- HFO-1234yf as a CF3-Building Block: Synthesis and Chemistry of CF3-Ynones
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Reaction of low cost, readily available 4th generation refrigerant gas 2,3,3,3-tetrafluoropropene (HFO-1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3-trifluoropropynide, addition of which to a range of aldehydes formed CF3-alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess–Martin periodinane (DMP) to give substituted CF3-ynones with minimal purification required. Michael-type additions of alcohol and amine nucleophiles to CF3-ynones are rapid and selective, affording a range of CF3-enone ethers and enaminones in excellent yields with high stereoselectivity for the Z-isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF3-substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti-arthritis drug celecoxib from HFO-1234yf in just three steps.
- Murray, Ben J.,Marsh, Thomas G. F.,Yufit, Dmitri S.,Fox, Mark A.,Harsanyi, Antal,Boulton, Lee T.,Sandford, Graham
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supporting information
p. 6236 - 6244
(2020/09/15)
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- Highly Enantioselective [3 + 2] Annulation of 3-Butynoates with β-Trifluoromethyl Enones Promoted by an Amine-Phosphine Binary Catalytic System
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We report a highly enantioselective [3 + 2] annulation between 3-butynoates and β-trifluoromethyl enones, furnishing trifluoromethylated cyclopentenes with three contiguous stereogenic centers in good yields, high diastereoselectivities, and excellent enantioselectivities. A unique catalytic system consisting of a simple amine and a chiral phosphine was devised, and the synergistic play of Lewis basic amine and phosphine was crucial for alkyne isomerization and subsequent cyclization. The protocol disclosed herein allows facile activation of 3-butynoates in phosphine-mediated asymmetric transformations.
- Ding, Kuiling,Han, Zhaobin,Lu, Yixin,Ni, Huanzhen,Wong, Yee Lin,Wu, Mingyue
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supporting information
(2020/03/30)
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- A Remarkable Influence of a Trifluoromethyl Group on the Reactions of β-Mercaptoalcohols with Fluorinated α-Bromoenones
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Isomeric fluorinated α-bromoenones react with dinucleophilic β-mercaptoalcohols in CH2Cl2 at room temperature in the presence of Et3N in a multistep process. Depending on the position of the CF3 group, different O,S-heterocycles or non-cyclic products were obtained. With 3-bromo-1,1,1-trifluorobut-3-en-2-ones derivatives of 1,4-oxathianes were formed, but isomeric 2-bromo-4,4,4-trifluorobut-2-en-1-ones yielded 1,3-oxathiolanes or non-cyclic sulfides. The thia-Michael addition is proposed as the initial step of the reaction, and the final heterocyclization is governed by the location of the CF3 group.
- Obijalska, Emilia,Pawelec, Maria,Mlostoń, Grzegorz,Capperucci, Antonella,Tanini, Damiano,Heimgartner, Heinz
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p. 3716 - 3723
(2018/04/09)
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- The preparation and cycloaddition reaction of 1-sulfonyl-1-trifluoromethyl allenes
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A series of 1-sulfonyl-1-trifluoromethyl allenes were prepared for the first time from commercial available 2-bromo-3,3,3-trifluoropropene. Cycloaddition reaction of these trifluoromethylated allenes with nitrones occured readily under mild conditions, giving the corresponding trifluoromethylated isoxazolidines in high yields.
- Li, Jun-Li,Yang, Xian-Jin,Jiang, Min,Liu, Jin-Tao
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supporting information
p. 3377 - 3379
(2017/08/02)
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- Iron-Catalyzed Thiocyclization for the Synthesis of Trifluoro-methylated Benzothiophenes by C-H Functionalization of Aryl Disulfides
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An iron-catalyzed thiocyclization of propynols with aryl disulfides has been developed for the synthesis of trifluoromethylated benzothiophenes. The one-pot tandem reaction involves Meyer-Schuster -rearrangement of propynols and radical cyclization through C-H functionalization of aryl disulfides. A variety of 2-trifluoroacyl benzothiophenes were prepared in moderate to good yields with good functional-group tolerance.
- Lin, Yan-Feng,Wang, Chong,Hu, Bo-Lun,Qian, Peng-Cheng,Zhang, Xing-Guo
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supporting information
p. 707 - 712
(2017/03/21)
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- Stereospecific asymmetric N-heterocyclic carbene (NHC)-catalyzed redox synthesis of trifluoromethyl dihydropyranones and mechanistic insights
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N-Heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels-Alder reactions of α-aroyloxyaldehydes with β-trifluoromethyl enones generates synthetically useful dihydropyranones containing a stereogenic trifluoromethyl substituent in good yields (up to 81%) and excellent diastereoselectivity and enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific, with use of either (E)- or (Z)-β- trifluoromethyl enones forming syn- or anti-dihydropyranone products, respectively. Mechanistic studies through in situ kinetic analysis of the reaction reveal key differences in reactivity between chiral NHC precursor 1 and an achiral NHC precursor.
- Davies, Alyn T.,Taylor, James E.,Douglas, James,Collett, Christopher J.,Morrill, Louis C.,Fallan, Charlene,Slawin, Alexandra M. Z.,Churchill, Gwydion,Smith, Andrew D.
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p. 9243 - 9257
(2013/10/08)
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- Unusual behavior of the anionic species from (E)-1-chloro-3,3,3- trifluoropropene(HCFC-1233t)
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(E)-1-Chloro-3,3,3-trifluoropropene was smoothly deprotonated by MeLi at the position β to the CF3 group, and exclusive formation of propargylic alcohols was observed by addition of appropriate carbonyl compounds as long as up to 1.6 equiv. of
- Miyagawa, Akiko,Naka, Motoki,Yamazaki, Takashi,Kawasaki-Takasuka, Tomoko
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scheme or table
p. 4395 - 4399
(2010/01/07)
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- Novel generation of 3,3,3-trifluoropropynyllithium and transformation of the carbonyl adducts to trifluoromethyl-substituted allenes
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A novel method for the generation of 3,3,3-trifluoropropynyllithium is reported, which involves treatment of trifluoromethyl-substituted enol tosylate, prepared from 1,1-dichloro-3,3,3-trifluoroacetone, with two equivalents of butyllithium. Palladium-cata
- Shimizu, Masaki,Higashi, Masahiro,Takeda, Youhei,Jiang, Guofang,Murai, Masahito,Hiyama, Tamejiro
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p. 1163 - 1165
(2008/03/13)
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- Electronically promoted Payne rearrangement of 3-CF3-2,3- epoxyalcohols
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(Chemical Equation Presented) Smooth and selective Payne rearrangement was achieved for the above types of epoxyalcohols with a CF3 group so as to form thermodynamically more stable alkoxides, where the strongly electron-withdrawing nature of this moiety played a significantly important role and was proved to overcome increased steric instability of epoxides from syn-E to anti-Z isomers.
- Yamazaki, Takashi,Ichige, Tatsuro,Kitazume, Tomoya
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p. 4073 - 4076
(2007/10/03)
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- Hydrofluorocarbon 245fa: A versatile new synthon in alkyne chemistry
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The CFC replacement 1,1,1,3,3-pentafluoropropane (HFC 245fa) has been established as a convenient source of trifluoropropynyllithium under mild conditions; a range of novel and known trifluoropropynyl-containing systems has been prepared in a one-pot procedure.
- Brisdon, Alan K.,Crossley, Ian R.
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p. 2420 - 2421
(2007/10/03)
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- Synthesis of 3-Trifluoroethylfurans by Palladium-Catalyzed Cyclization-Isomerization of (Z)-2-Alkynyl-3-trifluoromethyl Allylic Alcohols
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Hydroiodonation of trifluoromethyl propargylic alcohols 1 regio- and stereoselectively produce (Z)-2-iodo-3-trifluoromethyl allylic alcohols 2. (Z)-2-Alkynyl-3-trifluoromethyl allylic alcohols 5, available through Pd(PPh3)4-mediated coupling of 2 and terminal alkynes 4, cyclize and subsequently isomerize to 3-trifluoroethylfurans 6 upon catalysis under PdCl2(CH3CN)2 in THF at 5-10°C.
- Qing, Feng-Ling,Gao, Wen-Zhong,Ying, Jiewen
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p. 2003 - 2006
(2007/10/03)
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- The first synthesis of 4-trifluoromethyl-2H-pyrans by palladium-catalyzed cyclization of (E)-3-alkynyl-3-trifluoromethyl allylic alcohols
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The cross-coupling of (Z)-3-iodo-3-trifluoromethyl allylic alcohols 4 with terminal alkynes 5 in the presence of Pd(PPh3)4 and CuI gave conjugated (E)-3-alkynyl-3-trifluoromethyl allylic alcohols 2 in high yield. 4-Trifluoromethyl-2H-pyrans 7 were prepared from the cyclization of 2 using PdCl2(CH3CN)2 catalysis. (C) 2000 Elsevier Science Ltd.
- Qing,Gao
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p. 7727 - 7730
(2007/10/03)
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- 2-Bromo-3,3,3-trifluoropropene: A facile trifluoromethylacetylene anion synthon
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The introduction of trifluoromethylacetylene units into organic compounds has been further studied and extended. The direct reaction of two equivalents of Lithium Diisopropylamide with 2-bromo-3,3,3-trifluoropropene gave lithium trifluoromethylacetylide, the anion of which was trapped in greater than 90% overall yield with a variety of electrophiles.
- Katritzky, Alan R.,Qi, Ming,Wells, Adam P.
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p. 145 - 147
(2007/10/03)
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- Modified Preparation Method of Trifluoromethylated Propargylic Alcohols and Its Application to Chiral 2,6-Dideoxy-6,6,6-trifluorosugars
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Convenient generation of 3,3,3-trifluoropropynyl anion was realized from 2-bromo-3,3,3-trifluoropropene, and the anion's reaction with various electrophiles proceeded in excellent isolated yields.One of the products, 1-(benzyloxy)-6,6,6-trifluoro-4-hexyn-3-ol (4b), was further employed for the diastereoselective construction of 2,6-dideoxy-6,6,6-trifluorosugars after enzymatic optical resolution and osmium dihydroxylation of the corresponding olefins.The strongly electron-withdrawing trifluoromethyl moiety, significantly affecting the nucleophilic nature of the neighbouring functionalities, allows to ready differentiation of hydroxy groups by routine chemical transfromation, which results in the shortening of the reaction sequence.
- Yamazaki, Takashi,Mizutani, Kenji,Kitazume, Tomoya
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p. 6046 - 6056
(2007/10/03)
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- FLUORINATED ACETYLENES. PART 7. PREPARATION AND SOME REACTIONS OF 4,4,4-TRIFLUOROBUT-2-YNOIC ACID AND 1-PHENYL-4,4,4-TRIFLUOROBUT-2-YN-1-OL
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Treatment of the salt CF3C CLi with alkyl chloroformates affords the compounds CF3C CCO2R (R=Et and CH2Ph) in relatively low yield and with gaseous carbon dioxide yields the acid CF3C CCO2H.Reaction of the acid with diazomethane gives the methyl ester which, with an excess of the reagent, undergoes regiospecific 1,3-dipolar cycloaddition to produce 3-carbomethoxy-4-trifluoromethylpyrazole and hence the 3- and 5-carbomethoxy-1-methyl-4-trifluoromethylpyrazoles.Oxidation of the alcohol CF3C CCH(OH)Ph (active MnO2) affords a 70:23 mixture of 3-benzoyl-2,4-bis(trifluoromethyl)-2-hydroxy-6-phenyl-α-pyran and E-1,3-dibenzoyl-2-trifluoromethylpropene (via the ketone CF3C CCOPh).
- Tajammal, Sabiha,Tipping, Anthony E.
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