123986-75-4Relevant academic research and scientific papers
Asymmetric Synthesis of Primary and Secondary β-Fluoro-arylamines using Reductive Aminases from Fungi
González-Martínez, Daniel,Cuetos, Aníbal,Sharma, Mahima,García-Ramos, Marina,Lavandera, Iván,Gotor-Fernández, Vicente,Grogan, Gideon
, p. 2421 - 2425 (2020)
The synthesis of chiral amines is of central importance to pharmaceutical chemistry, and the inclusion of fluorine atoms in drug molecules can both increase potency and slow metabolism. Optically enriched β-fluoroamines can be obtained by the kinetic resolution of racemic amines using amine transaminases (ATAs), but yields are limited to 50 %, and also secondary amines are not accessible. In order to overcome these limitations, we have applied NADPH-dependent reductive aminase enzymes (RedAms) from fungal species to the reductive amination of α-fluoroacetophenones with ammonia, methylamine and allylamine as donors, to yield β-fluoro primary or secondary amines with >90 % conversion and between 85 and 99 % ee. In addition, the effect of the progressive introduction of fluorine atoms to the α-position of the acetophenone substrate reveals the effect of mono-, di- and tri-fluorination on the proportion of amine and alcohol in product mixtures, shedding light on the promiscuous ability of imine reductase (IRED)-type dehydrogenases to reduce fluorinated acetophenones to alcohols.
A Remarkably Simple Route to Versatile Difluoromethylated Molecules
Kaneko, Sadanori,Yamazaki, Takashi,Kitazume, Tomoya
, p. 2302 - 2312 (1993)
Difluoroacetaldehyde ethyl hemiacetal (1), prepared from ethyl difluoroacetate and lithium aluminum hydride in diethyl ether, was found to be a potential difluoroethylating reagent for the preparation of a wide variety of difluoromethylated compounds.Compound 1 shows promise for use in the synthesis of carbinols prepared by the reaction of 1 with metal reagents or enol silyl ethers, the synthesis of amino acid ketones and β-lactams via the nucleophilic reaction of imines, and the synthesis of sugar analogues.
Photoreductive transformation of fluorinated acetophenone derivatives on titanium dioxide: Defluorination vs. reduction of carbonyl group
Kohtani, Shigeru,Kurokawa, Takuya,Yoshioka, Eito,Miyabe, Hideto
, p. 68 - 74 (2016)
Photoreductive transformation of mono- and di-fluoromethyl acetophenone (AP) derivatives on the P25 titanium dioxide (TiO2) has been studied in deaerated ethanol solution under UV irradiation. 2-Monofluoromethyl AP (MFAP) was stable in the dark and existed as keto form in ethanol, whereas 64% of 2,2-difluoromethyl AP (DFAP) transformed into hemiketal form (photocatalytically inactive form) under the same condition. Under the UV irradiation with the TiO2 particles, the reduction of MFAP afforded only the defluorinated ketone, while the reduction of DFAP provided not only defluorinated ketones but also a hydrogenated alcohol. The reduction of carbonyl group and defluorination of DFAP concurrently occurred on TiO2, in which the formation of MFAP was observed as an intermediate of the sequential defluorinations. These two parallel reactions were initiated by electron transfer from the surface defect sites (Tisd) to DFAP adsorbed on the TiO2 surface. A possible reaction mechanism for DFAP is proposed and discussed on the basis of thermodynamic data upon the C-F bond cleavage of anion radical species generated during the photocatalysis.
Fluorodesilylation of alkenyltrimethylsilanes: A new route to fluoroalkenes and difluoromethyl-substituted amides, alcohols or ethers
Greedy,Gouverneur
, p. 233 - 234 (2001)
A range of alkenyltrimethylsilanes are converted to alkenyl fluorides by reaction with one equivalent of Selectfluor (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)), or difluoromethyl-substituted alcohols, ethers or amides using an excess of Selectfluor in the presence of various nucleophiles.
Solvent selection in synthesis of 4-(1-arylfluoroethoxy)quinazolines and thienopyrimidines
Han, Jin,Sundby, Eirik,Hoff, B?ge H.
, p. 82 - 88 (2013)
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.
Novel fluorous prolinol as a pre-catalyst for catalytic asymmetric borane reduction of various ketones
Goushi, Sakiko,Funabiki, Kazumasa,Ohta, Masaya,Hatano, Keisuke,Matsui, Masaki
, p. 4061 - 4066 (2007)
Novel prolinol carrying two perfluorohexylethyl groups at the α-position was prepared from l-proline as a starting chiral substrate. Catalytic asymmetric reduction of various ketones, including mono-, di-, and trifluoromethylated acetophenones, using fluo
Redox-Neutral 1,3-Diol Synthesis by Base-Promoted Diastereoselective Alcohol-Aldolization
Quintard, Adrien,Rodriguez, Jean,Shao, Na
supporting information, p. 7197 - 7201 (2020/10/02)
In order to prepare more efficiently key 1,3-diol fragments, we have devised a base-promoted redox-neutral condensation of ketones with alcohols. This diastereoselective alcohol-aldolization enables bypassing the classical oxidation and reduction steps necessary for the preparation of this crucial backbone by an overall redox-neutral formal borrowing hydrogen process. The starting alcohols constitute both the precursors of the in situ generated reactive aldehydes and the hydride source necessary for the chemoselective reduction of the aldol adduct intermediates.
Efficient asymmetric synthesis of aryl difluoromethyl sulfoxides and their use to access enantiopure α-difluoromethyl alcohols
Batisse, Chloé,Céspedes Dávila, Maria F.,Castello, Marco,Messara, Amélia,Vivet, Bertrand,Marciniak, Gilbert,Panossian, Armen,Hanquet, Gilles,Leroux, Frédéric R.
, p. 3063 - 3079 (2019/05/07)
The -CHF2 moiety has shown a growing interest in pharmaceutical and agrochemical applications over the last few years. Its introduction is therefore a current research topic for organic chemists. Several groups have reported the synthesis of di
A kind of the geminally alkyl boric acid ester compound and its preparation method and application (by machine translation)
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Paragraph 0340-0347, (2019/02/13)
The invention discloses a geminally alkyl boric acid ester compound and its preparation method and application. The structure of the compound of formula (I) as shown; wherein R is or ; R1 Is phenyl, substituted phenyl, biphenyl or thiophene; R2 Hydrogen, halogen, hydroxy, C1 - 4 Alkyl, C1 - 4 Alkoxy, phenyl, substituted phenyl; R3 Is phenyl or substituted phenyl. The compound of the invention the structure is stable, at the same time with two alkyl and boric acid ester, can be used as a raw material, more simple, convenient, and rapid preparation in a pharmaceutically has high-value of the compound. In addition, the preparation of the compounds is simple, the preparation method of the reaction substrate has wide applicability, can be prepared a plurality of the geminally alkyl boric acid ester compound; at the same time, the method of the mild reaction conditions, without metal reagent, does not need high temperature or high pressure, does not need to be acid or alkali additive, and the reaction time is short, simple and convenient operation, after treatment is simple, is a high-efficient synthetic geminally halothane base boron ester compounds. (by machine translation)
Decarboxylative difluoromethylation of aldehydes with PhSO2CF2COOK: A facile and efficient access to difluoromethylated carbinols
Zhu, Yu-Jun,Lei, Zhong-Liang,Huang, Da-Kang,Lian, Bo,Liu, Zhen-Jiang,Hu, Xiao-Jun,Liu, Jin-Tao
supporting information, p. 3184 - 3187 (2018/07/13)
A novel decarboxylative difluoromethylation reaction of PhSO2CF2COOK with aldehydes under metal- and ligand-free conditions has been developed. The reaction is very mild and tolerates a wide range of aldehydes (both enolizable and non-enolizable aldehydes), providing a facile and efficient method for the synthesis of structurally diverse difluoromethylated carbinols in moderate to excellent yields.
