Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• ketones can result in a different kind of AMYs to address the issue. The reaction of trifluoromethyl ketones with glycine or α-substituted amino acids generated stabilized AMY 8 which underwent cycloaddition with maleimides to give 2-CF3-substituted pyrrolidines 9 in 50–76% yield (Scheme 5) [65]. Both the

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF3, HFC-23) was developed. The combination of fluoroform and KHMDS in triglyme at −40 °C was effective for this transformation, with good yields as high as 92%. Substrate scope of

• the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores

• under the reaction conditions was also explored. Keywords: fluoroform; greenhouse gas; HFC-23; trifluoromethyl ketones; trifluoromethylation; Introduction In recent decades, organofluorine molecules have received widespread attention in the field of medicinal chemistry [1][2][3][4]. The introduction

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• , Pittman, et al. investigated the protonation of a variety of trifluoromethyl ketones in a superacid [35][91]. Trifluoromethyl ketone protonation was observed by NMR spectroscopy at −60 °C in a superacidic FSO3H–SbF5–SO2 solution (Scheme 34). The 19F chemical shift variation for the generated oxygen

• et al. managed the enantioselective arylation of aromatic trifluoromethyl ketones 150 with (S)-TRIP (Scheme 37) [96]. A variety of CF3-substituted enantioenriched benzylic alcohols 61 were thus synthesized after the trapping of protonated CF3-substituted ketones 134 (Scheme 37). Interestingly, these

• , affording biaryl species 161. Using this strategy, several trifluoromethyl ketones 162 and alcohols 163 bearing heteroaryl substituents (i.e., benzothiazole, quinoline, isoquinoline, benzimidazole, or imidazole) prone to be protonated were elegantly converted into the corresponding alcohols 163 and biphenyl

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• , Br, Scheme 63) [114]. In this transformation, BX3 played a dual role as both a Lewis acid catalyst and a source of the halide ion nucleophile. This reaction resulted in the generation of the trifluoromethyl ketones 145 and halodifluoromethyl ketones 146 and 147 in high yields. As in the previous

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• stereogenic trifluoromethyl centers is through enantioselective addition of enolates or their equivalents to prochiral trifluoromethyl ketones (Figure 1A). Within this area, a common catalytic approach has utilized aliphatic ketones as enolate equivalents using prolinamide, cinchona, or hybrid catalysts that

• trifluoromethyl ketones (Figure 1C) [20]. Over the last twenty years, NHCs have been widely exploited as highly efficient organocatalysts that have found use in numerous applications and were the subject of many extensive reviews [21][22][23][24][25][26]. Among the most common reactive intermediates generated

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• be synthesized by Friedel–Crafts hydroxyalkylation reactions of indoles with trifluoromethyl ketones in the presence of either Lewis/Bronsted acid catalysts. Bandini et al. reported the trifluoromethyl hydroxyalkylation of indoles catalyzed by an organic base 2-tert-butyl-1,1,3,3-tetramethylguanidine

• trifluoroacetophenones did not significantly influence the yield of the reaction. The trifluoromethyl ketones having electron-rich heteroaromatics such as 2-(trifluoroacetyl)furan (2g) and 2-(trifluoroacetyl)thiophene (2h) gave the desired products 3g (97%) and 3h (98%) in excellent yields. Next, the role of fluorine in

• , entry 17) of 3a was isolated. These results suggest that the combination of K2CO3 (15 mol %)/n-Bu4PBr (15 mol %) is a suitable and efficient catalytic system for this reaction. Having the optimized conditions in hand, the substrate scope of the reaction was explored. At first, different trifluoromethyl

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• clinical trials for type 2 diabetes mellitus. Xu et al. also presented the similar ring-opening/trifluoromethylation of cyclopropanols for the synthesis of various β-trifluoromethyl ketones [103]. In this year, Loh et al. [104] and Zhu et al. [105] proposed a oxidative ring-opening and fluorination of

• -trifluoromethyl ketones 128 at room temperature and in an open flask (Scheme 33) [113]. The presented results provided an efficient and convenient method for the synthesis of diverse fulorinated ketones from cyclopropanols. In the same year, this group developed a similar copper-catalyzed ring-opening and

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• all components in air, the environmentally friendly nature, and the recycling of the aqueous medium. Subsequently, the group of Li and Duan [58] reported an efficient method for the synthesis of α-trifluoromethyl ketones via addition of CF3 to aryl(heteroaryl)enol acetates using readily available

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• as source of SCF3 for direct trifluoromethylsulfenylation. 1 Trifluoromethylation Csp3–CF3 bond-forming reactions Synthesis of α-trifluoromethyl ketones from alkenes: After their original reports on the trifluoromethylation of aromatics (see later in the text, Scheme 34) [16] and disulfides (Scheme

•  69) [20], Langlois and co-workers demonstrated that enol acetates 1a–c were converted into the corresponding α-trifluoromethyl ketones upon treatment with CF3SO2Na with tert-butyl hydroperoxide (TBHP) and a catalytic amount of copper(II) triflate (Scheme 1) [21]. The scope was rather narrow and

• , pyrimidine, thiophene, etc. the Maiti group reported an alternative approach toward α-trifluoromethyl ketones starting from (hetero)arylacetylenes 7 and also aliphatic terminal alkynes 8 (Scheme 5) [24]. The trifluoromethyl radical was generated from CF3SO2Na as indicated earlier, oxygen from air was the

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• , our research group demonstrated a highly regioselective synthesis of a series of trifluoromethylated tetrazolo[1,5-a]pyrimidines with potent antimicrobial activity [37]. The reaction between several β-alkoxyvinyl trifluoromethyl ketones [CF3C(O)CH=C(R)OCH3] (in which R = Ph, 4-F–C6H4, 4-Cl–C6H4, 4-Br

• structures for the current study are depicted in Table 3. The results were correlated with LUMO coefficient data of β-alkoxyvinyl trifluoromethyl ketones, in which the first nucleophilic attack of the 5-aminotetrazole amino group occurs in the C4 [37]. The absence of the tetrazolo[1,5-a]pyrimidine2

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• -workers disclosed the first enantioselective reaction of α-cyanoketones 118 to α,β-unsaturated trifluoromethyl ketones 119, utilizing a novel organocatalyst that they developed containing a piperazine moiety (S)-120 (Scheme 38) [58]. The reaction proceeded through a Michael addition to the unsaturated

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• selected group of asymmetric cross-benzoin reactions are described in the following section. An NHC-catalysed union of aryl aldehydes and aryl trifluoromethyl ketones was developed in the laboratory of Enders. This direct intermolecular cross-benzoin reaction proceeded with high yields and chemoselectivity

• [27]. The reaction furnished excellent yields of α-hydroxy-α-trifluoromethyl ketones 25 possessing a quaternary stereocentre. The homo-benzoin condensation between two aldehydes is reversible under the reaction conditions. This eventually leads to the selective formation of the observed cross-benzoin

• trifluoromethyl ketones were later developed using the chiral catalyst 27 (Scheme 13) [29]. The electron-deficient triazolium-derived NHC 23 mediated efficient and chemoselective cross-benzoin reactions of aldehydes and α-ketoesters to produce acyloin products endowed with a quaternary stereocentre [30

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• , such as perfluoroalkyl acetates, trifluoroacetic acid, chlorodifluoroacetates, trifluoromethyl ketones and hemiaminals of trifluoroacetaldehyde, are attractive perfluoroalkyl anion sources for aromatic perfluoroalkylation reactions. The generation of perfluoroalkylcopper from perfluoroalkyl carboxylic

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• -substituted α-trifluoromethyl β-ketoesters in good to excellent yields. In a second approach, 5 and tetrabutylammonium difluorotriphenylstannate were used for efficient electrophilic trifluoromethylation of various silyl enol ethers to give the corresponding α-trifluoromethyl ketones in good to high yields

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32