450-94-2Relevant academic research and scientific papers
Iridium-catalyzed efficient reduction of ketones in water with formic acid as a hydride donor at low catalyst loading
Liu, Ji-Tian,Yang, Shiyi,Tang, Weiping,Yang, Zhanhui,Xu, Jiaxi
supporting information, p. 2118 - 2124 (2018/05/24)
A highly efficient and chemoselective transfer hydrogenation of ketones in water has been successfully achieved with our newly developed catalyst. Simple ketones, as well as α- or β-functionalized ketones, are readily reduced. Formic acid is used as a traceless hydride source. At very low catalyst loading (S/C = 10:000 in most cases; S/C = 50:000 or 100:000 in some cases), the iridium catalyst is impressively efficient at reducing ketones in good to excellent yields. The TOF value can be as high as up to 26:000 mol mol-1 h-1. A variety of functional groups are well tolerated, for example, heteroaryl, aryloxy, alkyloxy, halogen, cyano, nitro, ester, especially acidic methylene, phenol and carboxylic acid groups.
Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of enantiopure aromatic alcohols
Alsafadi, Diya,Alsalman, Safaa,Paradisi, Francesca
, p. 9169 - 9175 (2017/11/15)
Enzymatic synthesis of enantiopure aromatic secondary alcohols (including substituted, hetero-aromatic and bicyclic structures) was carried out using halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This enzyme showed an unprecedented substrate scope and absolute enatioselectivity. The cofactor NADPH was used catalytically and regenerated in situ by the biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the conversion of aromatic ketones was markedly influenced by the steric and electronic factors as well as the solubility of ketones in the reaction medium. Furthermore, carbonyl stretching band frequencies ν (CO) have been measured for different ketones to understand the effect of electron withdrawing or donating properties of the ketone substituents on the reaction rate catalyzed by HvADH2. Good correlation was observed between ν (CO) of methyl aryl-ketones and the reaction rate catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst for the preparation of chiral aromatic alcohols of pharmaceutical interest.
Exploiting a beast in carbenoid chemistry: Development of a straightforward direct nucleophilic fluoromethylation strategy
Parisi, Giovanna,Colella, Marco,Monticelli, Serena,Romanazzi, Giuseppe,Holzer, Wolfgang,Langer, Thierry,Degennaro, Leonardo,Pace, Vittorio,Luisi, Renzo
supporting information, p. 13648 - 13651 (2017/11/06)
The first direct and straightforward nucleophilic fluoromethylation of organic compounds is reported. The tactic employs a fleeting lithium fluorocarbenoid (LiCH2F) generated from commercially available fluoroiodomethane. Precise reaction conditions were developed for the generation and synthetic exploitation of such a labile species. The versatility of the strategy is showcased in ca. 50 examples involving a plethora of electrophiles. Highly valuable chemicals such as fluoroalcohols, fluoroamines, and fluoromethylated oxygenated heterocycles could be prepared in very good yields through a single synthetic operation. The scalability of the reaction and its application to complex molecular architectures (e.g., steroids) are documented.
Versatile iridicycle catalysts for highly efficient and chemoselective transfer hydrogenation of carbonyl compounds in water
Talwar, Dinesh,Wu, Xiaofeng,Saidi, Ourida,Salguero, Noemí Poyatos,Xiao, Jianliang
supporting information, p. 12835 - 12842 (2015/03/30)
Cyclometalated iridium complexes are shown to be highly efficient and chemoselective catalysts for the transfer hydrogenation of a wide range of carbonyl groups with formic acid in water. Examples include α-substituted ketones (α-ether, α-halo, α-hydroxy, α-amino, α-nitrile or α-ester), α-keto esters, β-keto esters and α,β-unsaturated aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50000 at pH 4.5 and required no organic solvent. The protocol provides a practical, easy and efficient way for the synthesis of β-functionalised secondary alcohols, such as β-hydroxyethers, β-hydroxyamines and β-hydroxyhalo compounds, which are valuable intermediates in pharmaceutical, fine chemical, perfume and agrochemical synthesis. Water wonder: Iridicycle catalysts are versatile and allow the highly efficient and chemoselective transfer hydrogenation of a variety of carbonyl compounds, including problematic and challenging ones, with formate in neat water (see scheme).
Steric vs. electronic effects in the Lactobacillus brevis ADH-catalyzed bioreduction of ketones
Rodriguez, Cristina,Borzecka, Wioleta,Sattler, Johann H.,Kroutil, Wolfgang,Lavandera, Ivan,Gotor, Vicente
supporting information, p. 673 - 681 (2014/01/06)
Lactobacillus brevis ADH (LBADH) is an alcohol dehydrogenase that is commonly employed to reduce alkyl or aryl ketones usually bearing a methyl, an ethyl or a chloromethyl as a small ketone substituent to the corresponding (R)-alcohols. Herein we have tested a series of 24 acetophenone derivatives differing in their size and electronic properties for their reduction employing LBADH. After plotting the relative activity against the measured substrate volumes we observed that apart from the substrate size other effects must be responsible for the activity obtained. Compared to acetophenone (100% relative activity), other small substrates such as propiophenone, α,α, α-trifluoroacetophenone, α-hydroxyacetophenone, and benzoylacetonitrile had relative activities lower than 30%, while medium-sized ketones such as α-bromo-, α,α-dichloro-, and α,α-dibromoacetophenone presented relative activities between 70% and 550%. Moreover, the comparison between the enzymatic activity and the obtained final conversions using an excess or just 2.5 equiv. of the hydrogen donor 2-propanol, denoted again deviations between them. These data supported that these hydrogen transfer (HT) transformations are mainly thermodynamically controlled. For instance, bulky α-halogenated derivatives could be quantitatively reduced by LBADH even employing 2.5 equiv. of 2-propanol independently of their kinetic values. Finally, we found good correlations between the IR absorption band of the carbonyl groups and the degrees of conversion obtained in these HT processes, making this simple method a convenient tool to predict the success of these transformations. The Royal Society of Chemistry.
On the configurational stability of chiral, nonracemic fluoro- and iodo-[D1]methyllithiums
Kail, Dagmar C.,Malova Krizkova, Petra,Wieczorek, Anna,Hammerschmidt, Friedrich
, p. 4086 - 4091 (2014/04/17)
Enantiomerically pure fluoro-[D1]methyllithium and iodo-[D 1]methyllithiums of up to 92% ee were generated by transmetalation of the corresponding stannanes with MeLi in THF at various temperatures. The intermediate halo-[D1]methyllithiums were trapped with benzaldehyde or acetophenone already present in excess in the reaction mixture to either give halohydrins or to disintegrate to carbene. The fluoro-[D1] methyllithiums were found to be microscopically configurationally stable within the tested range of -95 to 0°C, but chemically only stable at temperatures below -95°C due to a rapidly increasing portion disintegrating to carbene. The iodo-[D1]methyllithiums were configurationally labile relative to the rate of addition to PhCHO at all temperatures tested (-95 to -30°C). Disintegration to carbene interfered as well. The microscopic configurational stability of enantiomerically pure fluoro-[D1]methyllithiums prepared by tin-lithium exchange in the presence of excess benzaldehyde or acetophenone has been investigated. Depending on the reaction temperature, a portion of the generated fluoro-[D1]methyllithiums was added to the electrophiles to give fluorohydrins; the remaining portions disintegrated to carbene and LiF (see scheme).
Microwave assisted fluorofunctionalization of phenyl substituted alkenes using selectfluor
Kumar, Anil,Singh, Tej Vir,Venugopalan, Paloth
, p. 72 - 77 (2013/06/05)
A rapid fluorofunctionalization of alkenes and diene using selectfluor has been uncovered. The olefins such as 1-phenyl ethene; 1,1-diphenylethene; (E)-1,2-diphenylethene; (E)-1,2-dinaphthylethene; 1,1,2-triphenylethene; 1,1,2,2-tetraphenylethene and 1,1,
Palladium-catalyzed intermolecular fluoroesterification of styrenes: Exploration and mechanistic insight
Peng, Haihui,Yuan, Zheliang,Wang, Hao-Yang,Guo, Yin-Long,Liu, Guosheng
, p. 3172 - 3178 (2013/07/26)
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.
Synthesis of enantiopure fluorohydrins using alcohol dehydrogenases at high substrate concentrations
Borzeicka, Wioleta,Lavandera, Ivan,Gotor, Vicente
, p. 7312 - 7317 (2013/08/23)
The use of purified and overexpressed alcohol dehydrogenases to synthesize enantiopure fluorinated alcohols is shown. When the bioreductions were performed with ADH-A from Rhodococcus ruber overexpressed in E. coli, no external cofactor was necessary to obtain the enantiopure (R)-derivatives. Employing Lactobacillus brevis ADH, it was possible to achieve the synthesis of enantiopure (S)-fluorohydrins at a 0.5 M substrate concentration. Furthermore, due to the activated character of these substrates, a huge excess of the hydrogen donor was not necessary.
Solvent selection in synthesis of 4-(1-arylfluoroethoxy)quinazolines and thienopyrimidines
Han, Jin,Sundby, Eirik,Hoff, B?ge H.
supporting information, p. 82 - 88 (2013/11/06)
The nucleophilic aromatic substitution of 4-chloroquinazoline and 6-bromo-4-chlorothieno[2,3-d]pyrimidine with 1-aryl-2-fluoroethanols as nucleophilies has been studied focusing on the use of carbonate bases in combination of environmental acceptable solvents. The conversion rate depended on the solvent properties, the acidity of the nucleophile and the nature of the base. By using acetonitrile as reaction medium and K2CO3 as base, 2,2,2-trifluoro-, 2,2-difluoro-, and 2-fluoro-1-phenylethanol could efficiently be coupled to 4-chloropyrimidines. Alternatively, employing Cs 2CO3, allowed for shorter reaction time for these substrates, and also couplings of the non-fluorinated alcohols proceeded well. tert-Butanol was also found to be a suitable reaction medium in transformation of the fluoro alcohols. Testing of hydrolytic stability of the 4-alkoxypyrimidines revealed that the fluorinated and nonfluorinated derivatives were labile under acidic conditions, whereas in basic media the fluoroalkoxy derivatives were more stable than their non-fluorinated counterparts.
