321-76-6

Upstream product

• 401-56-9 ethyl chlorofluoroacetate 
• 622-25-3 1-(2-chlorovinyl)benzene 
• 447-15-4 α-chloro-α-fluoroacetophenone 
• 100-58-3 phenylmagnesium bromide 

Downstream Products

• 394-97-8 (1,2-dichloro-2-fluoro-ethyl)-benzene 
• 351-78-0 β-fluorostyrene 

Relevant academic research and scientific papers

Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones

Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR).

Laccase/TEMPO-mediated system for the thermodynamically disfavored oxidation of 2,2-dihalo-1-phenylethanol derivatives

An efficient methodology to oxidize β,β-dihalogenated secondary alcohols employing oxygen was achieved in a biphasic medium using the laccase from Trametes versicolor/TEMPO pair, providing the corresponding ketones in a clean fashion under very mild conditions. Moreover, a chemoenzymatic protocol has been applied successfully to deracemize 2,2-dichloro-1-phenylethanol combining this oxidation with an alcohol dehydrogenase-catalyzed bioreduction. the Partner Organisations 2014.

Palladium-catalyzed intermolecular fluoroesterification of styrenes: Exploration and mechanistic insight

A novel palladium-catalyzed intermolecular oxidative fluoroesterification of vinylarenes has been developed using NFSI, one of the mildest electrophilic fluorinating reagents. The reaction presents an efficient synthetic pathway to afford a series of α-monofluoromethylbenzyl carboxylates in good to excellent yields. Rather than following an electrophilic fluorination pathway, the reaction is initiated through oxidation of Pd(0) to a Pd(ii) fluoride complex by NFSI, followed by fluoropalladation of a styrene to generate an α-monofluoromethylbenzyl-Pd intermediate. Generally, reductive elimination of benzyl-PdII complexes is favored with relatively strong oxy-nucleophiles to afford C-O bonds. This reaction, however, exhibited the opposite reactivity: strong acids with weak nucleophilicity, such as CF 3CO2H and CCl3CO2H, were prone to afford the fluoroesterification product, while weak acids with strong nucleophilicity, such as HOAc and BzOH, did not deliver the C-O bond product. Further mechanistic studies determined that Csp3-Pd(O2CR), a key intermediate, was generated through ionic ligand exchange between benzyl-Pd(NZ2) and CF3CO2H, and the final C-O bond was possibly formed through reductive elimination of a high-valent Csp 3-Pd(O2CR) complex via an SN2-type nucleophilic attack pathway.

Unusual reactions of Grignard reagents toward fluoroalkylated esters

Fluorine-containing esters were demonstrated to be convenient substrates for construction of the corresponding ketones by low temperature reaction with Grignard reagents followed by warming up to 0 °C, while heating the mixture up to 80 °C readily promoted the reduction of the ketones obtained by the generated magnesium alkoxides whose mechanism was speculated as Meerwein-Ponndorf-Verley type reduction by computational technique.