successfully demonstrated in the highly enantioselective direct Mannich-type reaction of alpha-substituted alpha-nitrocarboxylates 2 with various N-Boc imines 1. The present study provides a conceptually new approach toward the design of bifunctional, chiral quaternary ammonium salts and their utilizations as a homogeneous organic molecular catalyst.     

The effects of a remote stereogenic center in the Lewis base catalyzed aldol additions of chiral trichlorosilyl enolates

Chiral trichlorosilyl enolates bearing a remote stereogenic center were employed in the phosphoramide-catalyzed aldol reaction. The additions of the methyl ketone enolates proceeded with only moderate diastereoselectivities. The addition of the Z-enolate to various aldehydes selectively produced the syn relative diastereomers. In both cases, the effect of the beta-silyloxy stereogenic center was modest, and the internal diastereoselection was mainly controlled by the catalyst. [reaction: see text]     

A catalytic asymmetric strecker-type reaction promoted by Lewis acid-Lewis base bifunctional catalyst

A general asymmetric Strecker-type reaction is reported, catalyzed by the Lewis acid-Lewis base bifunctional catalyst 1. The reaction of trimethylsilyl cyanide (TMSCN) with various fluorenyl imines, including n-aldimines and alpha,beta-unsaturated imines, proceeds with good to excellent enantioselectivities in the presence of a catalytic amount of phenol as additive (20 mol%) (catalytic system 1). The products were successfully converted to the corresponding amino acid derivatives in high yields without loss of enantiomeric purity. Furthermore, hydrogenation or dihydroxylation of the products from alpha,beta-unsaturated imines afforded saturated or functionalized aminonitriles also without loss of enantiomeric purity. The absolute configuration of the products and a control experiment using catalyst 2 supported the proposed dual activation of the imine and TMSCN by the Lewis acid (Al) and the Lewis base moiety (phosphine oxide) of 1. From the mechanistic studies including kinetic and NMR experiments of the catalytic species, the role of PhOH seems to be a proton source to protonate the anionic nitrogen of the intermediate. Specifically, we have found that TMSCN is more reactive than HCN in this catalytic system, probably due to the activation ability of the phosphine oxide moiety of 1 toward TMSCN. This fact prompted us to develop the novel catalytic system 2, consisting of 1 (9 mol%), TMSCN (20 mol%) and HCN (1.2 mol eq). This new system afforded comparable results with obtained by system 1 (1 (9 mol%)-TMSCN (2 mol eq)-PhOH (20 mol%)).     

Protonated N'-benzyl-N'-prolyl proline hydrazide as highly enantioselective catalyst for direct asymmetric aldol reaction

Protonated N'-benzyl-N'-l-prolyl-l-proline hydrazide has been developed as a highly enantioselective catalyst for the asymmetric direct aldol reaction of aromatic aldehydes with ketones.     

Chiral phosphine-free Pd-mediated asymmetric allylation of prochiral enolate with a chiral phase-transfer catalyst

[reaction: see text]. A chiral phase-transfer catalyst has been applied to the asymmetric allylation of the tert-butyl glycinate-benzophenone Schiff base with various allylic acetates for the first time to give the allylated products in good yields and with comparable to higher enantioselectivity than for asymmetric alkylation at the same temperature (91-96% ee) without any chiral ligands for coordinating to the palladium.     

Trichlorosilyl triflate for enantioselective direct-type aldol reaction with chiral phosphine oxide

Trichlorosilyl triflate, in the presence of a chiral Lewis base catalyst, provides an effective method for the enantioselective direct-type aldol reaction of aldehydes and ketones. A chiral Lewis base induces both the production and activation of trichlorosilyl enol ether, yielding an aldol product in good yield and with high diastereo- and enantioselectivities.     

Regioselectivity-reversed asymmetric aldol reaction of 1,3-dicarbonyl compounds

Reverse regioselectivity: The first catalytic asymmetric C-1 functionalization of 1,3-dicarbonyl compounds by an aldol reaction is described, which regioselectively affords 6-hydroxyhexane-2,4-dione derivatives as the only product with high optical purity of up to 93?%?ee. Furthermore, this method provides a facile access to enantioenriched oxygen-containing spirooxindoles and spirobutyrolactones from simple commercial available starting materials.     

Enantioselective aldol reaction of silyl ketene acetals promoted by a Lewis base-activated Lewis acid catalyst

The enantioselective aldol reaction of a silyl ketene acetal was promoted by chiral phosphine oxide-activated tetrachlorosilane to afford the corresponding adduct in high yield with moderate enantioselectivity.     

Development of chiral dinitrones as modular Lewis base catalysts: asymmetric allylation of aldehydes with allyltrichlorosilanes

Chiral dinitrones were synthesized by the condensation of a C₂-symmetrical chiral dihydroxylamine with various aldehydes. The electronic and steric properties of the dinitrones can be modified by changing the aldehyde component. The activity of dinitrones as Lewis base catalysts was examined for the asymmetric allylation of aldehydes with allyltrichlorosilanes. Using DMPU as an additive in chloroform, the reaction proceeded at room temperature to afford allylated products in good yields and good enantioselectivities.     

Chiral 1,2-diaminocyclohexane as organocatalyst for enantioselective aldol reaction

A simple and commercially available chiral 1,2-diaminocyclohexane as catalyst, hexanedioic acid as co-catalyst could efficiently catalyze the asymmetric aldol reaction in MeOH-H₂O. Cyclic ketones as aldol substrates gave the anti-β-hydroxyketone products with moderate to good yields, diastereoselectivity and enantioselectivity (up to 78% yield, >20:1 anti/syn, 94% ee). Hydroxyacetone as aldol substrate afforded the syn-α, β-dihydroxyketones as major products in up to 85% yield with good enantioselectivity (up to >20:1 syn/anti, 93% ee).     

Synthesis of a biphenyl-based axially chiral amino acid as a highly efficient catalyst for the direct asymmetric aldol reaction

A biphenyl-based axially chiral amino acid (S)-2 has been designed and synthesized. The new amino acid (S)-2 has been found to be a more efficient catalyst than (S)-1 in the direct asymmetric aldol reaction of acetone with aldehydes. For instance, the use of only 0.1 mol % of (S)-2 was sufficient to complete the reaction between acetone and 4-nitrobenzaldehyde, giving the corresponding aldol adduct in good yield with an excellent enantioselectivity.