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Usage

Uses

Used in Pharmaceutical Industry:
(S)-4-bromophenyl(phenyl)methanol is used as a building block for the synthesis of various pharmaceuticals. Its chiral nature allows for the creation of enantiomerically pure compounds, which are essential in the development of drugs with specific therapeutic effects and reduced side effects.
Used in Agrochemical Industry:
In the agrochemical industry, (S)-4-bromophenyl(phenyl)methanol is utilized as a starting material for the preparation of chiral pesticides and other agrochemicals. Its unique stereochemistry enables the development of more effective and targeted products with reduced environmental impact.
Used in Fine Chemicals Industry:
(S)-4-bromophenyl(phenyl)methanol is employed as a key intermediate in the synthesis of various fine chemicals, including fragrances, dyes, and specialty chemicals. Its versatility and chirality make it a valuable component in the production of high-quality and enantiomerically pure products.
Used as a Chiral Auxiliary:
(S)-4-bromophenyl(phenyl)methanol is used as a chiral auxiliary in asymmetric synthesis. Its (S)-stereoisomer provides a unique platform for the development of novel enantioselective reactions, leading to the production of chiral compounds with high enantiomeric purity.
Used as a Ligand in Catalysis:
(S)-4-bromophenyl(phenyl)methanol also serves as a ligand in catalytic processes, enhancing the selectivity and efficiency of various chemical reactions. Its chiral nature allows for the creation of catalysts that can selectively produce desired enantiomers, which is crucial in the synthesis of optically active compounds.
Used in Antimicrobial Applications:
(S)-4-bromophenyl(phenyl)methanol has demonstrated promising antibacterial and antifungal activities, making it a potential candidate for the development of new antimicrobial agents. Its ability to inhibit the growth of various pathogens could lead to the creation of novel treatments for bacterial and fungal infections.

Upstream product

• 29334-16-5 phenyl(4-bromophenyl)methanol 
• 101402-02-2 (S)-(4-aminophenyl)(phenyl)methanol 
• 1078-58-6 diphenylzinc 
• 1122-91-4 4-bromo-benzaldehyde 
• 5467-74-3 4-Bromophenylboronic acid 
• 100-52-7 benzaldehyde 
• 3262-89-3 triphenylboroxine 
• 1013121-08-8 (S)-(4-bromophenyl)-[cyclohexa-2,5-dien-1-yl]methanol 
• 100-58-3 phenylmagnesium bromide 
• 90-90-4 (4-bromophenyl)(phenyl)methanone 
• 841-76-9 triphenylaluminium 
• 108-86-1 bromobenzene 
• 16635-23-7 phenyltriisopropoxytitanium(IV) 
• 98-80-6 phenylboronic acid 

Downstream Products

• 1426442-20-7 C₂₁H₁₈O₃ 
• 1426442-19-4 C₁₇H₁₄O₂ 
• 1426442-43-4 C₃₀H₂₅NO₂ 
• 1426442-42-3 C₂₆H₂₁NO 
• 1426442-18-3 C₂₆H₂₆O₄ 
• 1426442-17-2 C₂₂H₂₂O₃ 

Relevant academic research and scientific papers

Bio-inspired asymmetric aldehyde arylations catalyzed by rhodium-cyclodextrin self-inclusion complexes

Transition-metal catalysts are powerful tools for carbon-carbon bond-forming reactions that are difficult to achieve using native enzymes. Enzymes that exhibit inherent selectivities and reactivities through host-guest interactions have inspired widesprea

Binaphthyl-prolinol chiral ligands: Design and their application in enantioselective arylation of aromatic aldehydes

Binaphthyl-prolinol ligands were designed and applied in enantioselective arylation of aromatic aldehydes and sequential arylation-lactonization of methyl 2-formylbenzoate. Under optimized conditions, the reactions provided the desired diarylmethanols and 3-aryl phthalides in up to 96% yields with up to 99% ee and up to 89% yields with up to 99% ee, respectively. In particular, essentially optically pure 3-aryl phthalides (over 99% ee) were obtained in large quantities through recrystallization. This journal is

Electronic Effect-Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols

Herein, we developed an electronic effect-guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl)methanols. Compared to W104A mutant previously reported with reversed S-stereoselectivity toward sec-alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of S-enantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S-(4-chlorophenyl)(pyridin-2-yl) methanol (S-CPMA), the intermediate of bepotastine, were obtained in good yields and ee values. (Figure presented.).

Molecular switch manipulating Prelog priority of an alcohol dehydrogenase toward bulky-bulky ketones

Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of unconserved residues at 214 and 237 in small and large substrate binding pockets were proven to be vital in governing the stereoselectivity. The ee values of E214Y/S237A and E214C/S237 G toward (4-chlorophenyl)-(pyridin-2-yl)-methanone were 99.3% (R) and 78.8% (S) respectively. Substrate specificity analysis revealed that similar patterns were also found with (4’-chlorophenyl)-phenylmethanone, (4’-bromophenyl)-phenylmethanone and (4’-nitrophenyl)-phenylmethanone. This study provides valuable evidence for understanding the molecular mechanism on enantioselective recognition of prochiral ketones by alcohol dehydrogenase.

Isosterically designed chiral catalysts: Rationale, optimization and their application in enantioselective nucleophilic addition to aldehydes

Proline-based N,N′-dioxide ligands were designed on the basis of isosteric approach, and were successfully applied in enantioselective nucleophilic addition to aldehydes. In the presence of 10 mol% of chiral ligand 1b, enantioselective addition of diethylzinc to aldehydes provided the corresponding secondary alcohols in up to 90% isolated yield and up to 99% ee. Similarly, using 3e as chiral ligand, enantioselective arylation and alkynylation of aldehydes also proceeded readily, leading to the desired chiral alcohols in up to 92% isolated yield at 99% ee and 80% isolated yields and up to 84% ee, respectively. The current work would shed light on expanding the structure diversity in the design of chiral ligands and chiral catalysts.

Asymmetric Hydrophosphination of Heterobicyclic Alkenes: Facile Access to Phosphine Ligands for Asymmetric Catalysis

Asymmetric hydrophosphination is the most atomically economical and straightforward approach to the construction of chiral organophosphorus compounds. Good stereoselectivities have been achieved in asymmetric hydrophosphination of an electron-deficient C=

Substituent Position-Controlled Stereoselectivity in Enzymatic Reduction of Diaryl- and Aryl(heteroaryl)methanones

We report here the discovery of a novel ketoreductase (KRED), named KmCR2, with a broad substrate spectrum on bioreduction of sterically bulky diaryl- and aryl(heteroaryl)methanones. The position of the substituent on aromatic rings (meta versus para or ortho) was revealed to control the stereospecificity of KmCR2. The stereoselective preparation of both enantiomers of diaryl- or aryl(heteroaryl)methanols using strategically engineered substrates with a traceless directing group (bromo group) showcased the potential application of this substrate-controlled bioreduction reaction. The combined use of substrate engineering and protein engineering, was demonstrated to be a useful strategy in efficiently improving stereoselectivity or switching stereopreference of enzymatic processes. (Figure presented.).

Hydroclassified Combinatorial Saturation Mutagenesis: Reshaping Substrate Binding Pockets of KpADH for Enantioselective Reduction of Bulky-Bulky Ketones

A hydroclassified combinatorial saturation mutagenesis (HCSM) strategy was proposed for reshaping the substrate binding pocket by dividing 20 amino acids into four groups based on their hydrophobicity and size. These smart HCSM libraries could significantly reduce screening effort especially for the simultaneous mutagenesis of three or more residues and lacking high throughput screening methods. Employing HCSM strategy, the stereoselectivity of KpADH, an alcohol dehydrogenase from Kluyveromyces polysporus, was efficiently improved to 99.4% ee. (4-Chlorophenyl)(pyridin-2-yl)methanone (CPMK), generally regarded as a "hard-to-reduce" ketone, was used as a model substrate, and its corresponding chiral alcohol products could be utilized as antihistamine precursors. The best variant 50C10 displayed higher binding affinity and catalytic efficiency toward CPMK with KM/kcat of 59.3 s-1·mM-1, 3.51-fold that of KpADH. Based on MD simulations, increased difference between two binding pockets, enhanced hydrophobicity, and π-π and halogen-alkyl interactions were proposed to favor the enantioselective recognition and substrate binding in 50C10. Substrate spectrum analysis revealed that 50C10 exhibited improved enantioselectivity toward diaryl ketones especially with halo- or other electron-withdrawing groups. As much as 500 mM CPMK could be asymmetrically reduced into chiral diaryl alcohols with ee of 99.4% and a space-time yield of 194 g·L-1·d-1 without addition of external NADP+. This study provides an effective mutagenesis strategy for the protein engineering of substrate specificity and enantioselectivity.

Structural Insight into Enantioselective Inversion of an Alcohol Dehydrogenase Reveals a "polar Gate" in Stereorecognition of Diaryl Ketones

Diaryl ketones are important building blocks for synthesizing pharmaceuticals and are generally regarded as "difficult-to-reduce" ketones due to the large steric hindrance of their two bulky aromatic side chains. Alcohol dehydrogenase from Kluyveromyces polyspora (KpADH) has been identified as a robust biocatalyst due to its high conversion of diaryl ketone substrate (4-chlorophenyl)(pyridine-2-yl)ketone (CPMK) with a moderate R-selectivity of 82% ee. To modulate the stereoselectivity of KpADH, a "polarity scanning" strategy was proposed, in which six key residues inside and at the entrance of the substrate binding pocket were identified. After iterative combinatorial mutagenesis, variants Mu-R2 and Mu-S5 with enhanced (99.2% ee, R) and inverted (97.8% ee, S) stereoselectivity were obtained. The crystal structures of KpADH and two mutants in complex with NADPH were resolved to elucidate the evolution of enantioselective inversion. Based on MD simulation, Mu-R2-CPMKProR and Mu-S5-CPMKProS were more favorable in the formation of prereaction states. Interestingly, a quadrilateral plane formed by α-carbons of four residues (N136, V161, C237, and G214) was identified at the entrance of the substrate binding pocket of Mu-S5; this plane acts as a "polar gate" for substrates. Due to the discrepancy in charge characteristics between chlorophenyl and pyridine substituents, the pro-S orientation of CPMK is defined when it passes through the "polar gate" in Mu-S5, whereas the similar plane in wild-type is blocked by several aromatic residues. Our result paves the way for engineering stereocomplementary ADH toward bulky diaryl ketones and provides structural insight into the mechanism of stereoselective inversion.

Chiral thiophosphoramide catalyzed asymmetric aryl transfer reactions for the synthesis of functional diarylmethanols

In this investigation, chiral thiophosphoramide 3d was easily prepared from chiral (1R,2R)-1,2-diphenylethylenediamine and then applied as an efficient chiral ligand in the catalytic asymmetric arylation reactions of various aromatic aldehydes. The corresponding diarylmethanol products were produced with good to excellent yields (up to 98%) and enantioselectivities (up to 94%). The recovery of chiral ligand 3d could be as high as 96%.