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

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• rise to [6,7]bicyclic ketones 9, and 10 and the linear acid chloride 13, respectively. We have also found that when the ketone is not present, the trifluoroalkyl substrate is converted into bicyclic vinyl chloride 17 when treated with AlCl3. We hope that this short communication will inspire other

• or reversed-phase chromatography) required. bComplex mixture. c5 Days. Proposed mechanism for the formation of dichloroalkene 6 from trifluoroalkanone 5. Formation of bicyclic ketones 9 and 10 from 1,1,1-trifluoroalkanone 5b using 7 equivalents of AlCl3. Conversion of 1,1,1-trifluoroalkanone 5n to

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

• ] (Scheme 38). In these reactions, oxygen-stabilized α-(trifluoromethyl)carbenium ions 142 are supposed to be generated by protonation or Lewis acid activation of the starting ketones. Klumpp et al. explored the reactivity of CF3-substituted superelectrophiles (defined as multiply charged cationic

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

• Ph3P+CF2−, which was used for the Wittig olefination of aldehydes and ketones. However, heating PDFA in nonpolar solvents (e.g., xylene at 90 °C) favors the dissociation of the ylide to release difluorocarbene which is able to effect the cyclopropanation of alkenes [34]. Trimethylsilyl

• was found to be superior to both CsF and KF as an initiator. Difluorocarbene generated from TFDA (25) also readily reacted with propargyl esters 27 at the triple bond (Scheme 13). The difluorocyclopropenes 28 were further converted into the difluorocyclopropyl ketones 29 by alkaline hydrolysis and

• opposite to the CF2 fragment and the formation of a 2,2-difluorohomoallyl cation. Cleavage of the distal bond. Ring opening of gem-difluorocyclopropyl ketones: The gem-difluorocyclopropyl ketones such as 106 and 108 underwent nucleophilic ring-opening reactions induced by thiolate nucleophiles. A distal

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• 10.3762/bjoc.17.24 Abstract We described herein a selective method to prepare α-organylthio esters and α-organylthio ketones by the reaction of β-keto esters with sodium S-benzyl sulfurothioate or sodium S-alkyl sulfurothioate (Bunte salts) under basic conditions in toluene as the solvent at 100 °C. When

• 4 equivalents of a base were used, a series of differently substituted α-thio esters were obtained with up to 90% yield. On the other hand, employing 2 equivalents of a base, α-thio ketones were achieved after 18 h under air. Furthermore, after a shorter reaction time, the isolation of keto–enol

• tautomers was possible, revealing them as significant intermediates for the mechanism elucidation. Keywords: α-alkylthio esters; α-alkylthio ketones; Bunte salts; C–C bond cleavage; β-keto esters; Introduction During the last ten years, sodium S-organyl sulfurothioates, also known as Bunte salts, were

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• alcohols with C7H15 as the residue R1 by Hoye et al. [15] and C9H19 as the residue R1 by the Sandford group [21], who recorded 80% and 76% isolated yield, respectively, of the corresponding ketones. Because these compounds were previously isolated inconveniently by preparative GLC [15] or distillation [17

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• the good yields in this step, both intermediates were obtained with excellent enantiomeric excesses (97% for R = n-C5H11 and 90% for R = CH3). Compounds 60a and 60b were converted to azido ketones 61a and 61b by Mitsunobu reaction, and then these azido ketones underwent cyclization to furnish

• bromide provided ketones (+)-99 and (+)-100, in diastereoisomeric excess of about 92%. N-sulfinyl-β-aminoketone ketal (+)-99 was subjected to Mannich cyclization, via treatment with 25 equivalents of ammonium acetate in acetic acid at 75 °C, generating (−)-euphococcinine (2) in 90% yield. A similar

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• hydrogen reservoirs [40], as reducing agents in various transformations, including the reduction of aldehydes, amides and ketones, reductive aminations, alkene hydroboration, and carbon bond forming reaction [41][42], as well as various boronate and borinic acid precursors [43][44][45][46][47]. More

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• toxic sulfur tetrafluoride [32] and the explosive (diethylamino)sulfur trifluoride (DAST) [33]. Although the 2010 report by Umemoto provided a method for the deoxyfluorination of a wide variety of substrates, including alcohols, ketones, and even carboxylic acids to the mono-, di-, and trifluoromethyl

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• the real extrusion of CO in diaryl ketones [48][49] or of SO2 in diaryl sulfones (Scheme 1c) [50]. Nevertheless, a recent publication demonstrated that a metal-free photoextrusion was feasible when starting from benzene sulfonamides I (Scheme 1d, path a) [51]. Following the same approach, sparse

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• trisubstituted acetophenones were also examined, and most of them could generate the desired products in moderate yields (7p−t). It was noted that heterocycles-substituted ketones also showed high reactivity in this reaction, and the corresponding products were obtained in good yields (7u–w). In the following

• acetophenones and 1,3-diaminopropane to synthesis 2‑arylpyridine derivatives.a Acid density of catalyst. Substrate scope of the ketones catalyzed by LSA-FAS-Cu. LS-FAS-Cu catalyzed synthesis of aminonaphthalene derivatives.a Synthesis of the 3-phenylisoquinoline from 11a and urea (12a).a Supporting Information

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• knowledge allows for structural predictions based on GC–MS data [17]. The deuterium labelling technique was also applied to other compound classes such as alkylbenzenes and ketones [18][19][20][21]. For terpenes, structural proposals can only be made based on the mass spectra for structurally less

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• . Hydrolysis of 6 furnishes the desired α-functionalised aldehydes 8 in excellent yields and enantioselectivities (12 examples, up to >99:1 er). Further work on this system expanded the scope to ketones [22] instead of aldehydes and varied the electron-withdrawing group to include fluorinated alkyl groups [23

• Tung et al. merged photoredox, cobalt, and amine catalysis towards the synthesis of α-functionalised ketones 21 from tetrahydroisoquinolines (THIQs) 22 and ketones 23 (Scheme 3) [28]. The proposed mechanism involves an oxidative quenching cycle using the [CoIII] catalyst to generate [CoII] and [Ru

• ketones 29 with 2-substituted indoles 30 as a precursor to imine 31, for the synthesis of indolin-3-ones 32 in good yields and excellent enantioselectivities (21 examples, up to >99:1 er) (Scheme 4a) [29]. Zhang et al. recently added to the scope of this family of reactions with their use of aldehydes

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• using various fluoroalkylated alkynes with 2-iodoaryl ketones via cobalt-catalyzed carbocyclizations (Scheme 1c) [21]. Although our previous work was practical to produce interesting fluoroalkylated indenol derivatives, some drawbacks still remain unsolved. Initially, the reaction showed a low

• corresponding trimer of the fluoroalkylated alkyne, as reported by our group [27]. Finally, only 2-iodoaryl ketones (R3 = Me, Cy, Ph) were applicable in this catalytic reaction, whereas the cycloaddition using 2-iodobenzaldehyde (R3 = H) did not work at all. Therefore, the development of practical protocols for

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• visible-light-inactive molecules using PSCats 3.1 Benzylic C–H fluorination A seminal paper in the field of transition-metal-free direct C–H fluorination comes from Chen and co-workers, who applied aryl ketones as PSCats [135]. They discovered that the choice of the PS impacted the selective formation of

• tolerated various electron-rich and electron-poor substituents, affording exclusively benzylic C(sp3)–H gem-difluorinated products in modest to excellent (33–95%) yield of 28b–h. The functional group tolerance was demonstrated by successful reactions of alkyl chlorides, ketones and a para-substituted MIDA

• process and could not be ruled out (Scheme 20). 3.3 Directing-group-guided C(sp3)–H fluorination 3.3.1 Ketones as directing groups: Related to the curious near-exclusive C2 selectivity of 1-phenylbutan-1-one as reported by Tan and co-workers [198], Lectka and co-workers reported highly selective

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation–cyclization cascade mediated by K₂S₂O₈

• Qiang Liu,
• Weibang Lu,
• Guanqun Xie and
• Xiaoxia Wang

Beilstein J. Org. Chem. 2020, 16, 1974–1982, doi:10.3762/bjoc.16.164

• oxa-Michael additions of 2’-hydroxychalcones [9][10], or through condensation cyclization reactions of o-hydroxyacetophenones with ketones/aldehydes [11][12], in addition to other alternative transformations [13][14]. Moreover, radical cascade cyclizations of o-allyloxybenzaldehydes by employing

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• most accessible approach to the synthesis of 5H-thiazolo[3,2-a]pyrimidine-5(7)-ones is the reaction of 2-thiouracil derivatives with α-halo ketones and α-halo acids, involving successive alkylation and condensation steps (Scheme 3) [17][18][19][20][21]. A convenient one-step synthesis of

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• -azido ketones in iPrOH in the presence of potassium ethylxanthate as a catalyst [28], (b) by exploiting the reaction of arylglyoxals with an excess amount of ammonium acetate in water [29], (c) by the cathodic reduction of 2-azido-1-phenylethanone in a DMF/LiClO4 medium [30], (d) by radical chain

• reactions of α-azido ketones with tributyltin hydride [31], or (e) by a modified Radziszewski’s synthesis when using phenylglyoxals, benzaldeydes, and ammonium acetate as ammonia source in acetic acid or methylene chloride or N,N-dimethylformamide as the solvent [32], there are no adequate studies covering

• putative azide tautomer 4, the latter deriving from the corresponding α-phenacyl azide precursor 2 via an acid-catalyzed enolization process [34]. The pyrolysis of α-azido ketones in conventional VOCs (trichlorobenzene) is known to take place under harsh conditions, which are based on heating the mixture

Synthesis and highly efficient light-induced rearrangements of diphenylmethylene(2-benzo[b]thienyl)fulgides and fulgimides

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Valerii V. Tkachev,
• Andrey N. Utenyshev,
• Olga Yu. Karlutova,
• Alexander D. Dubonosov,
• Vladimir A. Bren,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2020, 16, 1820–1829, doi:10.3762/bjoc.16.149

• heterocyclic aldehydes or ketones with methylene succinates followed by subsequent hydrolysis and dehydration processes. Under exposure of solutions or crystals of thus prepared hetaryl(aryl)-substituted dihydrofuran-2,5-diones to UV light, those bearing an isopropylidene fragment attached to the furandione

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• towards various functional groups such as aldehydes, ketones, and esters. Of note is that in some cases, partial hydrogenation of the double bond was observed, resulting probably from the generation of a ruthenium–hydride complex. However, this consecutive reactivity and the ratio between the olefin and

• ., the organic Acr–H2 molecule (Figure 23). In this study, 35 examples of the targeted coupling products were afforded in good to excellent yields. Various synthetically relevant functional groups, including halides, esters, amides, ethers, ketones, and aldehydes were compatible with the protocol. This

Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• the synthesis of 6-substituted-N2-aryl-1,6-dihydro-1,3,5-triazine-2,4-diamines via the reaction of aromatic amines, cyanoguanidine, and ketones which afforded the corresponding 1-aryl-1,6-dihydro-6-substituted-1,3,5-triazine-2,4-diamines in 21–56% yields followed by Dimroth rearrangement utilizing

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

• proceed via enamine intermediates (Figure 1B) [14][15][16][17][18][19]. The state of the art within this area has been recently demonstrated by Dixon and co-workers, who showed that bifunctional BIMP catalysts could promote the enantioselective addition of typically recalcitrant aryl ketones to

• 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

Photoredox-catalyzed silyldifluoromethylation of silyl enol ethers

• Vyacheslav I. Supranovich,
• Vitalij V. Levin and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 1550–1553, doi:10.3762/bjoc.16.126

• . Under the optimized conditions, a series of silyl enol ethers 2 were reacted with silane 1 (Figure 1). The reaction worked well with enol ethers derived from aromatic ketones, while those obtained from aliphatic ketones were ineffective. This may be ascribed to the decreased radical-stabilizing effect

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , monosubstituted and 1,1-disubstituted arylolefins could be effectively cleaved into the corresponding aldehydes or ketones. The proposed mechanism is that disulfide is split by visible light to form thiyl radicals, which catalyzes the combination of the olefin with O2 to form the intermediate dioxetane that

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116