Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• formed. In this NMO-promoted PKR, monofluoroolefinic enyne 2 afforded the defluorinated cyclopentenone 7 in 37% yield. Similarly, trifluoromethyl-substituted olefin 3 also lost the chlorine atom upon cyclization to give 8 as a single diastereoisomer, albeit in a low 14% yield. The reaction of

• trifluoromethyl-substituted allylic alcohols 4 and 5 afforded the corresponding cyclized products 9 and 10 (31% and 34% yield, respectively) as inseparable mixtures of diastereoisomers. Finally, 1,6-enyne 6, bearing a 4-fluorophenyl group on the olefin, stereoselectively produced trans-oriented arylcyclopentenone

• cyclized product was observed when using the trifluoromethyl ketone derivative 12d. Secondly, PKR with enynes 14 containing fluorinated propargyl alcohol groups yielded diastereoisomeric mixtures of pyrrolidine ring-fused cyclopentenones 15 in good yields (67–85%) but low diastereoselectivities. Finally

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

• -aroyloxyaldehydes and trifluoroacetophenones, followed by ring opening with an amine or a reducing agent is described. The resulting β-trifluoromethyl-β-hydroxyamide and alcohol products are produced with reasonable diastereocontrol (typically ≈70:30 dr) and excellent enantioselectivity, and they can be isolated in

• moderate to good yield as a single diastereoisomer. Keywords: enantioselective catalysis; formal [2 + 2] cycloaddition; N-heterocyclic carbene; ring opening; trifluoromethyl group; Introduction The trifluoromethyl unit holds a prominent and privileged position within organic chemistry [1][2][3][4][5][6

• practical methodologies capable of the enantioselective incorporation of the trifluoromethyl unit into organic molecules has been developed widely [10][11][12], with a series of elegant organocatalytic strategies utilized toward these aims [13]. One general strategy for the organocatalytic construction of

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• temperature to yield alkyl, halo, and trifluoromethyl products, such as the examples 5 and 6 (Scheme 2). Chen, Wang and co-workers recently studied methods to reduce the exciton binding energy in linear conjugated polymers to enhance the charge separation and subsequent photocatalytic hydrogen evolution

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• - [55][56] phenanthridines was investigated. On the other hand, Umemoto’s reagent 7.2 was widely employed to introduce a trifluoromethyl group. In one instance, the visible-light irradiation of isocyanides 7.1 in the presence of excess 7.2 (4 equiv) and the Ru(bpy)32+ photoredox catalyst afforded the

• approach, sodium triflinate was adopted as the trifluoromethyl radical source along with diacetyl, that played the dual role of photomediator and reaction medium [60]. The same trifluoromethylated derivatives were obtained from 7.1 in the presence of CF3SO2Cl upon direct UV light irradiation by a Xe arc

• the same kind of substrates, 6-thiocyanatophenanthridines were isolated in discrete to excellent yields, in the presence of ammonium thiocyanate (NH4SCN) as the thiolating agent [68]. A very peculiar case is that described in Scheme 8 for the synthesis of 6-(trifluoromethyl)-7,8-dihydrobenzo[k

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• , and trifluoromethyl they smoothly took part in the three-component reaction and provided the desired products 6ja–na in moderate yields. It is noteworthy that benzaldehydes containing a halogen atom such as fluorine, chlorine, bromine, and iodine in the para and meta-positions were also compatible

Recent synthesis of thietanes

• Jiaxi Xu

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

• reactions) of alkenes and thiocarbonyl compounds are another important route for the synthesis of thietanes [15][16], especially, spirothietanes [17][18]. The formal [2 + 2] cycloadditions of hexafluorothioacetone and olefins are also applied in the preparation of bis(trifluoromethyl)-containing thietanes

• for the preparation of multiple substituted thietanes, including fused and spirothietanes. 3.2 Synthesis via the formal thermal [2 + 2] cycloadditions involving hexafluorothioacetone The formal thermal [2 + 2] cycloadditions have also been applied in the synthesis of bis(trifluoromethyl)thietanes from

• 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane-generated bis(trifluoromethyl)thioacetone with various olefins in nucleophilic solvents DMF or DMSO. Previously, the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (363) and quadricyclane (218) was carried out in diglyme in the presence of CsF

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• (Scheme 1A). This property might be responsible for stronger binding affinities of trifluoromethoxylated compounds with the active sites in enzymes, proteins, or other biomolecules [8][9]. Several procedures for the synthesis of trifluoromethyl aryl ethers were reported from the mid-1900s, mostly based on

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• performed with the sterically crowded thiocarbonyl S-methanide 1, derived from 2,2,4,4-tetramethyl-3-thioxocyclobutanone and extremely electron-deficient ethylenes 2 such as (E)- and (Z)-dialkyl dicyanobutenoates (R = CO2Me) [6], tetracyanoethylene (R = CN) [7] or (E)- and (Z)-1,2-bis(trifluoromethyl

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• dehydrogenation of the side chain attached to C=NO fragment was observed. Under the action of the TMSCF3/trichloroisocyanuric acid/TCCA/CuOAc/CsF system β,γ-unsaturated oximes 146 undergo oxidative cyclization to form substituted isoxazolines 147 with a trifluoromethyl group (Scheme 49) [138]. The authors note

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• afforded the corresponding products 2f–h in a yield of 82–89%. The compounds 1e and 1i, bearing a trifluoromethyl group, gave complex mixtures, and the expected products 2e and 2i were not obtained, which suggests that this reaction was sensitive to the electronic nature of the substituent of the

• with the imidazopyridines 1b–d, f, and h, bearing methoxy, methyl, and fluoro substituents as R1 or R2, gave the corresponding selenides 3b–d, f, and h in good to excellent yield (78–90%). In contrast, the imidazopyridines bearing a trifluoromethyl group gave complex mixtures from which the expected

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• CuCF2CH3 species. Pioneer works for the pentafluoroethylation and heptafluoropropylation using a copper-based reagent. Phen = 1,10-phenanthroline. a 19F NMR yields determined using 1,3-bis(trifluoromethyl)benzene as the internal standard. Pentafluoroethylation of (hetero)aryl bromides using the (Phen

• )CuCF2CF3 complex. 19F NMR yields were determined using 4-trifluoromethoxyanisole as the internal standard. aIsolated yields. Synthesis of pentafluoroethyl ketones using the (Ph3P)Cu(phen)CF2CF3 reagent. 19F NMR yields were given using 1,3-bis(trifluoromethyl)benzene as the internal standard. Synthesis of

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• synthesized through alkylation of the benzophenone imine of glycine ester 73, with perfluorinated benzylbromide 19c or 2,4-bis(trifluoromethyl)benzyl bromide (74) in the presence of 2,7-bis[O(9)-allylhydrocinchonidinium-N-methyl]naphthalene dibromide, to afford the fluorinated phenylalanine imines 75a,b with

• , m, or p-fluoro or (trifluoromethyl)phenylpyruvic acids 97a–f. The reaction was carried out in presence of 0.5 equiv of zinc(II) acetate in the presence of NaOMe. The initially formed complexes 98a–f underwent isomerization to 99a–f. Acid hydrolysis then gave the FPhe derivatives 53a,b, 53i, 81, and

• , chloro, bromo, methoxy, acetyl, cyano, nitro, and trifluoromethyl, were well-tolerated and afforded the corresponding anti-β-fluoro-α-amino acids 163a–l in moderate to excellent yields [78] (Scheme 40). 3. Synthesis of β,β-difluorophenylalanine derivatives of type IV via 2-phenyl-2,2-difluoroacetaldehyde

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• Chaudhuri [11][12][13] using well-defined copper complex 7, originally reported as a GAO mimic [20][21][22], we showed that this ability could be extended to the catalytic generation of trifluoromethyl radicals (Scheme 7) [29]. The synthetic efficiency of complex 7 in trifluoromethylation was reported on a

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

• , D-53121 Bonn, Germany 10.3762/bjoc.16.71 Abstract A new, mild and efficient protocol for the synthesis of trifluoromethyl(indolyl)phenylmethanols by the reaction of indoles with a variety of aromatic fluoromethyl ketones in the presence of K2CO3 (15 mol %) and n-Bu4PBr (15 mol %) in water. The

• into organic molecules can dramatically influence their physiochemical and biological properties in comparison with non-fluorinated analogs [18] (see compounds I and II in Figure 1). Many pharmaceuticals and agrochemicals developed in recent decades have either a fluorine atom or a trifluoromethyl

• group [19][20][21][22]. Given this, the development of a method for the incorporation of fluorine or trifluoromethyl group into organic molecules perhaps remains a current challenge in organic chemistry methodology. For example, trifluoromethyl-substituted (1H-indol-3-yl)methanol derivatives were

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• , which upon reaction with I-CH2F leads to the borylfluoromethylated product (e.g., 362–365, Scheme 58) [108]. Yin and co-workers described Cu(I)-catalyzed asymmetric additions to challenging trifluoromethyl and perfluoroalkyl ketones 370, starting with 1,3-enynes 369 and a slight excess of B2pin2 in THF

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• illustrated in Scheme 1. Difluorocyclopropane 8 can be directly prepared through a [2 + 1] carbene cycloaddition reaction. Thus, treatment of 12 with trimethyl(trifluoromethyl)silane (TMSCF3) and sodium iodide under refluxing conditions [13][14] gave the corresponding product 8 in one step and a 55% yield

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• group in the para-position gave a medium yield (27 82%). Aryl iodides containing one or two trifluoromethyl groups in their structure worked slightly less efficient producing arylaldehydes 28–30 with yields of 72–79%. It is worth noticing that a cyano group in the substrate stayed intact in the

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• attributed to the increased Brønsted acidity when the strong electron-withdrawing trifluoromethyl group was placed on the benzene ring of the arylboronic acid. Removing the boronic acid from the reaction system leads to a dramatic decrease in both yield and enantiocontrol (Table 1, entry 16). The challenge

Copper-catalyzed remote C–H arylation of polycyclic aromatic hydrocarbons (PAHs)

• Anping Luo,
• Min Zhang,
• Zhangyi Fu,
• Jingbo Lan,
• Di Wu and
• Jingsong You

Beilstein J. Org. Chem. 2020, 16, 530–536, doi:10.3762/bjoc.16.49

• variety of functional groups, including electron-donating methyl and methoxy groups, as well as electron-withdrawing ester, trifluoromethyl, fluoro, chloro, bromo, iodo and formyl groups. The arylating reactivity of aryliodonium salts with various substituents varied greatly due to the different

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• with the benzylic substrate. In 2018, Dilman and co-workers reported the catalytic formation of the trifluoromethyl radical through the photocatalytic reduction of a borate complex (Scheme 11) [28]. To carry out this reduction, the authors used the PF6 salt of the Sauvage catalyst under blue LED

• irradiation in MeOH to perform the trifluoromethyl methoxylation of styrene derivatives. The methodology was applied to a broad range of styrene derivatives, showing a good functional group tolerance. Noteworthy, α-, β-, and α,β-substituted styrenes were readily functionalized in good to excellent yields. To

• explain the reaction outcome, the authors suggested a reduction of the trifluoromethyl borate complex according to an SET with the excited copper(I) complex. The resulting substituted pyridyl radical eliminated a trifluoromethyl radical, which then reacted with the alkene. Then, the formed benzylic

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• available in some geographic areas where these materials have been used in practice. Such anions can be either bis(trifluoromethyl)sulfonylimides [5], aluminates [6] or sulfonates comprising long alkyl chains [5]. Alternatively, a barbiturate group positioned at the meso-position of the cyanine can also

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