284686-92-6

Usage

Appearance

Colorless liquid

Odor

Slightly sweet

Uses

Intermediate in the synthesis of pharmaceuticals and agrochemicals, solvent in chemical reactions, building block in the production of other organic compounds

Solubility

Low in water

Toxicity

Low to moderate

Safety precautions

Handle with care and follow safety guidelines

Upstream product

• 50-00-0 formaldehyd 
• 402-50-6 1-trifluoromethyl-4-vinyl-benzene 
• 103108-04-9 2-(α,α,α-trifluoro-p-tolyl)propanal 
• 67-56-1 methanol 
• 2968-93-6 2-(4-trifluoromethylphenyl)ethanol 
• 178180-81-9 2-methyl-2-(4-(trifluoromethyl)phenyl)oxirane 
• 709-63-7 1-(4-trifluoromethylphenyl)ethanone 
• 135325-18-7 methyl 2-(4-(trifluoromethyl)phenyl)acetate 
• 125670-61-3 α-methyl-4-(trifluoromethyl)benzeneacetic acid methyl ester 

Downstream Products

• 134904-86-2 2-Methyl-2-(4-trifluoromethylphenyl)acetic acid 
• 284686-89-1 ethyl 4-methyl-2-(ethoxycarbonyl)-4-p-trifluoromethylphenyl-2-butenoate 
• 103108-04-9 2-(α,α,α-trifluoro-p-tolyl)propanal 

Relevant academic research and scientific papers

Highly efficient NHC-iridium-catalyzed β-methylation of alcohols with methanol at low catalyst loadings

The methylation of alcohols is of great importance since a broad number of bioactive and pharmaceutical alcohols contain methyl groups. Here, a highly efficient β-methylation of primary and secondary alcohols with methanol has been achieved by using bis-N-heterocyclic carbene iridium (bis-NHC-Ir) complexes. Broad substrate scope and up to quantitative yields were achieved at low catalyst loadings with only hydrogen and water as by-products. The protocol was readily extended to the β-alkylation of alcohols with several primary alcohols. Control experiments, along with DFT calculations and crystallographic studies, revealed that the ligand effect is critical to their excellent catalytic performance, shedding light on more challenging Guerbet reactions with simple alcohols. [Figure not available: see fulltext.].

Iron-Catalyzed β-Alkylation of Alcohols

β-Branched alkylated alcohols have been prepared in good yields using a double-hydrogen autotransfer strategy in the presence of our diaminocyclopentadienone iron tricarbonyl complex Fe1. The alkylation of some 2-arylethanol derivatives was successfully addressed with benzylic alcohols and methanol as alkylating reagents under mild conditions. Deuterium labeling experiments suggested that both alcohols (2-arylethanol and either methanol or benzyl alcohol) served as hydrogen donors in this cascade process.

Iron-Catalyzed Borrowing Hydrogen β- C(sp3)-Methylation of Alcohols

Herein we report the iron-catalyzed β-C(sp3)-methylation of primary alcohols using methanol as a C1 building block. This borrowing hydrogen approach employs a well-defined bench-stable (cyclopentadienone)iron(0) carbonyl complex as precatalyst (5 mol %) and enables a diverse selection of substituted 2-arylethanols to undergo β-C(sp3)-methylation in good isolated yields (24 examples, 65% average yield).

Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α-Substituted Aldehydes: Atom-Efficient Access to Enantiopure (S)-Profens and Profenols

The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2-arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an ′optimal compromise′ in the reaction outcome. The biocatalytic system could be applied to a variety of 2-arylpropanals and granted access in a redox-neutral manner to enantioenriched (S)-profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co-substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom-efficiency was exemplified by the conversion of 75 mM of rac-2-phenylpropanal with 0.03 mol% of HLADH in the presence of ～0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD+), yielding 28.1 mM of (S)-2-phenylpropanol in 96% ee and 26.5 mM of (S)-2-phenylpropionic acid in 89% ee, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg-scale, with intact enantiopurities. (Figure presented.).

Stereodivergent coupling of aldehydes and alkynes via synergistic catalysis using Rh and Jacobsen's amine

We report an enantioselective coupling between α-branched aldehydes and alkynes to generate vicinal quaternary and tertiary carbon stereocenters. The choice of Rh and organocatalyst combination allows for access to all possible stereoisomers with high enantio-, diastereo-, and regioselectivity. Our study highlights the power of catalysis to activate two common functional groups and provide access to divergent stereoisomers and constitutional structures.

Stereodivergent Coupling of Aldehydes and Alkynes via Synergistic Catalysis Using Rh and Jacobsen's Amine

We report an enantioselective coupling between α-branched aldehydes and alkynes to generate vicinal quaternary and tertiary carbon stereocenters. The choice of Rh and organocatalyst combination allows for access to all possible stereoisomers with high ena

Accessible protocol for asymmetric hydroformylation of vinylarenes using formaldehyde

We report herein on an accessible protocol for the asymmetric hydroformylation of vinylarenes using formaldehyde as a substitute for syngas. The regioselectivity (branched/linear = up to 96/4) and enantioselectivity (up to 95% ee) can be attributed to the use of chiral Ph-bpe as a ligand. This journal is

Use of a robust dehydrogenase from an archael hyperthermophile in asymmetric catalysis-dynamic reductive kinetic resolution entry into (s)-profens

Described is an efficient heterologous expression system for Sulfolobus solfataricus ADH-10 (Alcohol Dehydrogenase isozyme 10) and its use in the dynamic reductive kinetic resolution (DYRKR) of 2-arylpropanal (Profen-type) substrates. Importantly, among the 12 aldehydes tested, a general preference for the (S)-antipode was observed, with high ee's for substrates corresponding to the NSAIDs (nonsteroidal anti-inflammatory drugs) naproxen, ibuprofen, flurbiprofen, ketoprofen, and fenoprofen. To our knowledge, this is the first application of a dehydrogenase from this Sulfolobus hyperthermophile to asymmetric synthesis and the first example of a DYRKR with such an enzyme. The requisite aldehydes are generated by Buchwald-Hartwig-type Pd(0)-mediated α-arylation of tert-butyl propionate. This is followed by reduction to the aldehyde in one [lithium diisobutyl tert-butoxyaluminum hydride (LDBBA)] or two steps [LAH/Dess-Martin periodinane]. Treatment of the profenal substrates with SsADH in 5% EtOH/phosphate buffer, pH 9, with catalytic NADH at 80 °C leads to efficient DYRKR, with ee's exceeding 90% for 9 aryl side chains, including those of the aforementioned NSAIDs. An in silico model, consistent with the observed broad side chain tolerance, is presented. Importantly, the SsADH-10 enzyme could be conveniently recycled by exploiting the differential solubility of the organic substrate/product at 80 °C and at rt. Pleasingly, SsADH-10 could be taken through several thermal cycles, without erosion of ee, suggesting this as a generalizable approach to enzyme recycling for hyperthermophilic enzymes. Moreover, the robustness of this hyperthermophilic DH, in terms of both catalytic activity and stereochemical fidelity, speaks for greater examination of such archaeal enzymes in asymmetric synthesis.

1,2-asymmetric induction in the conjugate addition of organocopper reagents to γ-aryl α,β-unsaturated carbonyl derivatives

The diastereoselectivity in the conjugate addition of organocopper reagents to γ-aryl α,β-unsaturated carbonyl derivatives 8-14 was investigated. The syn-diastereoselectivity was obtained irrespective of the reagents type in the addition of 8, while the anti-diastereoselectivity was obtained in the addition of 10-14 with RCu and RCu(CN)Li (R=Me and Bu) and the syn-selectivity was produced in the addition of 10-14 with R2CuLi and R2Cu(CN)Li2. The reagent controlled and substrate dependent diastereoselectivity are explained by two different reaction pathways: either π-complex formation or ordinary nucleophilic addition. Reduction potentials of the Michael acceptors and electron donating ability of organocopper reagents control the reaction pathway. (C) 2000 Elsevier Science Ltd.