124095-23-4

Upstream product

• 124095-25-6 Acetic acid 2-chloro-2,2-difluoro-1-phenyl-ethyl ester 
• 384-67-8 2-chloro-2,2-difluoroacetophenone 
• 557-20-0 diethylzinc 
• 100-52-7 benzaldehyde 
• 340-03-4 2-chloro-2,2-difluoro-1-phenyl-ethan-1-ol 

Relevant academic research and scientific papers

Two Classes of Enzymes of Opposite Stereochemistry in an Organism: One for Fluorinated and Another for Nonfluorinated Substrates

Reduction of methyl ketones by dried cells of Geotrichum candidum (APG4) afforded (S)-alcohols in excellent enantiomeric excess (ee), whereas the reduction of trifluoromethyl ketones gave the corresponding alcohols of the opposite configuration also in excellent ee. The replacement of the methyl moiety with a trifluoromethyl group alters both the bulkiness and the electronic properties, the effect of which on the stereoselectivity was examined. No inversion in stereochemistry was observed in the reduction of hindered ketones such as isopropyl ketone, while the stereoselectivity was inverted in the reduction of ketones with electron-withdrawing atoms such as chlorine. The mechanism for the inversion in stereochemistry was investigated by enzymatic studies. Several enzymes with different stereoselectivities were isolated; one of them catalyzed the reduction of methyl ketones, and another with the opposite stereoselectivity catalyzed the reduction of trifluoromethyl ketones. Furthermore, both APG4 and the isolated enzyme were applied to the reduction of fluorinated ketones on a preparative scale, which resulted in the synthesis of chiral fluorinated alcohols with excellent ee.

Asymmetric Hydrogenation of Aryl Perfluoroalkyl Ketones Catalyzed by Rhodium(III) Monohydride Complexes Bearing Josiphos Ligands

The asymmetric hydrogenation of 2,2,2-trifluoroacetophenones and aryl perfluoroalkyl ketones was developed using a unique, well-defined chloride-bridged dinuclear rhodium(III) complex bearing Josiphos-type diphosphine ligands. These complexes were prepared from [RhCl(cod)]2, Josiphos ligands, and hydrochloric acid. As catalyst precursors, they allow for the efficient and enantioselective synthesis (up to 99 % ee) of chiral secondary alcohols with perfluoroalkyl groups. This system does not require an activating base for the hydrogenation of 2,2,2-trifluoroacetophenones. Additionally, the enantioselective C=O hydrogenations of 2-phenyl-3-(haloacetyl)-indoles, a class of privileged structures in medicinal chemistry, is reported for the first time.

Molecular Basis for the High Activity and Enantioselectivity of the Carbonyl Reductase from Sporobolomyces salmonicolor toward α-Haloacetophenones

In an effort to develop a practical method for the synthesis of optically pure 2,2,2-trifluoro-1-phenylethanol, we found that the carbonyl reductase (SSCR) from Sporobolomyces salmonicolor showed excellent activity and enantioselectivity toward the halogenated acetophenones. Especially, SSCR exhibited more than 1000 times higher activity toward α,α,α-trifluoroacetophenone than unsubstituted acetophenone, a strikingly different observation from the previously well-studied alcohol dehydrogenase (LBADH) from Lactobacillus brevis. Enzyme-substrate docking and site-directed mutagenesis studies revealed the molecular basis for the high enzyme activity and enantioselectivity of SSCR toward the α-halogenated acetophenones. The hydrogen bond of the Asn207 side chain with the substrate halogen atom and the XH/π interaction of the substrate phenyl group with the side chains of Ser222/Thr223 resulted in the formation of the highly reactive conformation of α-halogenated acetophenones in the active site of the enzyme. (S)-2,2,2-Trifluoro-1-phenylethanol was prepared in excellent isolated yield and enantiomeric excess from the reduction of α,α,α-trifluoroacetophenone with mutant T209A. These results suggest that tuning the interactions between the halogen atoms/phenyl group of the substrate and the amino acid residues of the enzyme would lead to valuable mutants for the practical synthesis of β-haloalcohols.

Catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl aromatic ketones with diethylzinc

Abstract The catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl ketones using diethylzinc as the β-hydrogen donor was developed with the use of phosphinamide chiral ligand. The corresponding alcohol products were afforded in good yields with up to 73% ee. This method was successfully applied to the chemo- and enantioselective reduction of α-methyl/trifluoromethyl diketone, affording 88% yield and 70% ee of the fluorinated hydroxylketone product.

Chemo- and Enantioselective Addition and β-Hydrogen Transfer Reduction of Carbonyl Compounds with Diethylzinc Reagent in One Pot Catalyzed by a Single Chiral Organometallic Catalyst

Using a single chiral phosphoramide-Zn(II) complex as the catalyst, the asymmetric β-H transfer reduction of aromatic α-trifluoromethyl ketones and enantioselective addition of aromatic aldehydes with Et2Zn in one pot were successfully realized, affording the corresponding additive products of secondary alcohols in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee) and the reduction products of α-trifluoromethyl alcohols in good to excellent yields with up to 77% ee.

A microbially-based approach for the synthesis of chiral secondary alcohols bearing the difluoromethyl or chlorodifluoromethyl group

A synthetic approach to both enantiomers of the secondary alcohols , involving the stereoselective hydrolysis of ester derivatives, is described.The absolute configurations of these difluoromethylated or chlorodifluoromethylated molecules were determined.