Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• ; Introduction In recent years, the incorporation of fluorine or fluorinated motifs into organic molecules has gained widespread interest. This is mainly due to the new properties associated with the introduction of these modifications. In particular, chalcogen trifluoromethyl motifs are of prime interest since

• they confer very high lipophilicity [1][2]. In this context, transition-metal catalysis plays a key role in the formation of carbon–chalcogen trifluoromethyl bonds. Major advances have been made in the last ten years especially for C–OCF3 [3][4][5] and C–SCF3 [6][7][8] bond-forming processes. Today

• usually contain copper–chalcogen trifluoromethyl σ-bonds. Likewise, the research on new methods enabling the incorporation of SeCF3 has continuously been growing and today, a plethora of strategies have been reported [10][11]. Therein, the design of new catalysts and reagents is a key factor to foster the

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• . For this, we have compared the uncatalyzed Ireland–Claisen rearrangement with three hydrogen-bond-catalyzed reactions. As model H-bonding catalysts, we selected diphenylthiourea, Schreiner thiourea, and the corresponding squaramide with bis(trifluoromethyl)phenyl groups. We have evaluated both the (E

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• sensitive tunable luminophores and the observed aggregation-induced emission enhancement are currently under further investigation. Experimental Typical procedure for the cyclocondensation synthesis of compound 5d 1-Phenyl-3-[4-(trifluoromethyl)phenyl]prop-2-yn-1-one (3h, 1.40 g, 5.00 mmol), was placed in a

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• obtained with high selectivity by performing the reaction in the presence of scandium(III) triflate as a catalyst. 4,4,4-Trifluoromethylacetoacetic ester showed high reactivity in the current reaction forming the corresponding 5-hydroxy-5-trifluoromethyl-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine as a

• , 46.92; H, 5.06; N, 39.09%; found: C, 47.20; H, 5.35; N, 39.36%. Ethyl (5RS,6RS,7SR)-5-hydroxy-7-methyl-5-(trifluoromethyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine-6-carboxylate and ethyl (5SR,6SR,7SR)-5-hydroxy-7-methyl-5-(trifluoromethyl)-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidine-6-carboxylate

Small anion-assisted electrochemical potential splitting in a new series of bistriarylamine derivatives: organic mixed valency across a urea bridge and zwitterionization

• Keishiro Tahara,
• Tetsufumi Nakakita,
• Alyona A. Starikova,
• Takashi Ikeda,
• Masaaki Abe and
• Jun-ichi Kikuchi

Beilstein J. Org. Chem. 2019, 15, 2277–2286, doi:10.3762/bjoc.15.220

• electrochemical behavior of 1b (Figure 2, bottom). In the presence of n-Bu4NBArF4 (where ArF = 3,5-bis(trifluoromethyl)phenyl) as supporting electrolyte having a bulky counteranion, the potential splitting for 1b became less pronounced and decreased by 37 mV compared to that with n-Bu4NPF6. A decreased potential

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• has emerged as a powerful method for the construction of these compounds. This review attempts to describe the major advances in the transition-metal-catalyzed incorporation of fluorine, trifluoromethyl, difluoromethyl, trifluoromethylthio, and trifluoromethoxy groups reported between 2011 and 2019

• . Trifluoromethylation Transition-metal-catalyzed trifluoromethylation reactions have made great progress in the joint efforts of organic fluorination scientists and metalorganic chemists over the past decade. Introducing trifluoromethyl groups into organic molecules can significantly alter their properties, such as

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

• Kenta Tanaka,
• Yuta Tanaka,
• Mami Kishimoto,
• Yujiro Hoshino and
• Kiyoshi Honda

Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208

• addition, 2-methoxy and 2-trifluoromethyl-functionalized benzoyl chloride can be applied to the reaction (3c,d). The 4-methoxy group was also tolerated in the reaction (3e). Substrates with strong electron-withdrawing groups such as 4-trifluoromethyl, 4-nitro and 4-cyano groups reacted with moderate to

Multiple threading of a triple-calix[6]arene host

• Veronica Iuliano,
• Roberta Ciao,
• Emanuele Vignola,
• Carmen Talotta,
• Patrizia Iannece,
• Margherita De Rosa,
• Annunziata Soriente,
• Carmine Gaeta and
• Placido Neri

Beilstein J. Org. Chem. 2019, 15, 2092–2104, doi:10.3762/bjoc.15.207

• dialkylammonium axles [17][18][19][20][21][22][23][24][25][26] by exploiting the inducing effect of the superweak tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (TFPB) anion that gives free ‘naked’ dialkylammonium cations. In addition, we have reported interesting examples of endo-cavity complexation of

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• -bromoaryl)benzimidazoles 1a–i are given in Supporting Information File 1. The results of the cyclization are summarized in Figure 2. Products 4, 7, and 8, substituted with methyl and trifluoromethyl groups, were obtained in good yield. In contrast, compounds 6 and 9, substituted with chloro groups, had low

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• epoxide as a single diastereomer via in situ-generated methyl(trifluoromethyl)dioxirane and the reduction of the C-14 ketone in the presence of Eu(fod)3 to give triptolide (47%) together with its C-14 α-hydroxy epimer epi-triptolide (47%). In 2014, Li’s group reported a divergent synthesis for triptolide

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• )ethyl (1e) and N-(2-(3-(4-(trifluoromethyl)phenyl)ureido)ethyl) (1f) substituted 3,6-dihydroxyphthalimides to synthesize functionalized O6-coronarene macrocycles. Pleasingly, the 3,6-dihydroxyphthalimide substrates 1d and 1e underwent the same reaction to produce corona[6]arene macrocycles 3d and 3e in

Norbornadiene-functionalized triazatriangulenium and trioxatriangulenium platforms

• Roland Löw,
• Talina Rusch,
• Tobias Moje,
• Fynn Röhricht,
• Olaf M. Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1815–1821, doi:10.3762/bjoc.15.175

• the norbornadiene-substituted platform 1 (62%). The TOTA cation with the tetrakis(3,5-bis(trifluoromethyl)phenyl)borate anion (TOTA+ [BArF4]−, 8) was obtained by ion exchange of the TOTA tetrafluoroborate 7 (TOTA+ BF4−) to achieve a high solubility in organic solvents [14]. 3-Bromo-2

• ) crossection along the white line in (a). Syntheses of the norbornadiene TATA platform 1 and TOTA platform 3. a) TMS-acetylene, Pd(PPh3)4, Cu(I)I, Et3N, toluene, N2, 60 °C, 1.3 h; b) KOH, THF, N2, reflux, 5 h; c) sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF4), DCM, rt, 2 h; d) n-BuLi, THF, N2

Complexation of 2,6-helic[6]arene and its derivatives with 1,1′-dimethyl-4,4′-bipyridinium salts and protonated 4,4'-bipyridinium salts: an acid–base controllable complexation

• Jing Li,
• Qiang Shi,
• Ying Han and
• Chuan-Feng Chen

Beilstein J. Org. Chem. 2019, 15, 1795–1804, doi:10.3762/bjoc.15.173

• reaction of 4,4′-bipyridine with concentrated HCl in acetonitrile followed by counteranion exchange with sodium tetrakis[3,5-di(trifluoromethyl)phenyl]borate (NaBArF) in dichloromethane. The new compounds were confirmed by NMR spectroscopy and high-resolution mass spectrometry (Supporting Information File

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• cations are the α-trifluoromethyl [22][23][24], α-cyano [22][25][26][27][28][29], α-carbonyl [30][31][32][33], and α-phosphoryl [34][35] analogs of 9. Carbocations of type 9 will be examined in conjunction with the cyclopropylcarbinyl–cyclobutyl manifold. The third type of carbocation that will be

• trifluoromethyl-substituted cyclopropylcarbinyl systems were prepared by addition of the carbene derived from the diazoester 56 to vinyltrimethylsilane as shown in Scheme 12. Reduction of the ester mixture 57 with lithium aluminum hydride gave a chromatographically separable mixture of alcohols 58 and 59

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• trifluoromethyl sulfonyl ether bioactives. Comparison of log P values of comparative aryl thioether motifs [18]. α,α-Difluoroethyl thioether substrates for metabolism studies. Fluorometabolites 6–8 isolated after incubation of 4 with C. elegans. Ratios are the average of three incubations. The structure of 7 was

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• was produced in a low 31% yield. Electron-withdrawing groups such as a fluorine, bromine, chlorine, trifluoromethyl and a nitro group as well as electron-donating groups such as a methoxy group at the para-position were found to be well tolerated, as indicated by aryl cyclopropyl sulfides 1h–m which

• ) δ 7.39 (d, J = 8.4 Hz, 4H), 7.27 (d, J = 8.7, 4H). Cyclopropyl(4-(trifluoromethyl)phenyl)sulfane (1k). The general procedure was followed on 0.400 mmol scale starting from 4-(trifluoromethyl)benzenethiol (14k). The residue was purified on silica gel (100% Hex) to afford 1k (63.2 mg, 72%) as a light

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• -fluorophenyltriazolyl)methyl galactopyranoside 1b having an affinity of 170 ± 2 µM and fourfold better than for galectin-3 (Table 1). The (4-(trifluoromethyl)phenyltriazolyl)methyl galactopyranoside 1k displayed a comparable affinity of 240 ± 61 µM, but slightly lower selectivity over galectin-3. (1-Naphthyltriazolyl

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• sequence including one deprotection reaction. One functional unit is α-lipoic acid (ALA) for binding the dye to gold surfaces. It was introduced to the DAT scaffold by an amidation reaction. The other functional unit is a para-(trifluoromethyl)benzyl group for facile detection of the surface-bound material

• suitability for molecular surface labeling. Conclusion Two bifunctional diaminoterephthalate (DAT) fluorescence dyes have been prepared. One functional unit is α-lipoic acid (ALA) for binding the dye to gold surfaces. The other carries a trifluoromethyl group for facile detection of the surface-bound material

• by X-ray photoelectron spectroscopy (XPS). In the first of two target structures, compound 3, the fluorinated residue was introduced by reductive amination of mono-N-Boc-protected diethyl DAT 1 with para-(trifluoromethyl)-substituted benzaldehyde. After N-deprotection, the ALA unit was introduced by

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• -aminobenzothiopyranones containing 8-nitro and 6-trifluoromethyl substituents in low to moderate yields through the transformation of a 2-methylthio substituent under harsh conditions (method F, Scheme 1) [5]. In addition, the nucleophile imidazole could also react with 3-bromobenzothiopyranones to afford 2

• , the 2-position of the benzopyranone scaffold is easier to be attacked by nucleophiles than that the corresponding benzothiopyranone. We anticipate that the electron-withdrawing effect of a cyano, carbonyl, nitro or trifluoromethyl group, especially at the 3-position could render the sulfide, sulfinyl

• such as trifluoromethyl gave the desired products, e.g., 4m,n in high yields. Substrates bearing electron-donating groups also reacted with aliphatic amines giving products 4o–q in good yields. It was noted that the treatment of substrate 2 containing a chloro substituent with weaker nucleophilic

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• detected in the crude product. The reactions of β-ketoenamides KE60, KE61 and KE68 (R2 = tert-butyl or adamantanyl, R3 = methyl, trifluoromethyl or cyclopropyl) provided mixtures of oxazoles OX7, OX8 and OX10, respectively, and of 1,2-diketones DK4, DK5 and DK11 (Table 6, entries 9, 10, and 16). For

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• -withdrawing groups at the aromatic substuituent proceeded slowly, producing considerably lower yields of the corresponding products. For instance, multiple-substituted compound 1 (with a 3,5-disubstitued trifluoromethyl 1f) generated product 3f with a yield of 36% (88% brsm) after 24 h (Table 2, entry 5), but

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• )(aminocyclopropanes) 42 and 43, substituted by a p-fluorophenyl and a p-(trifluoromethyl)phenyl group, respectively, were isolated in moderate yield (53%). Moreover, (p-nitrophenylmethylene)cyclopropane 44 could not be obtained under these conditions [53]. These results indicate that the [3,3]-sigmatropic

• substituents at C2 were viable substrates. The sequence allowed access to benzylidenecyclopropane 58d (93%) and to (arylmethylene)cyclopropane 58e in excellent yield (90%), despite the presence of the electron-withdrawing trifluoromethyl substituent at the para-position of the aromatic ring. Some

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• dispersed over all loadings. No improvements in thermal properties were observed in the copolymers obtained. Another POSS-containing monomer – N-(propyl-POSS)-7-oxanorbornene-5,6-dicarboximide was tested in ring-opening metathesis copolymerization with 3-(trifluoromethyl)phenyl-7-oxanorbornene-5,6

• of polymers and copolymers with 3-(trifluoromethyl)phenyl-7-oxanorbornene-5,6-dicarboximide (Scheme 25) [48]. It was found that the increase in the content of POSS units in the copolymer results in a decrease in thermal stability and Tg values. TEM and AFM microimages show spherical POSS aggregates

• subsequent hydrogenation. ROMP of norbornenylethyl-POSS with 1,5-cyclooctadiene. Copolymerization of POSS-functionalized norbornene with DCPD. Copolymerization of tris(norbornenylethyl)-POSS with DCPD. Copolymerization of N-(propyl-POSS)-7-oxanorbornene-5,6-dicarboximide with 3-(trifluoromethyl)phenyl-7

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• , trifluoromethyl and ester, gave 75–95% yields of the corresponding products y-9–y-13, which were precursors for further transition metal-catalyzed cross-coupling reactions. To further explore the generality of this reaction, different substituted ortho-bromobenzoyl chlorides were then tested (Scheme 3). The ortho

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

• trifluoromethylation of cyclopropanols 91 to construct β-trifluoromethyl-substituted ketones 106 (Scheme 23) [101]. Additionally, a series of cyclopropanols with different functional R groups were successfully scaled up to 1 mmol. In this transformation, there exist two possible pathways to produce the target product

• 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