Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• salts 41. The latter underwent deprotonation in the presence of triethylamine in pyridine to generate the carbene intermediates 42 (Scheme 9). After that, the optically active imidazole-2-thiones 43 were obtained through the reaction with elemental sulfur. In CHCl3 solutions, the study of the optical

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• highly halogenated carbon centers, which enable halothane to participate in various reactions such as homolysis of carbon–halogen bonds and deprotonation. Multi-fluorinated compounds such as HCFC-133a (CF3CH2Cl) and HFC-134a (CF3CH2F) have been widely used in reactions with a variety of nucleophiles to

• for obtaining 1. The desired highly halogenated aryl alkenyl ether 2a was obtained, but the yield was unacceptably low (Table 1, entry 1). The low conversion is attributed to use of an insufficient amount of KOH, which was used as a base for deprotonation of the phenolic hydroxy group and acidic C–H

• bond between the bromine and chlorine atoms in 1. Extra KOH was added to improve deprotonation, but the yield of 2a was still low (Table 1, entries 2 and 3). Changing the solvent from THF to DME and increasing the temperature to 80 °C slightly improved the yield of 2a to 19% (Table 1, entry 4

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• the presence of 1.1 equiv of TEA. In this case, the base-promoted deprotonation of 3-bromooxindole (4) affords a highly nucleophilic intermediate, which undergoes Michael addition to FPD 1i, followed by intramolecular SN2 attack [39][40][41][42][43] by the oxygen of the aroyl group (Scheme 5) to give

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• employs an intramolecular proton transfer. We recently showed that a water-mediated concerted deprotonation–protonation is required for the MgMS-mediated cyclization [20]. In order to probe the mechanism underlying the cyclization of 1, we used His6-tagged TadA to carry out in vitro enzymatic reactions

• and TadA use protonation-induced C2,6 cyclization, TadA likely adopts a more asynchronous process to give a neutral intermediate 3 first followed by protonation to form 1, which is different from the highly concerted deprotonation–protonation process employed by MgMS (Scheme 1B). Further isotope

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• (Scheme 6); iodination with NIS, as previously described [29], gave lower yields. We first attempted the coupling with the terminal alkyne 19, anticipating the possibility of reducing the triple bond after coupling reaction. In agreement with literature precedents, we chose LiHMDS for deprotonation of 19

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

• completed a selective anomeric deacetylation on a gram-scale using ammonium acetate in DMF, to afford hemi-acetal 15 in good yield (80%) [11]. This was followed by phosphorylation of the anomeric position using diphenylphosphoryl chloride as the phosphorous electrophile, following deprotonation of 15 using

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

• 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

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

• available 3(2H)-isoquinolones followed by TfOH-promoted arylation. The generally high-yielding two-step sequence was shown to be applicable to a wide range of substrates. To a varying degree, the arylation step was accompanied by the elimination of the nitrogen molecule and deprotonation to furnish 3

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• to HBF4·OEt, for which the conjugate base has no nucleophilicity, improved the yield of 2 and the conversion of 1. Incidentally, this reaction medium includes a base, iPr2NEt, that would accelerate the deprotonation step in the formation of N-acyliminium ions from DMA at the anode. TFA and HBF4·OEt2

• ]. At the anode, electrochemical one-electron oxidation of the solvent, DMA, takes place selectively. Deprotonation, probably supported by iPr2NEt generated at the cathode, followed by further one-electron oxidation generates the corresponding N-acyliminium ion of DMA. Deprotonation supported by iPr2NEt

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

• base to catalyze the C–C bond formation via a Michael addition of active methylene groups [31]. Therefore, in the presence of TBAB, the bromide assisted with the deprotonation of the phenacylmalononitrile to give a carbanion intermediate A. Secondly, the nucleophilic addition of carbanion A to electron

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

• electrochemistry, NHC instability (and anodic electroactivity) prevented its cathodic generation and subsequent use as catalyst or reagent. Instead, the NHC was generated by chemical deprotonation using a strong base (DBU) and then applied in anodic esterification [30][31][32], and amidation of aromatic aldehydes

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

• diphosphate (E,E-FPP) as their linear precursor (Scheme 1). The 6,7-bond formation was triggered by eliminating the pyrophosphate group of E,E-FPP yielding a monocyclic carbocation intermediate A, followed by the 6,11-closure via deprotonation to afford bicyclogermacrene (B) containing a gem

• intermediate C. Firstly, deprotonation occurred to form the double bond Δ1,10 and led to the formation of (−)-ledene (D) [29], on which the multiple-step oxidation happened at C-2 and C-9 to generate (+)-1. Secondly, the reaction is quenched by an H2O attach at carbocation C-10 to form (+)-globulol (E) [30

• isomerized to nerolidyl diphosphate (NPP), followed by the 6,7-bond formation to generate carbocation intermediate I (Scheme 1, II) [31]. Sequential 1,3-hydride shift and 1,6-cyclization occurred to afford cadinyl cation (J). Further 1,3-hydride shift and deprotonation on J resulted in cadina-1(6),4-diene (L

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• ]. In the biosynthesis of terpentetriene, GGDP was first cyclized by a class II DTS (Cyc1) that contains a conserved DxDD motif to form terpentedienyl diphosphate (TDP) via a syn-labda-13-en-8-yl+ diphosphate intermediate (Figure 2), which, prior to deprotonation, can be followed by rearrangement to

• form the clerodane skeleton. TDP was then ionized by a class I DTS (Cyc2) that contains a conserved DDxxD motif and through a deprotonation to install a terminal double bond at the side chain [31][32]. We were unable to access the original terpentetriene producing strain of K. griseolosporeus MF730-N6

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• addition to generate the intermediate 9, which is oxidized by Cu(II) to give 10, which undergoes aromatization and deprotonation to afford the product 3a. At this stage, Cu(I) is regenerated to complete the catalytic cycle. Conclusion In summary, we have developed a convenient copper-catalyzed method for

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• -BINOL derivative (R)-12. In a subsequent work, Takata and co-workers showed that such chirality transfer can also be achieved by deprotonation/reprotonation of the ammonium station, leading to formation of the different co-conformers in a reversible fashion [55]. 2.2 Stereoselective catalysis As

• zwitterionic ammonium phosphate rotaxanes were inactive, deprotonation with LiOH led to active catalysts for this reaction. In all cases, the interlocked catalysts showed faster conversion (87–92% conversion after 7 days) than the corresponding non-interlocked mixtures of macrocycle and thread (35–78

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• 2,6-dimethylpyridine-3,5-dicarboxylate after deprotonation in the presence of the base DIPEA. Conclusion In conclusion, we have fabricated a simple and efficient supramolecular photocatalytic system based on host–guest self-assembled m-TPEWP5G donor and EsY as acceptor. Briefly, the m-TPEWP5 host and

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• catalysis relies on the deprotonation of one of the substrates, but basic conditions may limit the applicability of this methodology. A unique base-free variant of chiral phase-transfer catalytic alkylation of 2-oxindoles was developed by Connon and co-workers [23]. Pentacarboxycyclopentadienes are a unique

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• thiourea moiety with the oxygen of the nitrosobenzene. The tertiary amine, present in the catalyst acts as a base in assisting the deprotonation of the highly acidic malonamate to generate the corresponding enolate. Subsequently, a face-selective nucleophilic addition of the enolate to nitroso selective

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• , epimerization is prevented through deprotonation of amide NH bonds, as argued by Seebach for Li enolates [53][54]. Nevertheless, isoleucine was prone to epimerize under the reaction conditions due to its vicinity to proline and therewith lack of the “protecting” NH group. Since no full conversion was observed

• , entry 1). Since the reaction seemed to stop after 30–40% conversion, it was speculated that the ester enolate chelate complex formation was incomplete due to consumption of the base. For instance, deprotonation of tyrosine residues in benzyl position has been observed previously in the derivatization of

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• % yield. This is most likely due to the strongly basic conditions (NaH) needed for the attachment of the ethoxymethyl protecting group, which might lead to deprotonation at the CH2 group (C7) followed by the formation of undesired side products. Being disappointed by the inefficiency of this route with at

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• acid (4) (Scheme 4, reaction 4). A plausible reaction mechanism has been proposed based on the results of the control experiments. As shown in Scheme 5, the reaction starts with a base-promoted deprotonation of indole forming intermediate A. In the next step nucleophilic substitution between

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

• alternative biosynthetic mechanism that also starts with a cyclisation of FPP to A (Scheme 2A) [10], but then a subsequent deprotonation to 8, an important neutral intermediate in the biosynthesis of many sesquiterpenes [11], is assumed. A reprotonation-induced cyclisation leads to E that is again

• (Scheme 2B). According to the FPP biosynthesis as established by Cornforth and co-workers, these reactions should proceed with full retainment of all labellings [12]. For isolated 3 a loss of one of the three 3H atoms was reported that is explainable by the deprotonation step from E to 6 [10], but

• reported, which was explained by an unusual intramolecular deuterium transfer. Herein, the deuteron is released from (2-2H)-J in the deprotonation step to 5 (or other enzyme products losing the same hydrogen in the terminal deprotonation). Deprotonation of (2-2H)-H was suggested to produce the unknown

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• – deprotection, deprotonation and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps – deprotection and coupling – in only

• one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis

• reaction to carry out the deprotonation and Williamson ether formation reactions under basic conditions (Scheme 1) [15][16][18][23][25]. It is remarkable that the method has evolved to such a sophistication that the synthesis of (PEG)16 was achieved in nine steps without any chromatography [18][27

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• is reduced by the photocatalyst (PC−) after coordination to aryl bromide, promoting the turnover of organometallic and photoredox cycles. DABCO is regenerated via deprotonation by an inorganic base. We also investigated the mechanism operating when the reaction is performed in the absence of bicyclic