Asymmetric Mukaiyama aldol reaction of silyl enol ethers with aldehydes using a polymer-supported chiral Lewis acid catalyst

Chiral N-sulfonylated α-amino acid monomer (5) derived from (S)-tryptophan was copolymerized with styrene and divinylbenzene under radical polymerization conditions to give a polymer-supported N-sulfonyl-(S)-tryptophan (6). Treatment of the polymer-supported chiral ligand with 3,5-bis(trifluoromethyl)phenyl boron dichloride afforded a polymeric Lewis acid catalyst (16) effective for asymmetric Mukaiyama aldol reaction of silyl enol ethers and aldehydes. Various aldehydes were allowed to react with silyl enol ethers in the presence of the polymeric chiral Lewis acid to give the corresponding aldol adducts in high yield with high levels of enantioselectivity.     

Desymmetrisation of a centrosymmetric molecule by carbon-carbon bond formation: asymmetric aldol reactions of a centrosymmetric dialdehyde

The desymmetrisation of centrosymmetric molecules by enantioselective carbon-carbon bond formation has been reported for the first time. A bimetallic zinc catalyst developed by Trost was exploited in the desymmetrisation of a centrosymmetric dialdehyde. The approach was successful with a range of ketone nucleophiles and was uniformly highly diastereoselective (>98:<2). The yield and the enantioselectivity of the reaction varied as a function of the ketone used, and the desymmetrised products were obtained in up to 74 % yield and 97 % ee (ee=enantiomeric excess). The desymmetrisation of centrosymmetric molecules by enantioselective carbon-carbon bond formation is an efficient and convergent synthetic approach which is likely to find wide application in synthesis, particularly in the total synthesis of natural products with embedded centrosymmetric fragments.     

Platinum(II) complex-catalyzed enantioselective aldol reaction with ketene silyl acetals in DMF at room temperature

[{(R)-binap}Pt(μ-OH)]₂2X is a weak Lewis acid, which can catalyze the enantioselective aldol reaction of aldehydes with ketene silyl acetals in DMF at room temperature. The platinum(II) complex-catalyzed the enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-(1-trimethylsilyloxy)propene gave the corresponding aldols in high yields with enantioselectivity up to 92%. With 5 mol % loading of the complexes, the enantioselective aldol reaction of aldehydes with 1-benzyloxy-1-(trimethylsilyloxy)propene smoothly proceeded in DMF containing 10% HMPA as to predominantly give anti-propionates with enantioselectivity up to 89%, irrespective of the silyl nucleophile geometry.     

Development of an N-sulfinyl prolinamide for the asymmetric aldol reaction

A new class of organocatalysts is reported that incorporates an N-sulfinyl amide in place of the carboxylic acid of proline to serve as a hydrogen bond donor, chiral directing group, and solubilizing element. The successful application of this type of catalyst to the asymmetric aldol reaction of acetone and aryl aldehydes, for which proline performs poorly, is also described.     

Felkin-Anh selectivity in Rh(bisoxazolinylphenyl)-catalyzed reductive aldol coupling reaction: asymmetric synthesis of stereotriads

The catalytic reductive aldol coupling of 2-phenylpropionaldehyde and acrylate derivatives with rhodium-bisoxazolinyl catalysts resulted in high Felkin-Anh selectivity (β,γ-syn) up to 98% accompanied by α,β-anti diastereoselectivity and high enantiomeric excesses up to 99%.     

Novel Cinchona alkaloid derived ammonium salts as catalysts for the asymmetric synthesis of beta-hydroxy alpha-amino acids via aldol reactions

Using the cinchonidine-derived phase-transfer catalyst developed by Park and Jew as a lead structure, we have prepared novel chiral ammonium salts and investigated their efficacy for the preparation of β-hydroxy α-amino acids via asymmetric aldol reactions. The modifications were performed at C3 of the cinchonidine nucleus and include dimers as well as catalysts possessing electron-deficient alkyne and alkene moieties. Some of the new catalysts yielded improvements relative to the Park-Jew catalyst in the aldol reaction.     

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.     

Aza variant of intramolecular nucleophile-catalyzed aldol lactonization (NCAL): formal synthesis of (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol

Aza variant of intramolecular catalytic, asymmetric nucleophile-catalyzed, aldol lactonization (NCAL) reaction has been explored to synthesize β-lactone fused nitrogen heterocycles as aza sugars’ precursors by employing achiral amino acids. The utility of these bicyclic β-lactones is presented by the formal synthesis of aza sugars, (3S,4R) and (3R,4S) 4-(hydroxymethyl)pyrrolidin-3-ol.     

Organocatalytic asymmetric aza-Michael reaction: enantioselective addition of O-benzylhydroxylamine to chalcones

A novel organocatalytic approach for aza-Michael reaction of chalcones using commercial and non-expensive O-benzylhydroxylamine and a readily available organocatalyst is provided. The use of this simple protocol results in β-keto hydroxylamines in up to 60% ee, thus extending the generality of the catalytic enantioselective aza-Michael reaction.     

Expeditious asymmetric synthesis of a stereoheptad corresponding to the C(19)-C(27)-ansa chain of rifamycins: formal total synthesis of Rifamycin S

In the presence of sulfur dioxide and an acid promoter, (-)-(1E,3Z)-2-methyl-1-((1S)-1-phenylethoxy)penta-1,3-dien-3-yl isobutyrate reacts with (Z)-3-(trimethylsilyloxy)pent-2-ene giving a silyl sulfinate intermediate that undergoes, in the presence of palladium catalyst, a desilylation and retro-ene elimination of SO(2) with formation of (-)-(1Z,2S,3R,4S)-1-ethylidene-2,4-dimethyl-5-oxo-3-((1S)-1-phenylethoxy)-heptyl isobutyrate as major product. This ethyl ketone undergoes cross-aldol reaction with (2S)-2-methyl-3-[(tert-butyldimethylsilyl)oxy]propanal giving an aldol that is reduced into a stereoheptad corresponding to the C(19)-C(27)-segment of Rifamycins with high diastereoselectivity and enantiomeric excess.     

A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand as an efficient catalyst for the Heck reaction of aryl bromides with styrene. The effect of the amino group

A palladium complex with a new hemilabile amino- and sulfur-containing phosphinite ligand has been synthesised and its crystal structure determined. This system efficiently catalyses the Heck reaction of aryl bromides with styrene at 130°C after 24 h, with turnover numbers of up to 100000 and with a selectivity towards trans-stilbenes ranging from 91.5 to 96.3%. The analogous sulfur-containing phosphinite without the amino group has also been synthesised and subjected to the Heck reaction. The constructive role of the amino group on the formation of the P,S-chelate palladium complex as well as in the Heck reaction is discussed.     

Practical and efficient entry to isoflavones by Pd(0)/C-mediated Suzuki-Miyaura reaction. Total synthesis of geranylated isoflavones

A scalable synthesis of isoflavones taking advantage of the Suzuki-Miyaura reaction catalyzed by Pd(0)/C is described. The approach developed has been extended to the total synthesis of 7-O-geranylformononetin, griffonianone D, and conrauinone D, which did not display cytotoxicity against human HeLa carcinoma cells. In addition, this study established unambiguously the absolute configuration of natural griffonianone D.     

Synthesis and characterization of high cis-polybutadiene: influence of monomer concentration and reaction temperature

This paper reports the study of the dependence of reaction conversion, catalyst activity, polymer microstructure, molecular weight, molecular weight distribution curves and Mooney viscosity on reaction temperature and monomer concentration in the reaction medium used in the synthesis of high cis-polybutadiene. A ternary catalyst system composed by neodymium versatate, trans-butyl chloride and diisobutylaluminum hydride was used in its synthesis. The highest molecular weights were obtained at polymerization temperatures in the range from 70 to 80 °C. The highest content of cis-1,4 repeating units (about 99%) was observed when the polymerization was carried out at the lowest initial monomer concentration (0.56 mol/l).     

Synthesis of a new chiral organocatalyst derived from (S)-proline containing a 1,2,4-triazolyl moiety and its application in the asymmetric aldol reaction. Importance of one molecule of water generated in situ

A simple and efficient preparation of a novel chiral derivative of (S)-proline containing a 1,2,4-triazolyl moiety is described. The high-yielding synthetic protocol includes the use of microwave irradiation to afford new chiral pyrrolidine derivatives in high yield. Our triazolyl-containing heterocycle was evaluated as organocatalyst (10 mol% load, under neat reaction conditions) in the enantioselective aldol reaction between four different types of ketones and a variety of aryl aldehydes. Good results in terms of enantioselectivity and chemical yield were observed under solvent-free reaction conditions and in the absence of any additive. Evidence is provided for the involvement of the water molecule generated upon enamine formation in the transition state of the aldol reaction.     

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by Ti(IV) complexes of C2-symmetrical chiral BINOL derivatives

Enantioselective addition of diethylzinc to a series of aromatic aldehydes is developed using new chiral C₂-symmetric ligand (S)-2,2′-(1,1′-binaphthyl-2,2′-diylbis(oxy))bis(methylene)bis(4-nitrophenol) (S)-2b. The catalytic system employing 10 mol % of (S)-2b and 120 mol % of Ti(OiPr)₄ was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes with electron-donating and electron-withdrawing substituents, giving up to 89% ee and up to 95% yield of the corresponding secondary alcohol under mild conditions.     

Stereoselective 1,5-rearrangement of vinylketene-N,O-acetals: novel vinylogous Ferrier reaction

Vinylketene-N,O-acetals underwent Lewis acid-induced 1,3- or 1,5-rearrangement to afford the corresponding C-alkylated products. 1,5-Rearrangement proceeded predominantly in dichloromethane, and it is quite interesting to achieve an unprecedented high degree of asymmetric induction in such a remote position. Crossover experiments indicated that the reaction proceeded through an ion pair intermediate.     

Noncovalent anchoring of asymmetric hydrogenation catalysts on a new mesoporous aluminosilicate: application and solvent effects

A new Brønsted acidic aluminosilicate, AlTUD‐1, with ideal characteristics for catalyst immobilisation (mesoporous structure, high surface area, and high Al_tetrahedral/Si ratio), was used successfully for the noncovalent anchoring of two well‐established asymmetric hydrogenation catalysts: [Rh^I(cod){(R,R)‐MeDuPHOS}]BF₄ ( 1 ) and [Rh^I(cod){(S,S)‐DiPAMP}]BF₄ ( 2 ). The new heterogeneous catalysts, 1 ‐AlTUD‐1 and 2 ‐AlTUD‐1, prepared by a straightforward ion‐exchange procedure, were highly active and selective in the asymmetric reduction of dimethyl itaconate ( 3 ) and methyl 2‐acetamidoacrylate ( 4 ), giving enantiomeric excesses of up to >98 %. The catalysts showed similar behaviour to their homogeneous counterparts. Catalyst 2 ‐AlTUD‐1 could be re‐used multiple times without loss of enantioselectivity or activity. Leaching of Rh showed a significant dependence on the polarity of the solvent in which the catalysis was performed. By applying tert‐butylmethyl ether (MTBE) as solvent, the loss of Rh could be reduced to <0.1 %. The solvent also had a noteworthy effect on the enantioselectivity in the hydrogenation of 4 (an effect not seen with 3 as substrate), that is, in MeOH the ee was 92 %, in MTBE it dropped to 26 % when using 2 ‐AlTUD‐1 as catalyst.