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

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• -1 alkylation of the exemplar methyl ester 9 and other appropriately C-3 substituted indazoles (19, or 21–24) (under conditions A, Table 1, entry 22) involves the initial irreversible deprotonation of the indazole in the presence of NaH to initially give indazolyl salt 65 which is in equilibrium with

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

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

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• corresponding triazole products in moderate yield (Scheme 8) [42]. The authors proposed a reaction mechanism in which the β-thioenaminone 18 tolerates deprotonation to afford anionic intermediate 21 through the tautomer 20 in the presence of a base. In the next step, the nucleophilic addition of 21 to the azide

• . Later, carboxylate-ligand-assisted C–H bond activation takes place through a concerted metalation–deprotonation transformation to produce the next intermediate. Finally, the corresponding product 142 is formed by a reductive elimination process, along with the regeneration of the active catalytic

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• in terms of a concerted metalation deprotonation (CMD) mechanism [50]. Interestingly, electron-rich alkyne 2f displayed a higher reactivity in the copper-promoted C−H activations as compared to the electron-poor analog 2h (Scheme 4b). A significant H/D scrambling was not detected in the ortho

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

• contain an adjacent electron withdrawing group (1, R1 = EWG) [13]. Installation of an electron withdrawing group adjacent to an isocyanide facilitates the deprotonation but creates weak nucleophiles 2 that are insufficiently nucleophilic to react with nitriles [14]. Described below is the use of Asmic

• , anisylsulfanylmethylisocyanide (5) [15], whose deprotonation affords a potent nucleophile that reacts directly with nitriles to provide an efficient, general approach to an array of imidazoles; Asmic is a crystalline, virtually odorless isocyanide with the advantage over related methods [16][17] in being readily prepared in

• fewer steps on at least 20 g scale [18], applicable for the synthesis of several heterocycles [19][20], and able to generate imidazoles from a broad array of nitrile and imidate electrophiles. Results and Discussion Exploratory deprotonation of Asmic (5) with BuLi followed by addition of butyronitrile

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• hydroxy group in the adducts, and β-elimination (Scheme 3a) [16]. The 1-bromovinyl p-tolyl sulfoxide 6 was prepared by the deprotonation of sulfoxide 8 with LDA followed by electrophilic bromination with 1,2-dibromo-1,1,2,2-tetrachloroethane. 1-Methoxyvinyl p-tolyl sulfoxide 7 was prepared by a Peterson

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• as a chiral auxiliary which was then removed by hydrolysis in the final step of the overall seven-step synthesis. Deprotonation of 41 using LiHMDS in THF in a primary reactor was performed at −40 °C and telescoped into a second reactor along with a stream containing the trityl-protected aldehyde, 42

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• byproduct 15 after deprotonation. Conclusion We have demonstrated the application of a heterogeneous CN-K semiconducting photocatalyst in the cyanomethylarylation of alkenes with acetonitrile utilizing a readily available NHPI ester as radical initiator. This transition metal-free protocol tolerates a broad

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• [62][63]. The first asymmetric synthesis of 2,2-dibromoaziridines 15 was achieved by performing the nucleophilic addition of the anion resulting from the deprotonation of bromoform with sodium hexamethyldisilazide (NaHMDS) to chiral N-tert-butanesulfinyl aldimines (RS)-14, at low temperature, and

• found that the reaction of different aromatic and aliphatic chiral imines (SS)-14 with the dienolate resulting from the deprotonation of bromomethyl butenolide 29 in THF at −78 °C led to a mixture of diastereomeric cis-vinylaziridines 30 and 31 with good yields in most cases. Lithium

• hexamethyldisilazide was the base of choice to perform the deprotonation, and it must be added very slowly to the reaction mixture in order to suppress self-dimerization of the butenolide [72]. The structures as well as the absolute and relative stereochemistry of reaction products 30 and 31 were also unambiguously

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• (by direct attack of a aryl oxide nucleophile or deprotonation and loss of chloride in a second carbene generation followed by a second phenoxide attack) would be substantially greater than an aryloxydifluoromethane such as 5, with milder conditions allowing us to avoid the undesired isomer 7

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• corresponding acyclic or cyclic allylic amines in very good yields (see Supporting Information File 1 for details). Their subsequent α-deprotonation by LDA followed by treatment with chlorotrimethylsilane at −78 °C [81] resulted in clean C-silylation of the corresponding enolate providing silylacetamides 8a–m

• enolate formation from 8h,i with s-BuLi, a deuterium quenching experiment with D2O was performed. Analysis by 1H NMR spectroscopy revealed 87 and 91% deuterium incorporation, respectively, indicating that a deprotonation occurred, but the epoxide opening was hampered by the combination of a sterically

• equilibrium (Table 4, entries 7 and 11 vs entries 1 and 9). Attempts to influence the diastereomeric ratio of the cyclization products by irreversible stoichiometric deprotonation of the lactams 12d,f,i by LDA at −78 °C and subsequent protonation by methanol did not lead to substantial changes of the initial

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• and noticeable productivity (TOF = 129 h−1, based on the moles of Zn) at 190°C, EG/PET 4:1, w/w and 5 wt % catalyst [237]. A mechanism was proposed analogous to that depicted in Scheme 6, but in which Zn2+ acts as Lewis acid and dimethylurea acts as base promoter for EG hydroxy deprotonation [238

Mesoionic tetrazolium-5-aminides: Synthesis, molecular and crystal structures, UV–vis spectra, and DFT calculations

• Vladislav A. Budevich,
• Sergei V. Voitekhovich,
• Alexander V. Zuraev,
• Vadim E. Matulis,
• Vitaly E. Matulis,
• Alexander S. Lyakhov,
• Ludmila S. Ivashkevich and
• Oleg A. Ivashkevich

Beilstein J. Org. Chem. 2021, 17, 385–395, doi:10.3762/bjoc.17.34

• -aminides. Results and Discussion Synthesis and chemical transformations Tetrazolium-5-aminides can be prepared by three main approaches: a) by the deprotonation of 5-aminotetrazolium salts, b) by the photochemical transformation of 5-azidotetrazolium salts, and c) by the functionalization of other aminides

• tetrazolium-5-aminide allows to displace halo- and methylsulfonyl groups, whereas 5-aminotetrazoles do not react under analogous conditions. So, we prepared the bistetrazolium salt 9 by the alkylation of aminide 8a with 1,2-dibromoethane (Scheme 2). The obtained salt 9 was subjected to deprotonation to give

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

• nonfluorinated analogues (Eox (PhNMe2) = +0.71 V (SCE)), the radical cation 180 is formed under the reaction conditions, and deprotonation at the methylene unit near the CF3 group is highly favored because of the higher acidity, accounting for the observed high regioselectivity. In addition, the transient

• of 93%, the Pummerer rearrangement of sulfoxide 214 under harsh conditions turned out to be less efficient, affording 204f in only 42% yield. This reaction is thought to proceed stepwise via a first oxidative electron transfer, followed by deprotonation, a second oxidative electron transfer, and

• methoxylation or acetoxylation, respectively (Scheme 53). The driving force in this reaction is assumed to be the deprotonation of radical cation 215, a highly destabilized species due to the presence of the strongly electron-withdrawing CF3 substituent, which leads to radical 216, synergistically stabilized by

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• poly(allylamine) at pH 7.0. At this pH value, both the polyelectrolyte and also the photoacid are protonated [81][82]. Upon irradiation, the pKa of the photoacid decreases to pKa = −2.6 leading to deprotonation [82]. In addition to the electrostatic self-assembly of the photoacid and the

• time a peak emerges at λ = 300 nm. In addition, the band corresponding to the photoacid becomes less distinct. These two phenomena indicate the deprotonation of the photoacid and the transformation of Flavy from the A to the B form. After keeping the assemblies in the dark overnight the peak at λ = 550

• suggests that the changes of the structure depend on the deprotonation of the photoacid due to irradiation and the subsequently higher charged molecule. The last two steps for cycle II are as in cycle I and the size and structure of the assemblies switch back to the starting point. Interestingly, these two

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

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

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• did not occur at all when potassium carbonate was used as a base, because the deprotonation of phenol became slow due to the low basicity (Table 1, entry 9). With the optimal reaction conditions (Table 1, entry 8) in hand, we next examined the scope of the reaction (Table 2). When an electron-rich

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• (1). Alternatively, the (±)-euphococcinine precursor 6 was prepared from 4, via deprotonation, silylation, and finally, silyl ether cleavage. Swern oxidation of alcohols 5 and 6 gave aldehydes 7 and 8, treated with allylmagnesium bromide, to generate secondary alcohols 9 and 10. These alcohols were