Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• pyrophosphorylation had no positive effect. In the case of no observable reactivity for substrate 13, likely protonation of the amine would result in unfavourable positive charge within the active site and the absence of vital H-bond contacts. X-ray crystallographic data of a related Man-PP from T. maritima show

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• charge, can then efficiently bind molecular oxygen (step 3), leading to dioxygen adduct D. Transfer of an additional electron from a reducing partner such as cytochrome P450 reductase (step 4) generates peroxo intermediate E, which upon protonation (step 5) gives hydroperoxo intermediate F, also called

Thermally activated delayed fluorescence (TADF) emitters: sensing and boosting spin-flipping by aggregation

• Ashish Kumar Mazumdar,
• Gyana Prakash Nanda,
• Nisha Yadav,
• Upasana Deori,
• Upasha Acharyya,
• Bahadur Sk and
• Pachaiyappan Rajamalli

Beilstein J. Org. Chem. 2022, 18, 1177–1187, doi:10.3762/bjoc.18.122

• disruption of the molecular conjugation or ICT interactions upon protonation or deprotonation would lead to switching of the optical properties. While there are many reports on acid–based sensors, TADF emitter-based sensors are rare in the literature. In this context, we chose the D–A molecular design to

• acidic solution on the optical properties, we carried out the same experiment in toluene solution (Figure 6b and Figure 6d). The protonation of the pyridinyl nitrogen atom upon addition of TFA quenched the fluorescence of both compounds (Figure 6b and Figure 6d). In turn, neutralization of the toluene

• quenching and recovery were obtained for both compounds upon addition of acid and base. Thereby, the protonation–deprotonation events were confirmed using absorption spectroscopy (Figure S6, Supporting Information File 1). The new peak at λabs = 425 nm in the absorption spectrum of BPy-pTC upon adding TFA

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

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

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• thermodynamic stability (1.3:1, see Supporting Information File 1). Notably, the coordination to the Lewis acid increases the regioselectivity of protonation in the allylic anions formed in the electrolysis. Thus, using LiCl as a supporting electrolyte increases the ratio to 5:1. An even more pronounced effect

• nucleophilic functionalization of the double bond of the dehydroalanine derivatives formed after the reductive ring opening and subsequent protonation. Such an approach opens a route to double functionalization of the amino acids side chain. Insertion of the sulfur-containing fragments is of special interest

• as described above (two-compartment cell, DMF, Bu4NBF4, a glassy carbon WE, an iron wire as a CE). After 2 F/mol amount of electricity passed and subsequent protonation with PhNEt2·HCl, aryl- or benzylthiol was added. The reaction mixture was kept overnight and then the products were isolated using

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• ). Mechanistically, the arylation of diazo substrates 10 likely proceeds via the protonation of the diazo moiety and elimination of a nitrogen molecule, whereby carbocation 17 is generated. The latter can either be deprotonated to give byproduct 15 or be intercepted by an arene molecule in SEAr fashion to give

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

• from the corresponding vic-1,2-diol. Water may play a role as a proton source to facilitate the formation of the protonated ketyl radical through a concerted proton-electron transfer toward the ketone or smooth protonation of the radical anion species, which readily dimerize to vic-1,2-diol 2a [46][49

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• -deficient alkyne resulted in adduct B. Thirdly, the intramolecular addition of the carbanion to the carbonyl group afforded species C, which in turn converted to the final product 3 by the protonation of the species C. The protonated species 5 could be successfully isolated in 12% yield after six hours when

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• (Table 1, entry 4). However, using a silver electrode the corresponding thione was not observed (Table 1, entry 3) [37]. In view of the acidic character of the perfluorosulfonic acid Nafion® membrane, and possible NHC protonation to form the imidazolium cation, the Nafion® membrane was pretreated with an

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• any free energy barrier. The deprotonation and re-protonation steps are not included in our calculations. The overall exergonicity of this process which transforms four π-bonds to σ-bonds, with accompanying gains in intramolecular dispersion interactions, is −62.8 kcal/mol. IE pathway As described

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• -dimethylcyclopropyl unit [28]. Bicyclogermacrene (B) served as the branch point of aromadendrane cyclization and aristolane cyclization routes (Scheme 1, I). On one hand, the protonation on the double bond Δ1,10 of B initialized the aromadendrane cyclization, followed by 1,5-bond formation to yield carbocation

• ], which was further oxidized to afford 2. On the other hand, the aristolane cyclization route is started from protonation on Δ4,5 of B and followed by 5,10-cyclization to give maaliane-type carbocation intermediate F. Then, a successive transformation involving the concerted 1,2-hydride and 1,2-methyl

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• performed a detailed investigation on the dearomatizing anionic cyclization of diphenyl-N-alkyl-N-benzylphosphinamides 107, 116, and 119 by treatment with sec-butyllithium and protonation with various alcohols (MeOH, iPrOH, t-BuOH), phenols (PhOH, 2-tert-butyl-4-methylphenol, and 2,6-di(tert-butyl)-4

• intramolecular nucleophilic dearomatization and protonation or electrophilic alkylation reactions, affording the corresponding dihydronaphthylene-fused γ-phosphinolactams 135–142. Methanol was used as the electrophile for protonation, while methyl iodide and allyl bromide were used as electrophiles for

• steric methanol as the electrophile because the protonation occurred at both the α- and γ-positions of the phenyl group in their diphenylphosphinamide moieties. However, only one pair of meso-bis(cyclohexadiene-fused γ-phosphinolactam)s 192 as major products and one pair of racemic diastereomeric bis

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• , the radical intermediate C is further reduced to generate anion D followed by protonation to give products 4 and 6. Conclusion We have successfully carried out catalytic electrochemical reduction of bromodifluoromethyl phenyl sulfide using o-phthalonitrile as mediator to generate (phenythio

Palladium-catalyzed solid-state borylation of aryl halides using mechanochemistry

• Koji Kubota,
• Emiru Baba,
• Tamae Seo,
• Tatsuo Ishiyama and
• Hajime Ito

Beilstein J. Org. Chem. 2022, 18, 855–862, doi:10.3762/bjoc.18.86

• various phosphine ligands [62] for this reaction (Table 1, entries 1–8). Interestingly, we found that tri-tert-butylphosphonium tetrafluoroborate (t-Bu3P·HBF4) provided the borylation product 3a in excellent yield (92%, Table 1, entry 1), with a small amount of the protonation product 4a (5%, entry 1

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• . In 2002, Monkman reported the addition of camphor sulfonic acid (CSA) to the fluorescent polymer poly{2,5-pyridylene-co-1,4-[2,5-bis(2-ethylhexyloxy)]phenylene} (compound 1 in Figure 2) containing pyridine groups led to the protonation effect [26]. CSA has strong acidity and low volatility, which is

• feasible to be bound with pyridine groups. As shown in Figure 3a, the protonation by CSA resulted in a significant red-shift in the photoluminescence (PL) spectrum, which was similar to the cases caused by other Lewis acids such as methanesulfonic acid (MSA) and dichloracetic acid (DCA). Wang et al. used

• light, which confirmed that the emission was sensitive to BF3 concentration. Yang et al. used also TFA to shape the fluorescence emission based on the protonation effect between the dissociated H+ and the fluorescent material [32]. Lin et al. used the Lewis acids B(C6F5)3 and AlCl3 to regulate the

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• during protonation of Ruhemann's purple. Although there was conclusive evidence of the structure of PRP (1) in the Grigg's study (proven by X-ray analysis) [27], we aimed to establish a stability order of tautomers on the basis of calculated relative values of the Gibbs free energy. Upon treatment of

• Ruhemann's purple with hydrochloric acid, three tautomers 1, 1', and 1'' may be theoretically formed, i.e., protonation could occur at the nitrogen atom, the oxygen atom or the carbon atom, respectively (Scheme 7). According to literature data [27], the nitrogen atom of Ruhemann's purple is considered to be

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