Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as an additive. These results provide fundamental insights for the design of PCET-based redox reaction systems under electrochemical conditions. Keywords: amidyl radical; cyclic voltammetry; electrosynthesis; hydroamination; proton coupled electron transfer

• of conjugate addition of a cathodically generated carbamate anion was ruled out, prompting us to consider that N-alkylation proceeded via a radical mechanism. On the other hand, the addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) led to the predominant formation of cyclized dimer 4 without N

• wave was observed at approximately +1.4 V (Figure 2A). The oxidation current of this wave decreased significantly in the presence of a phosphate base and the subsequent addition of HFIP enhanced this phenomenon (Figure 2B, grey line). In contrast, using AcOH instead of HFIP did not affect the oxidation

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• . Thus, aiming at enhancing the catalytic activity, we performed some additional photocatalytic tests, upon the addition of different concentrations of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). This alcohol has interesting physical and chemical properties, and, being well miscible with many organic

• %, 2%, and 5% of HFIP (see Table 4). The concentrations of the main components were: [1] = 5 μM, [PS] = 0.5 mM, and [BIH] = 10 mM. After four hours of irradiation at 420 nm, the production of CO increased remarkably, reaching a TON higher than 230 when 5% HFIP were used (Table 4, entry 3

• ). Unfortunately, also the generation of H2 increased with the concentration of HFIP, lowering the selectivity to 55%. Nevertheless, these results are promising, and further optimization studies are necessary to achieve high efficiencies and selectivity at the same time. Conclusion We presented a novel Co(II

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• K. HFIP was supplemented with 3 g/L potassium triflate, and the flow rate was adjusted to 0.50 mL/min. Calibration was performed using PEG standards with molar masses ranging from 0.1–1,000 kg/mol. Before every measurement, samples were filtered through 0.2 µm PTFE filters, Roth (Karlsruhe, Germany

• -oxazoline ring-opening polymerization. Circles with red fringes were excluded during the linear fit. (b) HFIP SEC traces of the resulting poly(2-ethyl-2-oxazoline)s obtained at 60 °C. Investigation of 2-ethyl-2-oxazoline polymerization initiated with EtOxMeOTf at different monomer/initiator ratios. (a

• ) Dependence of the apparent polymerization constant on the chain length, calculated from the first-order kinetic plot for the cationic ring-opening polymerization of 2-ethyl-2-oxazoline initiated by EtOxMeOTf in DLG at 60 °C and (b) HFIP SEC traces of the resulting poly(2-ethyl-2-oxazoline)s. Investigation of

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• yields (40–46%, Table 1, entries 2 and 3). By exchanging TFE for the more stabilizing 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) it was possible to increase the yield even further to 78% (Table 1, entry 4) [43][44]. Finally, we decreased the amount of TfOH to 2 equiv still yielding product 1a in 76% yield

• (Table 1, entry 5). After establishing the optimized reaction conditions for batch, we wanted to find conditions for a flow procedure. It was observed that plastic parts made out of PEEK did not tolerate the acidic conditions in HFIP, and the solvent was changed back to TFE. This worked surprisingly well

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• lutidine base, 7 mol % organic photocatalyst 4CzIPN, 30 mol % NiBr2, and 30 mol % bpy provided 57% of 9. Intramolecular Friedel–Crafts reaction by Et2AlCl and HFIP complex led to 123, possessing the correct connectivity for the divergent synthesis of the family. Choreographically executed sequential

• the erythrinadienone intermediate 182. On contrary, common scaffold 180 should hydrolyze to sebiferine-type scaffolds in the presence of water. Taking these results into account, the group exploited the ability of HFIP to stabilize the radical cation formed by PIFA and BF3·EtO2 [95][96] to selectively

• used. The first one was loaded with the substrate and the second with PIFA and BF3·EtO2, while HFIP was used as the solvent. The two streams were mixed in a T-mixer, equipped with a 250 μL frit, to ensure efficient mixing. Under the optimized conditions, the method provided aporphine products in good

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• ) or aromatic aldehydes [79] (in 1,1,1,3,3,3-hexafluoropropan-2-ol, HFIP) at room temperature. The selectivity of aldehyde formation without the overoxidation to the carboxylic acid was explained by an inactivation of the aldehyde to further oxidation via the hydrogen bonding between the aldehyde and

• HFIP. The regioselective amination of benzylic positions in alkylarenes [82] and ethers [83] directed by steric effects was achieved by the development of sterically hindered “bowl-shaped” imide-N-oxyl radical precursors (Scheme 7). The presented example with a sterically hindered N-hydroxyimide

• oxaziridinium organocatalysis was developed recently [138]. The advantage of this method is the compatibility with secondary alcohol groups, which are not oxidized and can be used as a directing moiety. The use of HFIP as a strong hydrogen bond donor solvent protecting alcohols from oxidation was considered as

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• catalyst-free methods, the use of costly and low boiling hexafluoroisopropanol (HFIP) as solvent offered the para-selective halogenation of activated aromatic systems (Scheme 1c) [44]. It is noteworthy to mention that over-halogenation of activated systems like phenols and anilines, due to the high

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• )ruthenium(II) dichloride as catalyst. Then, a BF3·OEt2-catalzyed migration of the methyl group to the C-2 position and removal of the tert-butoxy group in a 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)/toluene mixture afforded 2-methyl-1,4-benzoquinone (29). Finally, a Diels–Alder reaction was performed with

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• regioselectivity switching in the SEAr-based cyclizations of 3,5-unsubstituted, 4-substituted indoles. In the course of their studies on chemospecific cyclization of α-carbonyl sulfoxonium ylides on aryls and heteroaryls, the Aïssa group in 2019 demonstrated hexafluoroisopropanol (HFIP)-promoted regioselective

• cyclopropanes, Li and co-workers treated compound 36 with triflic acid (TfOH) in refluxing HFIP (Scheme 13) [24]. The reaction afforded compound 37 in 82% through the regioselective intramolecular ring-opening of the cyclopropane ring at the benzylic carbon atom. Very recently, our group has reported the

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• TFE replaced by the even more electrophilic 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) component. The 97% TFE has a YCl value (for interaction at chlorine) of 2.83, which increases to 5.08 on going to 97% HFIP [25], corresponding to a considerable increase in its ability to interact with, and assist in

• is the value in 80% ethanol (20% water) and k is the value of the specific rate of solvolysis in another solvent of interest. If a given solvolysis, such as of an alkyl chloride, is studied over a wide range of solvent types such as from ethanol (NT = 0.37; YCl = −2.52 to 97% HFIP (1,1,1,3,3,3

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• copper salts such as Cu(acac)2 (Table 1, entry 7), Cu(TFA)2, (Table 1, entry 8), Cu(OAc)2 (Table 1, entry 9) and replacing TFE with other protic additives including MeOH (Table 1, entry 10), EtOH (Table 1, entry 11), HFIP (Table 1, entry 12) and H2O (Table 1, entry 13). The scope of the continuous-flow

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

• -arylnitroolefins 101 and the best results (yield 99%, ee 91%) were obtained in the reaction of benzylamine (R1 = Ph) on using the NHC precursor as shown below in the presence of hexafluoroisopropanol (HFIP) as additive along with molecular sieves (4 Å) (Table 23) [63]. The role of HFIP is to act as proton shuttle

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• reaction was observed in its absence. The authors highlighted the role of the solvent hexafluoro-2-propanol (HFIP) in the stabilization of the radical cation induced by PET and its assistance in the hydrogen shift process. Miscellaneous Lewis acid catalysis in olefin hydroalkylation reactions The ability

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• proton source and the observed reduction of Pd(II) to Pd(0). HFIP was used as a proton source instead and Pd(0) was reoxidised to Pd(II) by p-chloranil between the individual cycles. The ratio PS-PyOx:Pd(TFA)2 showed a crucial role in the enantioselectivity. Using a higher excess of PS-PyOx allowed

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• bisacetal precursors, which were readily prepared through C–C bond formation by Suzuki–Miyaura coupling. This cyclization was efficiently realized by a catalytic amount of trifluoromethanesulfonic acid (TfOH) in a cation-stabilizing solvent, 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), which readily allowed

• metal catalysts. Recently, we have developed a Brønsted acid-catalyzed cycloaromatization in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as solvent [20][21][22]. Fluoroalcohols, such as HFIP, exhibit high ionization power and low nucleophilicity, based on the electron-withdrawing inductive effect of

• fluorine, which helps to generate cations but does not affect cationic reactions [23][24][25][26][27]. Thus, HFIP greatly facilitates reactions via cationic intermediates [28]. In the presence of a catalytic amount of trifluoromethanesulfonic acid in HFIP, (biaryl-2-yl)acetoaldehydes or their acetal

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

• was also noticed, with the higher ratios being obtained in the most ionizing and less nucleophilic solvents (i.e., 1.34 ± 0.07 in HFIP vs 1.21 ± 0.01 in 80% EtOH). The subsequent solvolysis of enantioenriched triflate (R)-(−)-22f evidenced that in a poorly ionizing solvent, such as AcOH, solvolysis

• occurred with 41% inversion (and 59% racemization, i.e., product 23f was obtained with an enantiomeric ratio of ca. 70:30 in favor of the (S)-enantiomer), while complete racemization was observed in more ionizing TFA or HFIP as the solvent (Figure 5b) [48]. These observations are in agreement with a

• process generating a carbenium ion in highly ionizing solvents (TFA, HFIP, etc.) for the tosylates derivatives, and with the concomitant formation of a contact ion pair 25fOTf favoring the SN2 process in less ionizing solvents (Figure 5c). Recent studies conducted by Moran et al. support the ionization

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• (64% and 56% yield, respectively, Table 1, entries 2 and 4). Fluorinated solvents such as hexafluoroisopropanol (HFIP) or ethyl trifluoroacetate (ETFA) led to similar results (52% and 50% yield, respectively, Table 1, entries 5 and 6). Switching to non-halogenated solvents such as acetonitrile or

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

• )bis(thiourea) (4) were observed after stirring 12 h at room temperature (Table 1, entry 2). An increase in the yield of product 4 was observed when the reaction time was extended to 24 h (Table 1, entry 3). Changing the solvent to either hexafluoroisopropanol (HFIP) or 1,4-dioxane did not provide

Fabrication of supramolecular cyclodextrin–fullerene nonwovens by electrospinning

• Hiroaki Yoshida,
• Ken Kikuta and
• Toshiyuki Kida

Beilstein J. Org. Chem. 2019, 15, 89–95, doi:10.3762/bjoc.15.10

• its low self-assembly features in solution [15]. We recently reported that 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) is a suitable solvent for CDs, and a CD/HFIP solution can be facilely electrospun into fibers at a relatively low concentration of approximately 12.5 w/v % [11], which is comparable to

• paper, we report the successful electrospinning of native CD–fullerene inclusion complexes in a HFIP solution to produce a new type of supramolecular fiber material. An advantage of our system compared with the previous technique [10] is that only 12.5–20 w/v % CD/HFIP solution is required. This

• realizes easy handling of inclusion complexation with guest molecules as well as electrospinning due to the much lower viscosity of the CD/HFIP solution. The formation of a 2:1 inclusion complex should not affect the solution properties (e.g., viscosity and solubility), but should provide electrospinning

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• , leads to their deprotonation with a stereoselective formation of (arysulfonyl)butadienes (for instance, ArSO2–CR1=C–C(Me)=CH2, for R2 = R3 = Me, yields of 87–98%). Reactions of (arysulfonyl)allenes in the system TfOH (0.1 equiv)–HFIP (hexafluoropropan-2-ol) followed by hydrolysis give rise to allyl

• cases, these reactions were unselective. For instance, for allene 2a, mixtures of butadiene Z-3a and alcohol Z-4a were obtained. To overcome this obstacle we decided to use 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP), which was known to form the corresponding ether for further substitution reactions [33

• ]. Indeed, the use of HFIP and a catalytic amount of TfOH (0.1 equiv) followed by hydrolysis allowed to achieve an exclusive formation of allyl alcohols Z-4a,b and E-4c from allenes 2a,b,d, respectively, in high yields (Scheme 4). The most probably, this reaction proceeds through intermediate formation of

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• sulfonated mesoporous silica materials is that they are poisoned with water. To increase the hydrophobicity of them, the authors reported some solutions such as confining fluoroalkyl-chain alcohols (RFOH) inside them. A range of RFOH including trifluoroethanol (TFE), ethanol, hexafluoroisopropanol (HFIP) was

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones

• Xiaochen Du,
• Jianjun Huang,
• Anton A. Nechaev,
• Ruwei Yao,
• Jing Gong,
• Erik V. Van der Eycken,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234

• cyclizations of 7p–r required further optimization of the reaction conditions (Tables 2–4) and were complicated due the formation of regioisomeric products. After all, 2-quinolones 8p and 8q were isolated in good yields from gold-catalyzed reactions in hexafluoroisopropanol (HFIP), while 2-quinolone 8r was

• -methylpropan-2-ol or HFIP (Table 2, entries 2–4). Using the latter solvent a full conversion of 7p was achieved at 50 °C within 20 h, allowing to isolate both possible products 8p and 8p’ in 58% and 15% yields, respectively (Table 2, entry 4). It should also be stressed, that reacting 7p in chloroform at rt

• concomitantly promoted the competing alkoxylation reaction (Table 3, entries 1 and 2). Consequently, we were able to isolate and characterize the corresponding TFE-adduct 9c (Table 3, entry 2). Switching to HFIP as the solvent prevented the alkoxylation but led to an even slower reaction rate (Table 3, entries

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• . Herein, we explored a simple and facile protocol for cobalt-catalyzed picolinamide-directed alkoxylation of 1-naphthylamine derivatives with alcohols (Figure 1c). Results and Discussion Initially, N-(naphthalen-1-yl)picolinamide (1a) and hexafluoroisopropanol (HFIP, 2a) were chosen as the model

• effective and the alkoxylated product 3aa could be isolated in 82% yield. Next, the effect of oxidants on the reactivity was investigated, and Ag2CO3 showed a superior result compared with alternative oxidants (Table 1, entries 6–8). Moreover, DCE and HFIP as co-solvents demonstrated higher reactivity

• alkoxylation of arenes with primary alcohols [30][31], HFIP (2a), isopropanol (2t), isobutanol (2u), and isopentanol (2v) could all proceed smoothly to deliver the alkoxylated products in 58–89% yields. Furthermore, we attempted some tertiary alcohols (tert-butanol and 2-methyl-2-butanol). However, no desired