Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• % yield. Additional experiments were then carried out using N-methoxy-2-(prop-1-en-2-yl)benzamide with different substituents R2. Both electron-donating (methyl, alkoxy, dimethylamino) and electron-withdrawing substituents (fluoro, chloro, trifluoromethyl) were well tolerated on the phenyl ring and gave

• group (trifluoromethyl, fluoro, chloro) was located on the phenyl ring, various amounts of 4-substituted isoquinolinone derivatives 2k,m,n were observed along with the formation of 3h,j,k, respectively. Furthermore, a substrate containing a naphthalene unit was also compatible with the reaction

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• contained some other compounds, which have not been identified. Among the amines studied, amine A3 is less prone to oxidation (due to the electron-withdrawing effect of the trifluoromethyl group) and is the less basic; the presence of a lutidine base even more fastens deprotonation of the radical cation

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• trisubstituted alkenes (Figure 1). As described above, the electron density in the aryl rings does not seem to have a significant impact on the reaction, since alkenes possessing methyl 2, methoxy 5, and trifluoromethyl 6 groups were all high yielding. This observation was supported by the cyclic voltammetric

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V

• them easily because they normally require harsh fluorinating reagents. The synthesis of hypervalent iodine(V) fluoride 3 was reported by Amey and Martin in 1979 using the highly toxic gas, trifluoromethyl hypofluorite (Scheme 2A), and they later prepared bicyclic hypervalent iodine(V) fluoride 4 using

• contains two trifluoromethyl groups in the sidearm which could alter the electronic effects significantly. We therefore decided to prepare a small series of monocyclic trifluoro(aryl)-λ5-iodanes, where the sidearm substituents were changed stepwise from methyl to trifluoromethyl groups, so that we also

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• -(trifluoromethyl)aniline in conjunction with external ligand 5 facilitated the formation of a series of fluorinated α-amino acids. Xu and co-workers also disclosed a palladium-catalysed protocol for the fluorination of simple benzylic substrates bearing a bidentate directing group (Figure 8) [42]. Yields varied

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• used as an effective anti-inflammatory pharmaceutical [23]. On the other hand, organic thiocyanates usually serve as useful synthetic intermediates that can be conveniently converted to sulfur-containing derivatives including sulfides [24], disulfides [25], thiocarbamates [26], and trifluoromethyl

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• , Wang and co-workers [30] demonstrated the photomediated synthesis of γ,γ-difluoroallylic ketones by reacting trifluoromethyl alkenes and acids in the presence of PPh3 additive and iridium photocatalyst in basic medium (Scheme 3). This methodology was suitable for a wide range of carboxylic acids in the

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• electrophilicity. The products are finally generated by intramolecular formation of a semi-acetal. The yields were generally good (56–78%). The yields for pentafluoroethyl- and heptafluoropropyl-substituted derivatives were slightly better than the yields of trifluoromethyl-substituted derivatives which might be

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• properties of selected products, bis- and tris-alkynylated quinolines, were studied to gain insights into how the substitution pattern at different positions may alter the optical properties. Results and Discussion The starting material, 4,8-dibromo-2-(trifluoromethyl)quinoline (4), was synthesized from 2

• -bromoaniline (1a) and ethyl trifluoroacetoacetate (2), adapting a known procedure from Schlosser and Marull (Scheme 1) [17]. The cyclization of 1a with 2a chemoselectively afforded 8-bromo-2-trifluoromethyl-4-quinolone (3) rather than 8-bromo-4-trifluoromethyl-2-quinolone. Bromination of 3 with phosphoryl

• electronic push–pull interaction of the thiophene and the quinoline moieties via the alkyne. Finally, we focussed on the synthesis of tris-alkynylated quinolines starting from 3,4,8-tribromo-2-(trifluoromethyl)quinoline (11). Starting material 11 was synthesized in very good yield from quinolone 3 by

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• afford (trifluoromethyl)thioethers, while subsequent work focused on the direct deoxygenative synthesis of fluorinated thioesters from carboxylic acids [29][30][31]. In each case, the reactions proceeded smoothly under operationally simple conditions while BT-SCF3 and related BT-SRF reagents are easy-to

• -handle solids that can be readily produced on a multigram scale from relatively inexpensive starting materials. During the optimisation studies for the latter process with carboxylic acid substrates, in addition to the desired (trifluoromethyl)thioester products, small amounts of the corresponding acyl

• , reacting BT-SCF3 with carboxylic acids 1 under similar conditions provides (trifluoromethyl)thioesters 3 via a concerted deoxytrifluoromethylthiolation process from tetrahedral intermediate A affording thiocarbamate by-product B [31]. To test whether thioester species could act as intermediates in the

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• this reaction, regardless of the electronic nature and position of the substituents. The desired 3,4-benzocoumarin products 3ba–ma were obtained in yields of 21–59%. Notably, substituents such as halogens (F, Cl, and Br), methyl, methoxy, and trifluoromethyl groups at the ortho-, meta-, or para

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• than those in CD2Cl2). However, this did not hold true uniformly. When a commercially available electron-acceptor ligand known as “Jackiephos” (bis(3,5-bis(trifluoromethyl)phenyl)(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine was used as the AuNTf2 salt (6a), in CD2Cl2, the reaction rate

• further (see Supporting Information File 1, Figure S19). This comparison reveals that the Jackiephos supported gold accelerates the reaction more than (PhO)P(o-biphenyl)2 does, although this may be in part an anion effect [7]. The bis(trifluoromethyl)aryl substituent is expected to be more electron

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• the formation of the corresponding olefin [12]. Another area of application of olefins 1a,b is based on C=C double bond addition reactions. As early as 1968, Atherton and Fields showed that (Z)- and (E)-butenes 1a,b reacted with diazotrifluoroethane to give 3,4,5-tris(trifluoromethyl)pyrazoline [13

• demonstrated that 1,1,1,4,4,4-hexafluorobut-2-ene reacts with dithietane, sulfur and KF with the formation of the corresponding 1,3-dithiole [16]. Also, a recent patent presents a method for the preparation of 5,6-bis(trifluoromethyl)-1,2,4-triazine-3-carboxylic acid ethyl ester starting from 1,1,1,4,4,4

• completion of the reaction and subsequent treatment of the reaction mixture with 2 N hydrochloric acid, 2,3-bis(trifluoromethyl)-1-(4-fluorophenyl)prop-2-ene-1-ol (10) was detected in the 19F NMR spectrum. It should be noted that, in addition to the unreacted starting aldehyde 9, the formation of olefin 1b

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• with aryl thiols [70]. Further studies showed that 4-(trifluoromethyl)thiophenol (97) could act as a catalytic reductant in the aminodecarboxylation reaction of NHPI esters derived from α-amino acids [71] (Scheme 19). Accordingly, visible light irradiation of a mixture consisting of N-Boc-alanine NHPI

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, Spain 10.3762/bjoc.20.21 Abstract An efficient multicomponent reaction of newly designed β-trifluoromethyl β-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper

• -catalyzed conditions has been developed, which affords various unsymmetrical β-trifluoromethyl N,N-diacyl-β-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of β-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an

• efficient way for the synthesis of β-trifluoromethyl β-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of β-trifluoromethyl β-diazo esters. Keywords: β-carbonyl diazo; copper catalyst; fluoroalkyl diazo; Mumm rearrangement; unsymmetrical β-diacylamino

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China 10.3762/bjoc.20.12 Abstract A visible-light-promoted research protocol for constructing dihydropyrido[1,2-a]indolone skeletons is herein described proceeding through a cascade cyclization mediated by trifluoromethyl

• enables a rapid access to heterocycles containing a trifluoromethyl group. Keywords: cascade reaction; indole derivatives; photocatalysis; radical chain process; trifluoromethylation; Introduction Dihydropyrido[1,2-a]indolone (DHPI) skeletons are commonly found in natural products and pharmaceutical

• an electron-withdrawing functional moiety into drug molecules would increase their metabolic stability [20], by avoiding, e.g., fast oxidation by cytochrome P450 oxidases [21]. In particular, the introduction of a trifluoromethyl group (–CF3) was shown to increase the metabolic stability of molecules

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• trifluoromethyl groups [20] and the cross-coupling of aryl halides [21]. Like phosphonium salts in general are used as catalysts [22][23], phosphonium salts based on ortho-hydroxy-substituted phosphines received particular attention because of their zwitterionic nature and have been used as catalysts in the

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• the robustness of this method. Substrates with multiple electron-withdrawing substituents such as trifluoromethyl and bromide gave good yields. The ethyl carbamate 2q proved to be a valid substrate for the reaction with a 74% yield. Phenylacetamide as the substrate resulted in the formation of 2r in

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• were between 7–18%. Synthesis of tripyrrane 5 5,10-Bis(4-trifluoromethylphenyl)tripyrromethane (5) was obtained as side product of dipyrromethane synthesis by the condensation of pyrrole and 4-(trifluoromethyl)benzaldehyde. A typical procedure involves 4-(trifluoromethyl)benzaldehyde (28.7 mmol) and

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• organofluorine compounds has become a major research focus. The use of difluoromethylating and trifluoromethylating reagents is a popular approach applied to prepare di/trifluoromethyl-containing molecules [8][9][10][11][12][13][14][15][16][17][18]. Also the reaction of diverse di/trifluoromethyl-containing

• building blocks offers another mainstream approach to introducing fluorine. Among these, di/trifluorodiazoethane [19][20][21][22], trifluoromethyl aldimines [23][24][25], trifluoroacetimidoyl halides [26], and fluoroalkyl N-sulfonyl hydrazones [27] have emerged as powerful nitrogen-containing fluorinated

• the synthesis of diverse di/trifluoromethyl-containing molecules by using di/trifluoromethylated hydrazones, acylhydrazones, and their related compounds. Review Trifluoroacetaldehyde hydrazones Hydrazones possess diverse biological and pharmacological properties and have been employed in the treatment

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• copolymer, benzodithiophene-thiadiazolo-quinoxaline (Qx54), by introducing trifluoromethyl groups to the Qx moiety (Qx55). This strategic modification changed the HOMO and LUMO levels, resulting in a conversion from ambipolar charge transport to n-type charge transport. The polymeric thin-film transistors

• , based on 6-(trifluoromethyl)quinoxaline or 6-cyanoquinoxaline acceptors, respectively. The small energy splitting values (0.03–0.04 eV) and long fluorescence lifetimes (5.0 μs) indicated efficient TADF processes. The utilization of these emitters in full-TADF white OLEDs, along with a sky-blue emitter

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

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• generated via an azide–alkyne cycloaddition or a multicomponent reaction between carbonyls and azides [17]. α-Trifluoromethyl (α-CF3) carbonyls were recently utilized to generate NH-1,2,3-triazoles and fully substituted 1,2,3-triazoles [28][29]. However, there are no reports of a formal [3 + 2

• -withdrawing group, such as trifluoromethyl (4h), was obtained in 44% yield. When morpholine was replaced with piperidine (5a) or seven-membered azepane (5b) as a solvent, a decreased yield was observed (30–42%). The addition of piperidine offers an advantage in expanding the substrate scope to medicinal