Rhodium-Catalyzed Asymmetric Arylation-Induced Glycolate Aldol Additions of Silyl Glyoxylates

(Diene)Rh(I) complexes catalyze the stereoselective three-component coupling of silyl glyoxylates, arylboronic acids, and aldehydes to give glycolate aldol products. The participation of Rh-alkoxides in the requisite Brook rearrangement was established through two component Rh-catalyzed couplings of silyl glyoxylates with ArB(OH)₂ to give silyl-protected mandelate derivatives. The intermediacy of a chiral Rh-enolate was inferred through enantioselective protonation using a chiral Rh-catalyst. Diastereoselective three-component couplings with aldehydes as terminating electrophiles to give racemic products were best achieved with a bulky aryl ester on the silyl glyoxylate reagent. Optimal enantioselective couplings were carried out with the tert-butyl ester variant using an anisole-derived enantiopure tricyclo[3.2.2.0^2,4]nonadiene ligand.     

Novel Polycarbonate Copolymer as Organocatalyst for Aldol and Michael Reaction

A new polymeric organocatalyst is prepared by free radical copolymerization of allyl diglycol carbonate (ADC) and Boc-protected allyl prolinate and evaluated as a chiral catalyst for aldol and Michael reaction.     

Surface-Mediated Solid Phase Reaction. IX. A Convenient Procedure for Aldol Reaction of Ketene Silyl Acetals with Aldehydes on the Solid Surface of Alumina

The aldol reaction of ketene silyl acetals with aldehydes proceeds efficiently on the solid surface of alumina impregnated with anhydrous zinc chloride under sonication providing aldol products in high yields and with good stereoselectivity.     

The Catalytic Asymmetric Aldol Reaction

The construction of C-C bonds with complete control of the stereochemical course of a reaction is of utmost importance for organic synthesis. The aldol reaction-the simple addition of an enolate donor to a carbonyl acceptor-is one of the most powerful reactions available to the synthetic chemist. In general, control of the relative and absolute configuration of the newly formed stereogenic centers has been achieved through the use of chiral starting materials or chiral auxiliaries. In recent years the search for catalytic methods that efficiently and effectively transfer chirality information has become a major effort in synthetic organic chemistry. Two different approaches have been taken toward the catalytic asymmetric aldol reaction: biocatalysis and catalysis with small molecules. Both approaches have specific advantages and limitations, and as a result are complementary to each other. The important efforts toward both approaches are reviewed in this article.     

Chiral Diamine-catalyzed Asymmetric Aldol Reaction

A highly efficient catalytic system composed of a simple and commercially available chiral primary diamine (1R,2R)-cyclohexane-1,2-diamine(6) and trifluoroacetic acid (TFA) was employed for asymmetric Aldol reaction in em-PrOH at room temperature. A loading of 10%(molar fraction) catalyst 6 with TFA as a cocatalyst could catalyze the Aldol reactions of various ketones or aldehydes with a series of aromatic aldehydes, furnishing Aldol pro- ducts in moderate to high yields(up to >99%) with enantioselectivities of up to >99% and diastereoselectivities of up to 99:1.     

Magnesium Chloride Directed Aldol and Bromination of 2-Acetylfuran

Reaction of 2-acetylfuran with diisopropylethylamine and magnesium chloride followed by bromination gave 1,3-difuryl-3-hydroxy-1-butanone and 1,3-difuryl-4-bromo-3-hydroxy-1-butanone. Under similiar conditions 2-acetythiophene failed to react.     

Migration Reaction of a Silyl Group from a Phosphorus to a Carbonyl Oxygen in a Molybdenum Coordination Sphere

The reaction of Cp anion, [C 5 H 4 CH 2 CH 2 P(TMS)Mes] m with (CH 3 CN) 3 Mo(CO) 3 leads to the formation of [( m 5 --C 5 H 4 CH 2 CH 2 --P(TMS)Mes)Mo(CO) 3 ] m , which then reacts with MeI to give a metallaphosphacyclopropane complex with silyl migration.     

Proton Migration in Benzene Complexes of Methyl and Silyl Cations

Quantum-chemical calculations at the B3LYP/6-31G(d,p) level of theory were used to optimize stationary points in the C₆H₆ + H₃X⁺ (X = C, Si) systems. At X = Si, the adduct of the cation with benzene is the most stable isomer, whereas at X = C, the para isomer is more stable than the adduct (ipso isomer). This difference is explained in terms of charge distribution in the benzene ring in toluene and phenylsilane: In the latter, the negative charge on the carbon atom attached to silicon is much higher than on the other carbon atoms, unlike toluene in which the highest negative charge is on the carbon atom para to the methyl group. Proton migration from the ipso to para position requires the lowest (X = C) and highest (X = Si) barriers to be overcome compared with the other barriers to proton migration over the benzene ring. These barriers and relative stabilities of the isomers correlate well with the charge distribution on benzene carbon atoms in toluene and phenylsilane.     

Lewis Base Catalysis of the Mukaiyama Directed Aldol Reaction: 40 Years of Inspiration and Advances

Since the landmark publications of the first directed aldol addition reaction in 1973, the site, diastereo‐, and enantioselective aldol reaction has been elevated to the rarefied status of being both a named and a strategy‐level reaction (the Mukaiyama directed aldol reaction). The importance of this reaction in the stereoselective synthesis of untold numbers of organic compounds, both natural and unnatural, cannot be overstated. However, its impact on the field extends beyond the impressive applications in synthesis. The directed aldol reaction has served as a fertile proving ground for new concepts and new methods for stereocontrol and catalysis. This Minireview provides a case history of how the challenges of merging site selectivity, diastereoselectivity, enantioselectivity, and catalysis into a unified reaction manifold stimulated the development of Lewis base catalyzed aldol addition reactions. The evolution of this process is chronicled from the authors’ laboratories as well as in those of Professor Teruaki Mukaiyama.     

Complete Switch of Reaction Specificity of an Aldolase by Directed Evolution In Vitro: Synthesis of Generic Aliphatic Aldol Products

A structure‐guided engineering of fructose‐6‐phosphate aldolase was performed to expand its substrate promiscuity toward aliphatic nucleophiles, that is, unsubstituted alkanones and alkanals. A “smart” combinatorial library was created targeting residues D6, T26, and N28, which form a binding pocket around the nucleophilic carbon atom. Double‐selectivity screening was executed by high‐performance TLC that allowed simultaneous determination of total activity as well as a preference for acetone versus propanal as competing nucleophiles. D6 turned out to be the key residue that enabled activity with non‐hydroxylated nucleophiles. Altogether 25 single‐ and double‐site variants (D6X and D6X/T26X) were discovered that show useful synthetic activity and a varying preference for ketone or aldehyde as the aldol nucleophiles. Remarkably, all of the novel variants had completely lost their native activity for cleavage of fructose 6‐phosphate.     

A Designed Amide as an Aldol Donor in the Direct Catalytic Asymmetric Aldol Reaction

The direct catalytic asymmetric aldol reaction offers efficient access to β‐hydroxy carbonyl entities. Described is a robust direct catalytic asymmetric aldol reaction of α‐sulfanyl 7‐azaindolinylamide, thus affording both aromatic and aliphatic β‐hydroxy amides with high ee values. The design of this transformation features a cooperative interplay of a soft and a hard Lewis acid, which together facilitate the challenging chemoselective enolization by a hard Brønsted base.     

区域选择性Michael/Aldol串联反应合成新型1′-茚醇拼接3-氧化吲哚类化合物

以3-烯烃氧化吲哚为起始原料,甲苯为溶剂,与丙二腈或腈基乙酸乙酯发生区域选择性Michael/Aldol串联反应,合成了6个新型的1′-茚醇拼接3-氧化吲哚类化合物,收率73%~90%, dr高达10/1,其结构经¹H NMR, ¹³C NMR和HR-MS（ESI-TOF）表征。     

Role of Additives in Chiral Amine-Catalyzed Direct Aldol Reaction

A systematic study of chiral adducts derived from amines as catalysts for aldol reaction revealed that enantioselective outcome depends on the chiral enamine intermediate and not the face-selective activation of aldehyde. A simple addition compound of proline and 8-hydroxy quinoline was found to be a good catalyst.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Small Organic Molecules for Direct Aldol Reaction

Since the pioneering finding by List and Barbas III and their coworkers that L-proline could work as a catalyst in the intermolecular direct aldol reaction, the concept of small organic molecules as catalysts has received great attention. However, new organic molecule which have better catalysis ability are reported scarcely. Our groups1 found L-Prolinamides 1 to be active catalysts for the direct aldol reaction of 4-nitrobenaldehyde with neat acetone at room temperature. The enantioselecti…     

脲衍生物有机催化靛红与乙酰乙酸酯的不对称Aldol反应

将Takemoto(硫)脲衍生物用于催化靛红与乙酰乙酸酯的不对称羟醛反应(Aldol).在0.1 mmol底物用量条件下,筛选出最佳催化剂体系为:5%(摩尔分数)催化剂N-[3, 5-双(三氟甲基)苯基]-N′-[(1S, 2S)-2-(二甲氨基)环己基]脲1b, 1 mL甲基叔丁基醚为溶剂, 0℃条件下反应.以76%～87%的产率和最高达87%的对映选择性获得了手性δ-(2-羟基吲哚-3基)-δ-羟基-β-酮酸酯.