129446-47-5

Usage

Uses

Used in Pharmaceutical Industry:
(R)-4'-(1-hydroxy-ethyl)benzoic methyl ester is used as a chiral building block for the synthesis of various pharmaceutical compounds due to its unique stereochemistry and functional groups. Its potential applications may include the development of new drugs or the enhancement of existing ones, particularly in the areas of medicinal chemistry and drug design.
Used in Chemical Industry:
(R)-4'-(1-hydroxy-ethyl)benzoic methyl ester is used as an intermediate in the synthesis of specialty chemicals, such as fragrances, dyes, and other fine chemicals. Its specific configuration and functional groups make it a valuable component in the creation of complex molecules with tailored properties for various applications.
Used in Research and Development:
(R)-4'-(1-hydroxy-ethyl)benzoic methyl ester serves as a valuable compound for research purposes, particularly in the study of stereochemistry, asymmetric synthesis, and the development of novel synthetic methods. Its unique structure and properties can provide insights into the behavior of chiral compounds and contribute to the advancement of chemical knowledge and technology.

Upstream product

• 3609-53-8 methyl 4-acetylbenzoate 
• 75-16-1 methylmagnesium bromide 
• 1571-08-0 methyl 4-formylbenzoate 
• 1076-96-6 methyl 4-vinylbenzoate 
• 84851-56-9 methyl 4-(1-hydroxy ethyl)benzoate 
• 67-56-1 methanol 
• 124-38-9 carbon dioxide 
• 5391-88-8 (S)-1-(4-bromophenyl)ethanol 
• 7364-20-7 4-ethyl-benzoic acid methyl ester 
• 99-90-1 para-bromoacetophenone 
• 201230-82-2 carbon monoxide 
• 5391-88-8 (R)-1-(4-bromophenyl)ethanol 

Downstream Products

• 1097210-66-6 C₁₁H₁₄O₅S 
• 129383-43-3 4-((R)-1-Propoxy-ethyl)-benzoic acid 4'-nonyloxy-biphenyl-4-yl ester 
• 119839-34-8 (R)-4-(1-propoxyethyl)benzoic acid 
• 925456-54-8 (R)-(4-(1-aminoethyl)phenyl)methanol 

Relevant academic research and scientific papers

Cobalt-catalyzed asymmetric hydroboration of aryl ketones with pinacolborane

The highly enantioselective cobalt-catalyzed hydroboration reaction of aryl ketones with HBpin was developed using iminopyridine oxazoline ligands. Halides, amines, ethers, sulfides, esters and amides are well tolerated under the mild reaction conditions, demonstrating its synthetic advantage. Substituted diaryl ketones could also be hydroborated with high enantioselectivity.

Novel non-metal catalyst for catalyzing asymmetric hydrogenation of ketone and alpha, beta-unsaturated ketone

The invention discloses a novel non-metal catalyst for catalyzing asymmetric hydrogenation of ketone and alpha, beta-unsaturated ketone. The preparation method of a chiral alcohol compound shown as formula IV comprises the following step of: reacting a ketone compound shown as formula V with hydrogen under the catalysis of tri(4-hydrotetrafluorophenyl)boron and a chiral oxazoline compound to obtain the chiral alcohol compound shown as the formula IV; the preparation method of a chiral tetralone compound shown as formula VI comprises the following step of: under the catalysis of tri(4-hydrotetrafluorophenyl)boron and a chiral oxazoline compound, reacting an alpha, beta-unsaturated ketone compound shown as formula VII with hydrogen to obtain the chiral tetralone compound shown as the formula VI. The method has the advantages of easy synthesis of raw materials, mild reaction conditions, simple operation, high stereoselectivity and the like, the ee value of the product is up to 92%, and the yield is up to 99%.

Highly Active Cooperative Lewis Acid—Ammonium Salt Catalyst for the Enantioselective Hydroboration of Ketones

Enantiopure secondary alcohols are fundamental high-value synthetic building blocks. One of the most attractive ways to get access to this compound class is the catalytic hydroboration. We describe a new concept for this reaction type that allowed for exceptional catalytic turnover numbers (up to 15 400), which were increased by around 1.5–3 orders of magnitude compared to the most active catalysts previously reported. In our concept an aprotic ammonium halide moiety cooperates with an oxophilic Lewis acid within the same catalyst molecule. Control experiments reveal that both catalytic centers are essential for the observed activity. Kinetic, spectroscopic and computational studies show that the hydride transfer is rate limiting and proceeds via a concerted mechanism, in which hydride at Boron is continuously displaced by iodide, reminiscent to an SN2 reaction. The catalyst, which is accessible in high yields in few steps, was found to be stable during catalysis, readily recyclable and could be reused 10 times still efficiently working.

Enantioselective direct, base-free hydrogenation of ketones by a manganese amido complex of a homochiral, unsymmetrical P-N-P′ ligand

The use of manganese in homogeneous hydrogenation catalysis has been a recent focus in the pursuit of more environmentally benign base metal catalysts. It has great promise with its unique reactivity when coupled with metal-ligand cooperation of aminophosphine pincer ligands. Here, a manganese precatalyst Mn(P-N-P′)(CO)2, where P-N-P′ is the amido form of the ligand (S,S)-PPh2CHPhCHPhNHCH2CH2PiPr2, has been synthesized and used for base-free ketone hydrogenation. This catalyst shows exceptionally high enantioselectivity and good activity, with tolerance for base-sensitive substrates. NMR structural analysis of intermediates formed by the reaction of the amido complex with hydrogen under pressure identified a reactive hydride with an NOE contact with the syn amine proton. Computational analysis of the catalytic cycle reveals that the heterolytic splitting of dihydrogen across the MnN bond in the amido complex has a low barrier while the hydride transfer to the ketone is the turnover-limiting step. The pro-S transition state is found to be usually much lower in energy than the pro-R transition state depending on the ketone structure, consistent with the high (S) enantiomeric excess in the alcohol products. The energy to reach the transition state is higher for the distortion of the in-coming ketone than that of the hydride complex. In a one-to-one comparison with the similar iron catalyst FeH2(CO)(P-NH-P′), the manganese catalyst is found to have higher enantioselectivity, often over 95% ee, while the iron catalyst has higher activity and productivity. An explanation of these differences is provided on the basis of the more deformable iron hydride complex due to the smaller hydride ligands.

Asymmetric Hydrogenation of Ketones and Enones with Chiral Lewis Base Derived Frustrated Lewis Pairs

The concept of frustrated Lewis pairs (FLPs) has been widely applied in various research areas, and metal-free hydrogenation undoubtedly belongs to the most significant and successful ones. In the past decade, great efforts have been devoted to the synthesis of chiral boron Lewis acids. In a sharp contrast, chiral Lewis base derived FLPs have rarely been disclosed for the asymmetric hydrogenation. In this work, a novel type of chiral FLP was developed by simple combination of chiral oxazoline Lewis bases with achiral boron Lewis acids, thus providing a promising new direction for the development of chiral FLPs in the future. These chiral FLPs proved to be highly effective for the asymmetric hydrogenation of ketones, enones, and chromones, giving the corresponding products in high yields with up to 95 % ee. Mechanistic studies suggest that the hydrogen transfer to simple ketones likely proceeds in a concerted manner.

Enantioselective Hydroboration of Ketones Catalyzed by Rare-Earth Metal Complexes Containing Trost Ligands

Four chiral dinuclear rare-earth metal complexes [REL1]2 (RE = Y(1), Eu(2), Nd(3), La (4)) stabilized by Trost proligand H3L1 (H3L1 = (S,S)-2,6-bis[2-(hydroxydiphenylmethyl)pyrrolidin-1-ylmethyl]-4-methylphenol) were first prepared, and all were characterized by X-ray diffraction. Complex 4 was employed as the catalyst for enantioselective hydroboration reaction of substituted ketones, and the corresponding secondary alcohols with excellent yields and high ee values were obtained using reductant HBpin. The same result was also achieved using the combination of lanthanium amides La[N(SiMe3)2]3 with Trost proligand H3L1 in a 1:1 molar ratio. The experimental findings and DFT calculation revealed the possible mechanism of the enantioselective hydroboration reaction and defined the origin of the enantioselectivity in the current system.

Asymmetric Magnesium-Catalyzed Hydroboration by Metal-Ligand Cooperative Catalysis

Asymmetric catalysis with readily available, cheap, and non-toxic alkaline earth metal catalysts represents a sustainable alternative to conventional synthesis methodologies. In this context, we describe the development of a first MgII-catalyzed enantioselective hydroboration providing the products with excellent yields and enantioselectivities. NMR spectroscopy studies and DFT calculations provide insights into the reaction mechanism and the origin of the enantioselectivity which can be explained by a metal-ligand cooperative catalysis pathway involving a non-innocent ligand.

The open d-shell enforces the active space in 3d metal catalysis: Highly enantioselective chromium(ii) pincer catalysed hydrosilylation of ketones

Bis(oxazolinyldimethylmethyl)pyrrol (PdmBox) stereodirecting ligands provided the key to the chromium(ii)-catalysed highly enantioselective hydrosilylation of ketones. A rare square planar, chiral chromium(ii) alkyl complex was found to serve as a potent precatalyst for the reduction of a broad range of aryl alkyl and dialkyl ketone derivatives. The stereoelectronic preference of the open d4 shell of chromium(ii) firmly locks the molecular catalyst in a square planar geometry giving rise to two blocked quadrants of the coordination sphere. This earth-abundant base metal catalytic platform produces the corresponding chiral alcohols in excellent isolated yields with up to 98 %ee under mild reaction conditions (-40 °C to rt) and at low catalyst loadings (as low as 0.5 mol%).

CGRP RECEPTOR ANTAGONISTS

The present invention provides a compound of Formula II: (II) or a pharmaceutically acceptable salt thereof.

P450 BM3-Catalyzed Regio- and Stereoselective Hydroxylation Aiming at the Synthesis of Phthalides and Isocoumarins

Cytochrome P450 BM3 monooxygenases are able to catalyze the regio- and stereoselective oxygenation of a broad range of substrates, with promising potential for synthetic applications. To study the suitability of P450 BM3 variants for stereoselective benzylic hydroxylation of 2-alkylated benzoic acid esters, the biotransformation of methyl 2-ethylbenzoate, resulting in both enantiomeric forms of 3-methylphthalide, was investigated. In the case of methyl 2-propylbenzoate as a substrate the regioselectivity of the reaction was shifted towards β-hydroxylation, resulting in the synthesis of enantioenriched R- and S-configured 3-methylisochroman-1-one. The potential of P450 BM3 variants for regio- and stereoselective synthesis of phthalides and isocoumarins offers a new route to a class of compounds that are valuable synthons for a variety of natural compounds.