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

• )] (k298 = 32.2 kHz) move across the deck 82 and prevent binding of the protonated DABCO at the ZnPor binding sites. Use of the fuel acid 112 or 113 instead of applying the TFA/DBU acid/base combination leads initially to protonation of DABCO but due to the decarboxylation of 114 the resulting strong base

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• completely quenched by the addition of an 0.1 M HCl solution to solutions of compounds 4a and 4e (Figure 3). This result indicated that the protonation of the secondary amine disrupted the intermolecular π–π interactions or planarity of compounds 4 (Figure 4), and the rigid structure in solution was involved

• fractions. Fluorescence spectral changes of (a) 4a (10−5 M, Exmax = 413 nm) and (b) 4e (10−5 M, Exmax = 415 nm) upon addition of 0.1 M HCl. Protonation of N-methyl-4-((pyridin-2-yl)amino)-substituted maleimides 4 by 0.1 M HCl. Frontier molecular orbitals and HOMO–LUMO energy gaps of compounds 3a, 4a, and 4e

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• leading to intermediate A, nucleophilic attack of phenolate at the less sterically hindered carbon of the above zwitterion A and subsequent protonation of anion B (Scheme 8). Based on these plausible mechanisms for the formation of phenoxyketones, it can be assumed that a decline of the Cs+ concentration

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• promoting the protonation of the substrates leading to the formation of cationic intermediates that are stabilized within the cavity with consequent peculiar features in terms of acceleration and product selectivity. In all cases the catalytic activity displayed by the hexameric capsule is remarkable if

• all these reactions is the combination of its weak Brønsted acidity [42] that, by protonation of the substrate, leads to the formation of cationic species [43] and the stabilization of the latter through cation–π interactions [44] within the electron-rich aromatic cavity of the capsule, thus providing

• selectivity towards isopulegol with increasing the volume of the cavity. As a further investigation concerning other possible isomerization reactions involving protonation of the substrate, and formation of possible cationic intermediate species, we tested the menthone isomerization to isomenthone [53

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

• 18 via a concerted protonation and C–C bond formation. Weakened dispersive interactions caused by a substituent or heteroatom resulted in low yields and reduced regioselectivities. In 2020, Li and Van der Eycken and co-workers reported the synthesis of densely functionalized, polycyclic azepino[5,4,3

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• cheap and simple acid enables a temporary protonation while time-controlled decarboxylation liberates volatile CO2 and chloroform as single waste (Scheme 2a). This strategy has been applied with success by the groups of Takata, Leigh, Kim and ours to time control different molecular switches ranging

• equilibrium supramolecular machinery through a temporary protonation returning to the initial state upon time [3][4][5]. While conceptually interesting, in terms of laboratory practicability, it would be desirable to have a faster release of the free amine. For this purpose, a small amount of volatile base

• yield (Scheme 3). This highlights the potential of this technique for organic synthesis. Conclusion To conclude, we have disclosed a new approach considerably limiting waste and operations necessary for amine purification. Taking advantage of a temporary protonation with TCA, the solid amine salts

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• afforded the same major diastereoisomer but opposite enantiomers (Scheme 3, 3q). The diastereoselectivities were similar for the isomers. Since the diastereoselectivity of the reaction was low, we attempted to increase the ratio of diastereoisomers via enolisation followed by diastereoselective protonation

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• reactivated by protonation for further cyclisation steps, while previously discussed intra- and intermolecular hydrogen transfers are not supported. Furthermore, the isolation of the new natural product (2S,3S,7S,10R)-guaia-1,11-dien-10-ol from patchouli oil is reported. Keywords: biosynthesis; DFT

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

• Fürstner [62] and Plietker [63] showed iron catalysts were able to ring-open vinylcyclopropanes for monocarbofunctionalization terminating in protonation; however, Gutierrez demonstrated the resultant radical could undergo Fe-catalyzed cross-coupling reactions. The authors noted the reaction was tolerable

• synthesis of 3‐silylspiro[4,5]trienones 93 in good yield (Scheme 17) [95]. Compared to previously reported inter-/intramolecular CDC cascades, the authors were able to capture the post-cyclization aryl radical with the peroxide initiator rather than simply terminating the reaction with protonation. In terms

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

• -promoted steps, beginning with a vinylogous α-ketol rearrangement to 46. Following protonation of the enolate and addition of hydroxide to the carbonyl on the D ring, 47 rearranges with loss of chloride to give enedione 48. Base-catalyzed isomerization yields 44, which is apparently more stable despite the

• , ring strain, or α-carbonyl group), α-iminols are typically less stable than their α-amino ketone products. In the presence of a Brønsted acid, protonation of the amine product can be used to drive the rearrangement to completion. Thus, favorable yields and stereoselectivities can be realized by first

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

• . Nonetheless, use of the weaker acids seems to be crucial, since with strong acids the protonation to 20 appears not to be reversible, and direct cyclization of 20 to 19a cannot be occurring (cf. Table 1, entries 6–21). Secondly, the acid is also likely to facilitate enolization of the ester such that 5-exo

• appeared that, even in acetic acid at room temperature, protonation of 25a was virtually instantaneous and irreversible, as evinced by the formation of a baseline spot for the acetate salt. Since the analogous five-membered enaminones 15 form an obvious baseline salt spot only with strong protic acids but

• not with acetic acid, it appears that protonation of the pyrrolidine-based enaminones with this weak acid must be readily reversible. Thus the critical isomerization equilibrium postulated to be essential for pyrrolizine formation (see Scheme 3) appears not to operate to any appreciable extent with

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

• standard conditions. The proposed catalytic cycle included aza-Michael addition of arylamines, Lewis acid copper(II)-catalyzed intramolecular 5-endo-dig cyclization, protonation, and oxidation to provide the final products, tetrasubstituted pyrroles 39. The introduction of a trifluoromethyl group into

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• ], it was shown by means of NMR spectroscopy and DFT calculation that the protonation of these oxadiazoles in Brønsted superacids TfOH and FSO3H gave reactive N,C-diprotonated species. The protonation of oxadiazoles 1 takes place at the nitrogen N4 and the α-carbon of the side chain C=C bond. One would

• expect the formation of similar dications at the protonation of acetylenyloxadiazoles 3 in Brønsted superacids (see Table 1). Table 1 contains data on DFT calculations of cations Aa–d (N-protonated forms) and Ba–d (N,C-diprotonated forms) derived at the protonation of oxadiazoles 3a–d. Charge

• delocalization, contribution of atomic orbital into LUMO, global electrophilicity indices ω [26][27], and Gibbs free energies of protonation reactions with hydroxonium ion (H3O+) ΔG298 were calculated. Big negative values of ΔG298 (−86.6 to −79.2 kJ/mol) of the first protonation step show that the formation of N

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• derivative 127. The plausible mechanism for the formation of compound 127 proceeded consecutively with π-complex formation, Friedel–Crafts type addition, deprotonation, and finally protonation of alcohol for the elimination of water to get the final product [92]. A Hg(OTf)2-mediated cyclization was utilized

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

• -3-yl) phosphate 2 is activated by protonation with a haloid acid. Subsequently the phosphate leaving group is eliminated to generate the carbocation intermediate III, which is then followed by rapid combination with a nucleophilic halide ion to form a 3-monohalooxindoles 3 or 4. Conclusion In

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• example utilizing this strategy was provided by Jacobsen and co-workers for the desymmetrization of meso-aziridines 29. In their work, the bifunctional phosphinothiourea catalyst 31 promoted the C–N bond cleavage by hydrochloric acid upon initial protonation (Scheme 7) [55]. Subsequently, the catalyst

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• -polyazulene 5 (417 nm) compared to azulene (1, 341 nm) supporting the presence of extended conjugation prevailing in the polymer. The absorption and EPR spectral patterns of 1,3-polyazulene 5 recorded in TFA and H2SO4 were contrasting to each other inferring the varied degree of protonation caused by these

• acids on the polymer backbone. The direct current (DC) conductivity of protonated and iodine-doped 1,3-polyazulene 5 (0.74 and 1.22 S/cm respectively) was significantly higher than its neutral form (<10−11 S/cm). The increased conductivity of 1,3-polyazulene 5 upon protonation can be attributed to the

• protonation of 17 and 18 by TFA resulted in a large red-shifted broad absorption band in the 500–900 nm region due to the formation of azulenium cations in the polymer backbone unlike the 1,3-polyazulene 5, which had no significant effect on its absorption spectrum upon protonation. The HOMO–LUMO gap for the

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• effect of the 2-SO3H substituent formed by the protonation of the sulfonate anion in 18-2h. 1-19. 1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane salts (NFTh) In 1995, Poss and Shia disclosed the synthesis and fluorination reactivity of 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• ). Manganaelectro-catalyzed late-stage azidation of bioactive molecules. Mn-catalyzed late-stage amination of bioactive molecules. a3 Å MS were used. Protonation with HBF4⋅OEt2 (1.1 equiv) in dichloromethane before amination, then deprotonation with 1 M NaOH in dichloromethane after amination. b3.0 equiv of PhI

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• , in this case, the activity of the catalyst is not rate determining. This observation is rationalized by the occurrence of a non-productive acid–base equilibrium involving the de- and re-protonation of the considerably acidic alkyne proton in d (pKa = 15.61 [20]) [21]. The reaction conditions

• and -donor and the corresponding zwitterion i is believed to be decisive for the efficacy of the subsequent reaction, protonation of i by the alcohol resulting in the formation of ion pair ii (Scheme 1) [40]. In turn, the pKa value of the alcohol is another important parameter for the speed of the

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• -bonding (Figure 6) [94]. A significant bottleneck for triple helix formation is the requirement for cytosine protonation to form the natural C+•G–C triplet. Because of the low pKa of cytosine (≈4.5), formation of the C+•G–C triplet is unfavorable at physiological pH, which severely destabilizes the

• pseudoisocytosine (J, Figure 6) in triplex-forming oligonucleotides, alleviating the problem of unfavorable cytosine protonation [95][96]. Nielsen and co-workers replaced Cs with Js in the Hoogsteen strand of their original design of bis-PNAs in 1995 [34]. While J demonstrated weaker binding than C at pH 5, J

• cationic RNA binding compounds, perhaps, because the protonation event is coupled with the Hoogsteen hydrogen bond formation. As a result, the partially protonated M strengthens the triple helix without compromising the sequence specificity of recognition [28][30][31]. As discussed above, guanidine groups

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

• the protonation of a Pd(II) enolate intermediate by a proton source (HCl) generated at the cyclization step. The catalytic cycle begins with the enolic carbon of A attacking the complexed metal–olefin double bond in a turnover-limiting 6-endo-trig cyclization step (Scheme 3). The formed alkylpalladium

• (II) intermediate (B) then undergoes a sequence of reversible hydride β-eliminations [30] until the formation of the Pd(II) enolate (F), which, after protonation, irreversibly furnishes the product 2 and regenerates the Pd(II) catalyst. The lack of the usually kinetically favored 5-exo-trig

• product was also compatible with the reaction conditions. Alkylated phenols 61 were obtained after protonation/isomerization of the generated enolate intermediate (Scheme 24B). In 2018, the same authors continued to explore the synthetic opportunities offered by the enolate generated in MHAT radical

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• , protonation might not be the key step, and the highly oxidizing nature of nitration conditions that can lead to the formation of a cationic intermediate via a radical cation might control this reaction [68]. A possible mechanism for the formation of 5 and 6 starts with protonation of 1 give the Wheland

• observed (Figure 6). As with the oxidation, we assume that the lower deck blocks approach from one face. Protonation of the adduct also occurs anti to the para ring. We suspect that this second addition favors the trans product over the cis rather than the para ring influencing the approach of the proton

One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)

• Louis G. Mueller,
• Allen Chao,
• Embarek AlWedi and
• Fraser F. Fleming

Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106

• in 93% yield (Table 1, entry 6). Presumably the cyclization of 6 is followed by protonation at the former isocyanide carbon by HMDS (the emerging C-2 of the imidazole) with the reformed LiHMDS deprotonating C-4 to form the imidazole ring. Identifying LiHMDS as the optimal base allowed the scope of

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• in determining ring closure either via path a or path b. In path a, the protonation of the imine nitrogen in 7a by the conjugate acid (+ BH) leads to an electrophilic aromatic substitution at the 3-position of the indole unit to form a carbon–carbon bond in the intermediate 8. A further proton

• moderately polar dichloromethane and then highly polar DMSO (Table 2, Figure 3). The fluorescence quenching of 3ac in methanol is attributed to the partial protonation of the carboline unit's nitrogen atoms facilitated by polar-protic solvents [33]. The fluorescence lifetimes were measured by time-correlated