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

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

• observed. The efficiency of the reaction seems to be dependent on the deprotonation of the α-position of the olefinic malonate species. The authors noted decarbonylated products were obtained when cyclohexane carboxaldehyde and pivaldehyde were applied, consistent with the stability of the generated acyl

• radical intermediate 137. Subsequently, intramolecular cyclization of 137 generates radical intermediate 138 which then successively undergoes a SET of Fe(III) and deprotonation by t-BuO− to give the annulated product 133a and regenerates the Fe(II) active catalyst. In 2014, the Loh group reported an

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

• similarity in reaction, 1-deoxy-ᴅ-xylulose-5-phosphate reductoisomerase (DXR) instead uses a retro-aldol/aldol sequence to accomplish its rearrangement of 68 to 69. c) The secondary metabolite aurachin C (71) is oxidized by the FAD-dependent monooxygenase AuaG to epoxide 72, which upon deprotonation by an

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• cation I and a CuI species. This process regenerated CuII in the presence of molecular oxygen. The deprotonation of the nitrogen radical cation produces an α–amino radical II, which was further oxidized to the iminium ion III to which the copper alkynylide added forming the desired product (Scheme 17

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• allylic functionalization of 2-alkylazaarenes. Due to the high pKa value of alkyl azaarenes, the functionalization of benzylic C(sp3)–H was challengeable and pre-activation of the benzylic proton with suitable Lewis acids was often required prior to deprotonation of the alkyl chain by a stoichiometric

• MBH-derived allyl bromides (Scheme 1d) [30]. This reaction was assumed to involve the deprotonation of the initially formed 2-methylpyridinium salt by base to generate an N-allyl enamine intermediate, which undergoes a 3-aza-Cope rearrangement to give the allyl-substituted products. To the best of our

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

• intramolecular nucleophilic attack by azide and the following deprotonation by a fluoride anion provide the final product 8 (Scheme 5). The derivatization of sulfonated aminonicotinates 8 could easily be achieved. Desulfonylation of aminonicotinate 8b proceeded smoothly in the presence of triflic acid (2.0 equiv

• generate intermediate 20. Then, the intramolecular nucleophilic attack by azide and the following deprotonation give the final product 18 or 19, respectively. 5‑Selenyl- and 5-sulfenyl-substituted nicotinates can carry out versatile transformations, which have potential application in pharmaceutical

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• attack at (R)-A to form (R)-9, while the distance to the cation in (S)-A is too large, preventing its attack to form (S)-9. In contrast, the formation of 8 only requires deprotonation that seems to be possible for both intermediates (R)- and (S)-A, explaining why compound 8 is nearly racemic. As the

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• anti-addition of the sulfoxonium ylide to 52. Hou highlighted that the good diastereoselectivity control for the sulfoxonium ylide addition to acyclic α,β-unsaturated substrates such as 52 observed in their work represented the first example in literature. Hereupon, deprotonation of 53 over LiHMDS

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

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• to the ability of squaramides to bind anionic species more strongly than ureas. The moderate enantiocontrol observed thus far prompted us to posit that the nitrogen atom on the quinoline moiety of the catalyst could participate to the deprotonation of 5a, therefore, leading to less selective

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• were found to be suitable to achieve the transformation in satisfactory yields under visible light irradiation (Scheme 2). The authors hypothesized that the key α-nitrogen carbon-centered radical 5 could be generated via a photoredox-driven N-phenyl oxidation and α-C–H deprotonation sequence from

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• receptor potential channels such as TRPM-7 [35]. In 2015, Murakami synthesized the novel indole C-2 borinic acid derivative 3 by reacting N-methylindole (1) with triisopropyl borate (2) in a strongly basic medium (Scheme 1). The product formation proceeds through the indole C-2 deprotonation mechanism [36

• excess of the indole reactant. It is seen that in the presence of a base the C-2 deprotonation becomes very fast in 9 (for regaining aromaticity) so the boron at the initial C-3-borylated intermediate 8 (formed via SEAr) cannot migrate fast enough, leading to a C-3 borylation product 10a (unlike Pd) [38

• ][39][40]. Here the absence of the base resulted in a slow or no C-2 deprotonation of 9, which in turn forces the boron to migrate to C-2 from C-3 (8, Scheme 2b) to result in the C-2 borylation (10b). Amines Bis(indolyl)amines have recently become important as organic electroluminescent materials [41

Preparation of mono-substituted malonic acid half oxyesters (SMAHOs)

• Tania Xavier,
• Sylvie Condon,
• Christophe Pichon,
• Erwan Le Gall and
• Marc Presset

Beilstein J. Org. Chem. 2021, 17, 2085–2094, doi:10.3762/bjoc.17.135

• affords the advantage of being based on commercially available malonates. We thus envisioned to achieve the alkylation step by deprotonation of a malonate with NaH followed by treatment with a halogenated compound. As our first attempts revealed a strong influence of the stoichiometry and the nature of

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• -bifunctional organomagnesium alkoxide reagent 107, which converted esters into di- and monofunctionalized anthracenes (Scheme 25) [59]. They prepared this reagent by deprotonation–magnesiation of compound 106. Then, the treatment of aromatic esters with 107 produced dialkoxide 108, which could be easily