- Control of enantioselectivity of lipase-catalyzed esterification in supercritical carbon dioxide by tuning the pressure and temperature
-
The enantioselectivity of lipase-catalyzed esterification of 1-(p-chlorophenyl)-2,2,2-trifluoroethanol in supercritical carbon dioxide was controlled by tuning the pressure and temperature. The enantioselectivity was higher at low pressure and low temperature (E=60) than at high pressure and high temperature (E=10). At the density of 0.75 g/mL, a modified Eyring plot of ln E against 1/T was found to be linear, as expected from the theory on the effects of temperature on stereochemistry.
- Matsuda, Tomoko,Kanamaru, Ryuzo,Watanabe, Kazunori,Kamitanaka, Takashi,Harada, Tadao,Nakamura, Kaoru
-
-
Read Online
- Control on enantioselectivity with pressure for lipase-catalyzed esterification in supercritical carbon dioxide
-
The enantioselectivity of lipase-catalyzed esterification of 1-(p-chlorophenyl)-2,2,2-trifluoroethanol in supercritical carbon dioxide changed continuously from E = 10 to 50 by decreasing the pressure at 55°C. The effect of the solvent on enantioselectivi
- Matsuda, Tomoko,Kanamaru, Ryuzo,Watanabe, Kazunori,Harada, Tadao,Nakamura, Kaoru
-
-
Read Online
- Highly enantioselective construction of CF3-bearing all-carbon quaternary stereocenters: Hiral spiro-fused bisoxazoline ligands with 1,1′-binaphthyl sidearm for asymmetric Michael-type Friedel-Crafts reaction
-
A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared. The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields (up to 99%) and good to excellent enantioselectivies (up to > 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF3-β-disubstituted nitroalkene was favorable.
- Bao, Robert Li-Yuan,Fu, Kang,Shi, Lei
-
supporting information
(2021/11/27)
-
- A Hammett Study of Clostridium acetobutylicum Alcohol Dehydrogenase (CaADH): An Enzyme with Remarkable Substrate Promiscuity and Utility for Organic Synthesis
-
Described is a physical organic study of the reduction of three sets of carbonyl compounds by the NADPH-dependent enzyme Clostridium acetobutylicum alcohol dehydrogenase (CaADH). Previous studies in our group have shown this enzyme to display broad substrate promiscuity, yet remarkable stereochemical fidelity, in the reduction of carbonyl compounds, including α-, β- and γ-keto esters (d -stereochemistry), as well as α,α-difluorinated-β-keto phosphonate esters (l -stereochemistry). To better mechanistically characterize this promising dehydrogenase enzyme, we report here the results of a Hammett linear free-energy relationship (LFER) study across three distinct classes of carbonyl substrates; namely aryl aldehydes, aryl β-keto esters and aryl trifluoromethyl ketones. Rates are measured by monitoring the decrease in NADPH fluorescence at 460 nm with time across a range of substrate concentrations for each member of each carbonyl compound class. The resulting v 0 versus [S] data are subjected to least-squares hyperbolic fitting to the Michaelis-Menton equation. Hammett plots of log(V max) versus σ X yield the following Hammett parameters: (i) for p -substituted aldehydes, ρ = 0.99 ± 0.10, ρ = 0.40 ± 0.09; two domains observed, (ii) for p -substituted β-keto esters ρ = 1.02 ± 0.31, and (iii) for p -substituted aryl trifluoromethyl ketones ρ = -0.97 ± 0.12. The positive sign of ρ indicated for the first two compound classes suggests that the hydride transfer from the nicotinamide cofactor is at least partially rate-limiting, whereas the negative sign of ρ for the aryl trifluoromethyl ketone class suggests that dehydration of the ketone hydrate may be rate-limiting for this compound class. Consistent with this notion, examination of the 13 C NMR spectra for the set of p -substituted aryl trifluo romethyl ketones in 2percent aqueous DMSO reveals significant formation of the hydrate (gem -diol) for this compound family, with compounds bearing the more electron-withdrawing groups showing greater degrees of hydration. This work also presents the first examples of the CaADH-mediated reduction of aryl trifluoromethyl ketones, and chiral HPLC analysis indicates that the parent compound α,α,α-trifluoroacetophenone is enzymatically reduced in 99percent ee and 95percent yield, providing the (S)-stereoisomer, suggesting yet another compound class for which this enzyme displays high enantioselectivity.
- Berkowitz, David B.,Kudalkar, Gaurav P.,Lee, Joshua D.,Tiwari, Virendra K.
-
supporting information
p. 237 - 247
(2020/02/18)
-
- 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.
- Brüning, Fabian,Nagae, Haruki,K?ch, Daniel,Mashima, Kazushi,Togni, Antonio
-
supporting information
p. 10818 - 10822
(2019/07/31)
-
- Visible light-promoted umpolung coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines
-
Tertiary alcohols bearing a trifluoromethyl group are of considerable medicinal interest. Using an umpolung strategy, we herein report the first intermolecular reductive cross-coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines with the aid of a Br?nsted acid catalyst upon visible-light irradiation. This metal-free reaction is operationally simple and performed at ambient temperature, allowing access to desired tertiary alcohols with tri-/difluoromethyl groups in moderate to excellent yields. The commercially available and easily handled Hantzsch ester effectively serves as an electron donor, as well as a hydrogen atom source.
- Xu, Xiao,Min, Qing-Qiang,Li, Na,Liu, Feng
-
supporting information
p. 11017 - 11020
(2018/10/08)
-
- A method of manufacturing a trifluoromethyl group-containing compound
-
PROBLEM TO BE SOLVED: To provide a method for producing a trifluoromethyl group-containing compound useful as a synthetic intermediate for a pharmaceutical or an agricultural chemical product.SOLUTION: There is provided a method for producing a trifluoromethyl group-containing compound represented by the following general formula (2) which is obtained by reacting a carbonyl compound having a specific structure with trifluoromethane and an organic base in an organic solvent (wherein, Rrepresents a methyl group, an ethyl group, a linear, branched or cyclic alkyl group having 3 to 10 carbon atoms, a phenyl group, a substituted phenyl group, a naphthyl group, a substituted naphthyl group, an ethenyl group, a 2-phenylethenyl group, a 9-anthryl group or a hetero ring; Rrepresents a hydrogen atom, a methyl group or a phenyl group.)
- -
-
Paragraph 0046; 0050; 0051
(2018/02/10)
-
- Asymmetric Construction of Pyrrolidines Bearing a Trifluoromethylated Quaternary Stereogenic Center via CuI-Catalyzed 1,3-Dipolar Cycloaddition of Azomethine Ylides with β-CF3-β,β-Disubstituted Nitroalkenes
-
A direct and convenient method has been developed for the synthesis of optically active pyrrolidines bearing a quaternary stereogenic center containing a CF3 group at the C-3 position of the pyrrolidine ring. The synthesis system, CuI/Si-FOXAP-catalyzed exo-selective 1,3-dipolar cycloaddition of azomethine ylides with β-CF3-β,β-disubstituted nitroalkenes, provides pyrrolidines with high diastereoselectivities (up to >98:2 d.r.) and excellent enantioselectivities (up to >99.9 ee) and performs well for a broad scope of substrates under mild conditions.
- Tang, Li-Wei,Zhao, Bao-Jing,Dai, Li,Zhang, Man,Zhou, Zhi-Ming
-
supporting information
p. 2470 - 2477
(2016/09/13)
-
- Photoinduced additive-free trifluoromethylation of aromatic aldehydes with TMSCF3
-
We report herein a new and effective method for additive-free trifluoromethylation of aromatic aldehydes with TMSCF3. Normal acidic hydrolysis for desilylation in the workup process is not required in this transformation. This reaction presents
- Sun, Jing,Peng, Xinhua,Guo, Hao
-
supporting information
p. 797 - 800
(2015/01/30)
-
- 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.
- Huang, Huayin,Zong, Hua,Bian, Guangling,Song, Ling
-
p. 12614 - 12619
(2016/01/09)
-
- 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.
- Huang, Huayin,Zong, Hua,Bian, Guangling,Song, Ling
-
p. 835 - 839
(2015/08/18)
-
- Pesticidal compositions and processes related thereto
-
This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
- -
-
Page/Page column 45-46; 131
(2016/01/09)
-
- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
-
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Nematoda, Arthropoda, and/or Mollusca, processes to produce such molecules and intermediates used in such processes, compositions containing such molecules, and processes of using such molecules against such pests. These molecules may be used, for example, as nematicides, acaricides, insecticides, miticides, and/or molluscicides. This document discloses molecules having the following formula (“Formula One”).
- -
-
Paragraph 0140; 0146; 0147
(2015/12/30)
-
- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
-
This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
- -
-
Paragraph 0644-0645
(2014/06/25)
-
- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
-
This document discloses molecules having the following formula ("Formula One"): and processes associated therewith.
- -
-
Page/Page column 46; 47; 129
(2014/07/08)
-
- Highly efficient synthesis of aryl and heteroaryl trifluoromethyl ketones via o-iodobenzoic acid (IBX)
-
A two-step process for the synthesis of aryl and heteroaryl trifluoromethyl ketones from the corresponding aldehydes is described. Trifluoromethyl alcohols were prepared from aryl and heteroaryl aldehydes in excellent yields using catalytic amount of K2CO3. The trifluoromethyl alcohols were then oxidized conveniently and efficiently by o-iodoxybenzoic acid (IBX) under mild conditions to get the desired functionalized aryl and heteroaryl trifluoromethyl ketones.
- Cheng, Huicheng,Pei, Yu,Leng, Faqiang,Li, Jingya,Liang, Apeng,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
-
p. 4483 - 4486
(2013/07/26)
-
- The enantioselective trifluoromethylation of aromatic aldehydes by quaternary ammonium bromide and (IPr)CuF at low catalyst loading
-
A general catalytic enantioselective trifluoromethylation of aromatic aldehydes using (IPr)CuF and quinidine-derived quaternary ammonium salt as catalysts has been developed. A wide range of aromatic aldehydes are converted to the corresponding products in up to 92% yield and 81% ee at 2 mol% of catalyst loading.
- Wu, Shaoxiang,Guo, Jiyi,Sohail, Muhammad,Cao, Chengyao,Chen, Fu-Xue
-
-
- Preparative access to medicinal chemistry related chiral alcohols using carbonyl reductase technology
-
Libraries of highly enantioenriched secondary alcohols in both enantiomeric forms were synthesised by enzymatic reduction of their parent ketones using selectAZyme carbonyl reductase (CRED) technology. Commercially available CREDs were able to reduce a range of substrate classes efficiently and with very high enantioselectivity. Matching substrate classes to small subsets of CREDs enabled the fast development of preparative bioreductions and the rapid generation of 100-1500 mg samples of chiral alcohols in typically >95% ee and the majority in ≥99.0% ee. The conditions for small scale synthesis were then scaled up to 0.5 kg to deliver one of the chiral alcohols, (S)-1-(4-bromophenyl)-2-chloroethanol, in 99.8% ee and 91% isolated yield.
- Rowan, Andrew S.,Moody, Thomas S.,Howard, Roger M.,Underwood, Toby J.,Miskelly, Iain R.,He, Yanan,Wang, Bo
-
p. 1369 - 1381
(2013/12/04)
-
- Nucleophilic trifluoromethylation of carbonyl compounds: Trifluoroacetaldehyde hydrate as a trifluoromethyl source
-
A feasible nucleophilic trifluoromethylating protocol has been developed using trifluoroacetaldehyde hydrate as an atom-economical trifluoromethyl source. The reaction was found to be applicable to the nucleophilic trifluoromethylation of a broad spectrum of carbonyl compounds with satisfactory yields in general. DFT calculations have been performed to provide mechanistic insight into the present and related reactions employing 2,2,2-trifluoro-1- methoxyethanol and hexafluoroacetone hydrate.
- Surya Prakash,Zhang, Zhe,Wang, Fang,Munoz, Socrates,Olah, George A.
-
p. 3300 - 3305
(2013/06/27)
-
- A sterically demanding organo-superbase avoids decomposition of a naked trifluoromethyl carbanion directly generated from fluoroform
-
A simple strategy avoiding the decomposition of a naked trifluoromethyl anion to difluorocarbene by a sterically very demanding organo-superbase without the help of a trifluoromethyl anion reservoir such as DMF is reported. The direct non-metallic trifluoromethylation of carbonyl compounds using fluoroform in the presence of t-Bu-P4 base afforded trifluoromethyl alcohols in high yields.
- Kawai, Hiroyuki,Yuan, Zhe,Tokunaga, Etsuko,Shibata, Norio
-
supporting information
p. 1446 - 1450
(2013/05/09)
-
- Reduction of activated carbonyl groups using alkylphosphanes as reducing agents: A mechanistic study
-
A comprehensive mechanistic investigation on the reduction of activated carbonyl groups using alkylphosphanes as reducing agents has been conducted through a combination of experimental as well as computational studies. Both approaches show that this kind of reduction proceeds either through proton transfer from alkylphosphanes and cleavage by water during work-up or through another reaction pathway involving the participation of water at the initial stage and a two-fold proton transfer to afford the product. The reaction mechanism of the reduction of activated carbonyl groups using alkylphosphanes has been studied both experimentally and theoretically. The reduction was shown to proceed either through proton transfer from alkylphosphanes and cleavage by water during work-up or through the participation of water at the initial stage and a two-fold proton transfer.
- Wei, Yin,Liu, Xu-Guang,Shi, Min
-
experimental part
p. 2386 - 2393
(2012/06/04)
-
- Asymmetric trifluoromethylation of aromatic aldehydes by cooperative catalysis with (IPr)CuF and quinidine-derived quaternary ammonium salt
-
A general enantioselective trifluoromethylation of aldehydes has been developed using (IPr)CuF and quinidine-derived quaternary ammonium salt as the cooperative catalyst. Thus, a wide range of aromatic aldehydes have been converted to the corresponding products in up to 92% yield and 81% ee at 2 mol% of catalyst loading. The greatly enhanced activity and enantioselectivity result from the initiative generation of active [(IPr)CuCF3] as well as additional coordination activation of other copper species.
- Wu, Shaoxiang,Zeng, Wei,Wang, Qi,Chen, Fu-Xue
-
supporting information
p. 9334 - 9337
(2013/01/15)
-
- PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
-
This document discloses molecules having the following formula (“Formula One”): and processes associated therewith.
- -
-
Page/Page column 71
(2013/02/28)
-
- KYNURENINE PRODUCTION INHIBITOR
-
Provided is a kynurenine production inhibitor comprising a nitrogen-containing heterocyclic compound represented by formula (I): (wherein R50 and R51 may be the same or different and each represent a hydrogen atom or the like, G1 and G2 may be the same or different and each represent a nitrogen atom or the like, X represents formula (III): (wherein m1 and m2 may be the same or different and each represent an integer of 0 or 1, Y represents an oxygen atom or the like, and R6 and R7 may be the same or different and each represent a hydrogen atom or the like), R1 represents optionally substituted lower alkyl or the like, R2 represents a hydrogen atom or the like, and R3 represents optionally substituted lower alkyl or the like), and the like.
- -
-
Page/Page column 135
(2011/10/12)
-
- Nonenzymatic kinetic resolution of racemic 2,2,2-trifluoro-1-aryl ethanol via enantioselective acylation
-
Kinetic resolution of a series of 2,2,2-trifluoro-1-aryl ethanol with (R)-benzotetramisole as the catalyst has been investigated. The result showed that when the aryl group in the substrate was a phenyl (or a phenyl substituted by an electron-donating group) or a naphthyl (an extended phenyl) group, the system could give an s value higher than 20. Preparative KR examples demonstrated the applicability of this method in the preparation of some of enantiomerically pure 2,2,2-trifluoro-1-aryl ethanol or 2,2,2-trifluoro-1-aryl-ethyl iso-butyrate.
- Xu, Qing,Zhou, Hui,Geng, Xiaohong,Chen, Peiran
-
supporting information; experimental part
p. 2232 - 2238
(2009/07/11)
-
- Reduction of 2,2,2-trifluoro-1-arylethanones with alkyl phosphines
-
In the presence of alkyl phosphines, reduction of 2,2,2-trifluoro-1-arylethanones proceeded smoothly to give the corresponding reduction products in moderate to high yields at room temperature. The possible mechanism was discussed on the basis of deuteriu
- Shi, Min,Liu, Xu-Guang,Guo, Ying-Wen,Zhang, Wen
-
p. 12731 - 12734
(2008/03/15)
-
- Chemoselective reduction of ketones: Trifluoromethylketones versus methylketones
-
Treatment of an equimolar mixture of trifluoromethylketones (TFMKs) and methylketones (MKs) with Et2Zn resulted in selective reduction of the TFMKs in good yield. In contrast, treatment of an equimolar mixture of TFMKs and MKs with NaBH4 in the presence of CeCl3 in EtOH/H 2O (10:1) at -10°C reduced only the MKs.
- Sasaki, Shigeru,Yamauchi, Takayasu,Kubo, Hajime,Kanai, Masatomi,Ishii, Akihiro,Higashiyama, Kimio
-
p. 1497 - 1500
(2007/10/03)
-
- Trifluoromethylation of carbonyl compounds with trifluoromethyltrimethylsilane (Ruppert reagent) promoted by triphenyldifluorostannates
-
Nucleophilic trifluoromethylation of aromatic aldehydes and ketones with trifluoromethyltrimethylsilane is initiated with KF/n-Bu3MeN +HSO4-/Ph3SnF cocatalytic system in CH2Cl2 or with K[Ph3SnF2] in DMF.
- Borkin,Loska,Makosza
-
p. 1187 - 1191
(2007/10/03)
-
- Trifluoromethylation of carbonyl compounds with sodium trifluoroacetate
-
In the presence of copper(I) iodide as catalyst, a variety of carbonyl compounds, such as aldehydes, ketones and acid anhydrous, could be trifluoromethylated with sodium trifluoroacetate to give the corresponding alcohols in moderate to high yields, and a possible mechanism was proposed to explain the roles of catalyst and solvent in the reaction system.
- Chang, Ying,Cai, Chun
-
p. 937 - 940
(2007/10/03)
-
- Sodium trifluoroacetate: An efficient precursor for the trifluoromethylation of aldehydes
-
In a convenient and efficient procedure, the nucleophilic trifluoromethylation of aldehydes with sodium trifluoroacetate was achieved, using copper(I) halides as the catalyst.
- Chang, Ying,Cai, Chun
-
p. 3161 - 3164
(2007/10/03)
-
- N-heterocyclic carbene catalyzed trifluoromethylation of carbonyl compounds
-
(Chemical Equation Presented) A novel N-heterocyclic carbene (NHC) catalyzed trifluoromethylation reaction of carbonyl compounds was discovered. Both enolizable and nonenolizable aldehydes and α-keto esters undergo facile trifluoromethylation with TMSCF3 at room temperature in the presence of only 0.5-1 mol % of the commercially available NHC (1), providing CF3-substituted alcohols in good yields. Selective trifluoromethylation of aldehydes over ketones can be achieved under NHC catalysis. These conditions are mild and simple and tolerate a variety of functional groups.
- Song, Jinhua J.,Tan, Zhulin,Reeves, Jonathan T.,Gallou, Fabrice,Yee, Nathan K.,Senanayake, Chris H.
-
p. 2193 - 2196
(2007/10/03)
-
- Nucleophilic trifluoromethylation using trifluoromethyl iodide. A new and simple alternative for the trifluoromethylation of aldehydes and ketones
-
(Matrix Presented) A novel method for nucleophilic trifluoromethylation of aldehydes and ketones, based on photoinduced reduction of trifluoromethyl iodide by tetrakis(dimethylamino)ethylene (TDAE), is presented.
- Ait-Mohand, Samia,Takechi, Naoto,Medebielle, Maurice,Dolbier Jr., William R.
-
p. 4271 - 4273
(2007/10/03)
-
- A compact chemical miniature of a holoenzyme, coenzyme NADH linked dehydrogenase. Design and synthesis of bridged NADH models and their highly enantioselective reduction
-
An L-lactate dehydrogenase that requires coenzyme NADH catalyzes the enantioselective reduction of pyruvate to L-lactate in anaerobic glycolysis. As the first homochiral ansa-type NADH models, we designed the bridged NADH models 10a-c having a parapyridinophane structure for strictly mimicking the stereospecificity of hydrogen transfer in the biological asymmetric reduction with NADH. These models were synthesized in several steps from the corresponding bridged nicotinate 5 prepared by our novel pyridine-formation reaction of formyl-substituted (vinylimino)phosphorane 4 with methyl propiolate. The bridged NADH models 10a-c effected excellent biomimetic reduction at various temperatures in the presence of magnesium ion to achieve both the enantioselective and stereospecific reduction of the pyruvate analogues 12u-z into chiral lactate analogues 13u-z with 88-99% ee. The high enantioselectivity was almost completely dependent on the planar chirality of 10a-c but not on the nature of the substituents of their carbamoyl groups. The biomimetic reduction proceeded with retention of the planar chirality, showing that the bridged NADH models are useful for being recycled. An isotope experiment with the deuterated model (±)-10d confirmed the stereospecific hydrogen transfer, which is in good accordance with natural coenzyme characteristics. The model (S)-10c also exhibited good enantioselectivity for the reduction of activated ketones 14k-n into the corresponding chiral alcohols 15k-n with 79-89% ee. The simple bridged NADH model (S)-10c having both a primary carbamoyl group and a shielding bridge feigning an enzyme wall suggests a compact chemical miniature of a holoenzyme, coenzyme NADH linked dehydrogenase, in terms of the unique structure, high enantioselectivity, and recyclability.
- Kanomata, Nobuhiro,Nakata, Tadashi
-
p. 4563 - 4568
(2007/10/03)
-
- 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.
- Matsuda, Tomoko,Harada, Tadao,Nakajima, Nobuyoshi,Itoh, Toshiyuki,Nakamura, Kaoru
-
p. 157 - 163
(2007/10/03)
-
- A chiral triaminosulfonium salt: Design and application to catalytic asymmetric synthesis
-
The first chiral triaminosulfonium salt, tris((S,S)-3,4-diphenylpyrrolidino)sulfonium difluorotriphenylstannate, catalyzes trifluoromethylation of benzaldehyde with (trifluoromethyl)trimethylsilane to give the corresponding optically active alcohol with 52% ee.
- Kuroki, Yoshichika,Iseki, Katsuhiko
-
p. 8231 - 8234
(2007/10/03)
-
- Coupling of fluoroform with aldehydes using an electrogenerated base
-
Trifluoromethylated alcohols are easily obtained in a one pot electroreaction in which cathodic reduction of iodobenzene generates a strong base which deprotonates fluoroform, inducing its coupling with aldehydes.
- Barhdadi, Rachid,Troupel, Michel,Perichon, Jacques
-
p. 1251 - 1252
(2007/10/03)
-
- Reactions of Trifluoromethyl Bromide and Related Halides: Part 9. Comparison between Additions to Carbonyl Compounds, Enamines, and Sulphur Dioxide in the Presence of Zinc
-
A Barbier procedure, under moderate pressure, was used for the trifluoromethylation of various carbonyl compounds, starting from trifluoromethyl bromide and zinc in pyridine.Trifluoromethyl methanols were obtained from aldehydes and trifluoromethyl ketones from activated esters.Ethyl benzoate, or acetone, induced the formation of the solvated trifluoromethylzinc derivatives which did not react with carbonyl cpompounds.Consequently, the Barbier condensation in that case was considered to involve nascent organometallics reacting near the zinc surface.The reaction with sulphur dioxide, leading to trifluoromethanesulphinate, showed striking differences from that of carbonyl compounds.It was shown that the main pathway occcured in solution.This condensation was interpreted by the initial formation of sulphur dioxide radical anion, which reacts with trifluoromethyl bromide by a single-electron-transfer process.Attempts to condense iminium salts failed when a hydrogen atom was lacking in the α position.When the iminium ion can be transformed in situ to an enamine, a reaction occured, leading to α-trifluoromethyl ketones.This condensation was interpreted by a chain mechanism involving trifluoromethyl radicals.
- Tordeux, Marc,Francese, Catherine,Wakselman, Claude
-
p. 1951 - 1957
(2007/10/02)
-
- ELECTROCHEMICAL TRIFLUOROMETHYLATION OF CARBONYL COMPOUNDS
-
The electroreduction of CF3Br in DMF containing aldehydes or ketones, using a sacrificial zinc anode, affords the corresponding trifluoromethyl alcohols together with the unreactive organozinc species CF3ZnBr and (CF3)2Zn.The alcohols are obtained with good yields from aldehydes.With ketones the organozinc species are formed preferentially to the alcohols, but the addition of tetramethylene-diamine allows the alcohols to form with moderate yields.
- Sibille, S.,Mcharek, S.,Perichon, J.
-
p. 1423 - 1428
(2007/10/02)
-
- PALLADIUM AND NICKEL-CATALYZED PERFLUOROALKYLATION OF ALDEHYDES USING ZINC AND PERFLUOROALKYL HALIDES
-
A room temperature method for the conversion of perfluoroalkyl iodides to α-perfluoroalkyl carbinols under Pd or Ni catalysis is reported.The use of trifluoromethyl bromide provides an economical procedure for trifluoromethyl substituted carbinols.
- O'Reilly, Neil J.,Maruta, Masamichi,Ishikawa, Nobuo
-
p. 517 - 520
(2007/10/02)
-
- Reduction by a Model of NAD(P)H. 29. Kinetics and Isotope Effects for the Reduction of Substituted Trifluoroacetophenone
-
Kinetics for the reduction of substituted and unsubstituted α,α,α-trifluoroacetophenone by a model of NAD(P)H in acetonitrile in the presence and absence of a magenesium ion, a catalyst, has been studied.The catalyzed and uncatalyzed reactions show linear free-energy relationships.It is found that the magnesium ion retards the reaction of ceratain substituted trifluoroacetophenones.The kinetic isotope effect and the isotopic ratio in the product are also studied.These values vary depending on the substituent and on the presence or absence of the magnesium ion.The result indicates that there is at least one intermediate in the reaction and is discussed in relation to the stability of the intermediate as well as that of the transition states.
- Ohno, Atsuyoshi,Yamamoto, Hiroyuki,Oka, Shinzaburo
-
p. 2041 - 2045
(2007/10/02)
-
- Reduction by a Model of NAD(P)H. 34. Substituent Effect on Asymmetric Reduction of Trifluoroacetophenones
-
Substituted and unsubstituted α,α,α-trifluoroacetophenones were reduced by a chiral NAD(P)H-model (R,R-Me2PNPH).Both electron-releasing and -withdrawing substituents give better optical yields than unsubstituted compound.The result has been interpreted in
- Ohno, Atsuyoshi,Nakai, Jun-ichi,Nakamura, Kaoru,Goto, Takehiko,Oka, Shinzaburo
-
p. 3486 - 3488
(2007/10/02)
-
- The reduction of aryl trifluoromethyl ketones by sodium borohydride. The hydride transfer process
-
The rates of reduction of 17 aryl trifluoromethyl ketones by sodium borohydride in 2-propanol have been measured.The rho (ρ) value is 3.12, excluding the 4-amino and 4-dimethylamino groups, which both lower the rate to a greater extent than their ? values predict.The close correspondence between substituent effects for hydride addition in the methyl and trifluoromethyl series (excluding the amino groups) suggests that normal substituent effects are to be expected for oxidation processes involving hydride removal in trifluoromethyl compounds.The present results are consistent with the oxidation of aryl trifluoromethyl carbi ols by permanganate taking place by hydrogen atom abstraction.The effect of substituents on the rate of reduction of the trifluoromethyl ketones is almost identical to that on the equilibrium constant for formation of the ketone hydrates.The application of the reactivity-selectivity principle to the reduction reaction is also considered.Reduction of the 4-ethyl compound has ΔH = 2.7 kcal mol-1 and ΔS = -38 cal deg-1 mol-1.
- Stewart, Ross,Teo, K. C.
-
p. 2491 - 2496
(2007/10/02)
-
- The reduction of aryl trifluoromethyl ketones by N-carbamoylmethyl-1,4-dihydronicotinamide
-
The reaction of 15 aryl trifluoromethyl ketones with N-carbamoylmethyl-1,4-dihydronicotinamide has been studied in aqueous sulfolane buffer.The unsubstituted ketone and those containing electron-withdrawing groups in the ring have the following reaction characteristics: (a) a high yield of alcohol is obtained, (b) the observed reaction rate is independent of ring substituent; however, when corrections are made for degree of hydration of the ketones the rate is correlated with Hammett ? values with a rho of 1.98, (c) a secondary isotope effect of approximately 1.08 and primary isotope effects of 1.45-1.62 are observed at 43.4 deg C for the reaction of the dihydronicotinamide containing one or two atoms of deuterium at C-4, (d) ΔH = 15.2 kcal mol-1, and ΔS = -27.0 cal deg-1 mol-1 for the unsubstituted compound, uncorrected for ketone hydration; ΔS for reaction of the unhydrated ketone and dihydronicotinamide is estimated to be -45 to -50 cal deg-1 mol-1.The mechanism for the reduction is consistent with hydride transfer from reductant to oxidant, very possibly accompanied by blind-alley formation of an adduct between ketone hydrate and dihydronicotinamide.Ketones containing electron-donating groups in the ring react with the dihydronicotinamide in some undetermined way, giving little or no alcohol as product.
- Stewart, Ross,Teo, K. C.,Ng, L. K.
-
p. 2497 - 2503
(2007/10/02)
-