Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• ) AgNO3, Me2CO, 75%. Racemic resolution of allenol 3 and synthesis of derivatives. a) Lipase AK, vinyl acetate, t-BuOMe, 30 °C, ((−)-(S)-3: 46%, 90% ee, (+)-(R)-9: 39%, 95% ee); b) N,N’-dicyclohexylcarbodiimide (DCC), dimethylaminopyridine (DMAP), (S) or (R)-(−)-α-methoxy-α-(trifluoromethyl)phenylacetic

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• systematically study the cross-coupling using the packed-bed reactor, we decided to equip the continuous-flow setup with a dedicated tool for in-line analysis. Such techniques enable rapid investigations of process-related parameters [34]. In particular, the presence of a trifluoromethyl group in the substrate

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• starting materials that incorporate functional groups with strong electron-withdrawing effects such as trifluoromethyl or chlorine, the imidazole product 16 was formed without any detectable amount of the triazole compound 15. In the cases when both products were observed, the ratio of the gained products

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• under the present reaction conditions providing 2d and 2e in 70% and 57% yields, respectively, with high diastereoselectivities. Substrates having electron-withdrawing groups such as ester (1f) and trifluoromethyl (1g) on the para-position of the aryl moiety afforded the desired products in good yields

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• halogen groups at the 6-position of the imidazopyridine ring were tested and gave the desired products 4ba–ea in fair to good yields (Table 2, entries 8–11). Conversely, imidazopyridine 1f with an electron-withdrawing trifluoromethyl group did not yield the corresponding product 4fa, because the

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , trifluoromethyl radicals and its longer-chain analogues, share a common electrophilic character and a stabilizing stereoelectronic effect [14], we envisioned that the “dummy group” methodology could be translated into the formation of sought after perfluoroalkyl radicals (Scheme 1). In this work, we report the

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• % yield. At the same time, arenes containing electron-withdrawing groups (such as halogen and trifluoromethyl) also give the corresponding products 3e–h in moderate yields with the meta substituted isomers as the major products. Interestingly, only the meta product was detected when (trifluoromethyl

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• catalytic polymerization of ε-caprolactone (123) was turned ON. The chloride was readily removed by adding sodium tetrakis[(3,5-trifluoromethyl)phenyl]borate (NaBArF) and as result catalysis was turned OFF again. Along this protocol, Mirkin et al. have developed a variety of allosterically modulated

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• of DAS 1i containing a trifluoromethyl group in the arylidene ring (Table 1, entry 9). In the latter case, the negative effect of the presence of the electron-withdrawing group also manifested itself in a significant decrease in the yield of the target dimer 2 due to the formation of unidentified

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• , such as 7-chloro-4-(4-trimethylsilylethynyl-1-pyrazolyl)quinoline at 100 ppm which gave a 100% curative effect in barley infected with barley powdery mildew [23]. A statistical model to predict the structural requirement of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)chloroquine derivatives to inhibit

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• reacted with two equiv 3-nitro-5-(trifluoromethyl)benzyl bromide (2) in the presence of a base to afford the dinitro compounds 3a–f in moderate to excellent yields (Scheme 1a). The diminished yield for product 3d was probably caused by the large steric hindrance of the 3-pentyl substituent. Reduction of

• 5-methyl (8i), 5-methoxy (8k), 6- or 7-fluoro (8l,m), 5,6-difluoro (8n), 5-, 6- or 7-chloro (8p–r), 5-, 6-, or 7-bromo (8t–v), and 7-trifluoromethyl (8w), all reactions completed within 36–48 h and afforded the products in good to excellent yields with 60–75% ee. In contrast, the reaction was

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• hours, which provides an environmentally friendly access to 3,4,5-trisubstituted isoxazoles, an important class of structures found in numerous bioactive natural products and pharmaceuticals. Additionally, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a

• chlorides to form furoxans also known as 1,2,5-oxadiazole 2-oxides, a class of structures with important biological activities due to their unique electronic nature and coordination ability. Keywords: environmentally friendly; furoxans; 1,2,5-oxadiazole 2-oxides; trifluoromethyl-substituted isoxazoles

• the nucleophilic addition and successive cyclization to happen. In addition, we further explored the scope of substrates with a trifluoromethyl group, a strong electron-withdrawing substituent, instead of methyl, an electron-donating group, in the 1,3-diketone starting materials (Table 2). The

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• collected in Supporting Information File 1): good yields were observed for 4-methylacetophenone (2b, 97%, Figure S9), 3-methoxyacetophenone (2c, 87%, Figure S10), 4-chloroacetophenone (2d, 76%, Figure S11), and 4-(trifluoromethyl)acetophenone (2e, 86%, Figure S12) and a moderate yield was obtained for 2

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• -lactones [146]. In 2020, Cai and co-workers reported a three-component intermolecular trifluoromethyl-esterification of activated alkenes 115 with NaOTf and aryl carboxylic acids 178 (Scheme 39) [147]. Notably, the use of NaOTf as a CF3 source, compared to pre-prepared trifluoromethylating agents like

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• good yields (81–94% yields). It was noteworthy that p-QMs bearing functional groups, such as methyl, methoxy, tert-butyl, fluoro, chloro, bromo, and trifluoromethyl were well compatible under the optimal reaction conditions. The efficiency of this method was not affected by the pattern of substituents

• ring of p-QMs 1 with functional groups such as alkyl, fluoro, bromo, trifluoromethyl, and thiophenyl was generally well tolerated (4a–g). Further, it should be noted that other activated methylene isonitriles such as methyl isocyanoacetate (2b) were also compatible with the reaction conditions

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• , Brazil Laboratório de Bioinorgânica e Materiais Porfirínicos, Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil 10.3762/bjoc.17.191 Abstract A new series of ten examples of Schiff bases, namely (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6

• -yl)imino)methyl)phenols 3, was easily synthesized with yields of up to 91% from the reactions involving a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines 1 and 4(5)-R1-substituted salicylaldehydes 2 – in which alkyl/aryl/heteroaryl for 2-R-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4

• interesting luminescent properties [14] that have attracted great interest because of their potential applicability in the composition of organic light-emitting diodes (OLED), organic solar cells (OSC), and biomolecular markers [15][16]. Moreover, the trifluoromethyl substituent (CF3) is an interesting

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• both 10e and 10b starting from amine 15b2. The same trend concerning relative yields between regioisomers can be observed for fluorenones bearing the electron-withdrawing trifluoromethyl group in the same positions (see 10g, 10h, 10i1, and 10i2). This is rather surprising, as electronic effects exerted

• % combined yield) and 10q1/2 (57% combined yield) further illustrates, how electron-withdrawing substituents negatively impact the yield of the reaction. As evident from Scheme 5, the cyclization protocol is compatible with several functional groups (chloro, nitro, cyano, trifluoromethyl). In contrast, the

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• acidity of the hydrogen-bond donating unit. This notion has often been realized with substituted aryls such as 3,5-bis(trifluoromethyl)phenyl. Ellman introduced a different approach and developed N-sulfinylureas. An additional potentially useful feature is the stereogenic center on sulfur. tert

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• carbenes (NHC) In recent years, NHCs have been used as organocatalysts for a wide variety of reactions [62]. Wang et al. investigated the use of several 1,2,4-triazolo-annelated chiral NHCs as organocatalysts to catalyze enantioselective aza-MR between primary amines (100) and β-trifluoromethyl-β

• 104 to Bz-protected (E)-4-hydroxybut-2-enal 105 in the presence of (S)-α,α-bis[3,5-bis(trifluoromethyl)phenyl]-2-pyrrolidinemethanol trimethylsilyl ether as the organocatalyst (cat. 106) and using PhCO2H as the acid additive. Desired products were obtained in good yields ≈78% with excellent

• formation of HOMO raised dearomative aza-dienamine-type intermediates, which undergo direct aza-Michael addition to β-trifluoromethyl enones to afford N-functionalized heteroarenes 121 efficiently in moderate to excellent yields, albeit with low to fair enantioselectivity. However, asymmetric aza-Michael

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• giving 96% yield of (S)-98 with 97% ee. Impressively, raising the temperature to 160 °C for only 30 s gave 95% yield with 89% ee. The substrate scope revealed broad tolerance for aryl (except for p-trifluoromethyl) and aliphatic R groups, with yields and ee in excess of 90% in most cases. The Wulff group

• cyclohexyl R groups in the presence of silica gel at 80 °C (Figure 19b). The rearrangements proceeded well with electron-rich aryl groups, regardless of the position of substitution, but the reaction was especially slow for the electron-withdrawing para-trifluoromethyl derivative. A major advantage of the

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• 19y in 81% yield, albeit in a markedly slow time of 19 minutes. Both the electron-donating nature and the size of this alkyl group probably slow down the reaction. We were unfortunately not successful with other nonaromatic substituents, including trifluoromethyl and ethoxycarbonyl groups, since the

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• generate a trifluoromethyl radical and LnCuIISO2Cl (intermediate A in Scheme 8). The formed trifluoromethyl radical adds to the alkene moiety to deliver a new alkyl radical, which is trapped by the LnCuII-SO2Cl species. Free SO2Cl– decomposes rapidly to SO2 and Cl–. However, in this transformation, SO2Cl

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• (such as n-propyl and n-hexyl) groups under the standard conditions. 2-En-4-ynyl azides 1 bearing electron-donating substituents (such as methyl and methoxy groups) obviously worked better than those with electron-withdrawing (such as nitro, cyano, acetyl, and trifluoromethyl) groups. Meanwhile, they

• tandem reaction of 2-trifluoromethyl-1,3-enynes 36 with primary amines, affording various trifluoromethyl-substituted 3-pyrrolines [56]. Subsequently, they also developed a novel route for the synthesis of halogenated trifluoromethylated pyrroles 37 and 38 by sequential intermolecular hydroamination

• reaction of 2-trifluoromethyl-1,3-enynes 36 with aliphatic primary amines and the following NXS-mediated oxidative cyclization (Scheme 13) [57]. The method tolerated various substituted benzylamines, 2-phenylethanamines, isopropylamine, and other aliphatic chain-like amines. Furthermore, both furan-2

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• , i.e., benzyl and ethyl, slightly decreased the yields of the products (see 4n and 4o). Regrettably, when a substrate 2 bearing a strong electron-withdrawing nitro or trifluoromethyl group on the phenyl ring was employed, the reaction gave very complex side products under the standard conditions, and

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• catalysis and ketone HAT photocatalyst [66]. Here, the catalytic system composed of the ketone photocatalyst (4-methoxyphenyl)(4-(trifluoromethyl)phenyl)methanone (24), Ni(acac)2, 5,5’-dimethyl-2,2’-bipyridine (5,5’-diMe-bpy), Na2CO3 under visible light (CFL) irradiation was found to be optimal to provide

• and co-workers (Scheme 35) [113]. This defluorinative functionalization protocol set the stage for the introduction of gem-difluoroalkene motifs into α-amino C(sp3)–H sites. Interestingly, substrates having a trifluoromethyl group on the amide backbone enabled the functionalization of δ C(sp3)–H bonds