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

• –H activation involving carbon–metal bond or a mechanism involving the usual metal-mediated coupling pathways comprising oxidative addition, transmetalation and reductive elimination steps, they are beyond the scope of this review and will not be extensively covered herein. Homogeneous and

• /hemiacetal avoiding undesirable elimination to the enamine, or attack at other electrophilic sites in complex substrates. The presence of a fluorine source like diethylaminosulfur trifluoride (DAST) or the Lewis acid boron trifluoride diethyl etherate (BF3·OEt2) result in the formation of reactive iminium or

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

• no α-proton to the N-F site proved to be a good choice for fluorinating enolate anions (Scheme 24). The side reaction, involving HF elimination, and which was a problem in reactions with the Barnette’s reagents 4-1 having the α-proton(s) except for 4-1b [26], was avoided here. The HF elimination is a

• β-elimination of HF proved to be an obstacle for the fluorination of strong bases such as phenyllithium. 1-13. N-Fluoro-o-benzenedisulfonimide In 1991, Davis and co-worker reported N-fluoro-o-benzenedisulfonimide (NFOBS, 13-2) as a fluorination reagent. NFOBS was prepared by the direct fluorination

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

• elimination to produce 23C, whereby the addition of BPh3 presumably accelerates this process [65]. Subsequently, the manganese species participate in the catalytic cycle by yielding alkynylated product 25. However, the mechanism entailing oxidative addition, followed by reductive elimination could not be

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

• key considerations were elimination of electrostatic repulsion (neutral backbone) and synthetic accessibility (simple to make achiral amide linkages) [3]. The design was guided by a simple computer model where the natural sugar-phosphodiester backbone of the Hoogsteen strand of a T•A–T DNA triplex was

• min in mice) through the kidneys after administration to animals by either intravenous or intraperitoneal injection [16]. In another study, PNA elimination half-life in rats was ≈17 minutes and ≈90% of PNA was recovered unchanged in the urine 24 h after administration [17]. To address these problems

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

• subsequent elimination of HBr leads to the triazole ring [39]. Another metal-free strategy to 1,4,5-trisubstituted 1,2,3-triazoles 8 was realized by regioselective reaction of aryl azides 7 with enaminones 6 in the presence of triethylamine, water, and ionic liquid (IL). This method exhibits good functional

• investigated by means of DFT calculations using the reaction between enaminone 6a and phenyl azide. TS1 and TS2 have been proposed as two transition states, which then converted to IN1 and IN2 as two possible isomers. The stable final products were achieved via a cascade reaction including the elimination of

• is imine–enamine-tautomerized to afford the intermediate 27. Then, the final triazole compound, as major isomer, is achieved through an intermolecular cyclization process and elimination of one unit of TsNH2 [23]. A general strategy was described for the synthesis of 1,4,5-trisubstituted glycosyl

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

• carboxylate-assisted C−H cleavage to deliver copper(II) intermediate A. Next, the copper(III) carboxylate species B is generated. Thereafter, a facile base-assisted ligand exchange is followed by reductive elimination to afford the alkynylated benzamide D. Finally, the desired isoindolone 3 is formed via an

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

• than Pd(II)-catalytic types have also been explored. Pd(II)-catalyzed hydroalkylation reactions The σ-alkylpalladium species formed after a carbon nucleophilic attack on an alkene double bond (Scheme 1) have a marked tendency to undergo a hydride β-elimination process that leads to oxidative coupling

• -substituted β-diketones 2a and 2b (61 and 70% yield, respectively). Notably, the unsaturated carbocycles expected from palladium β-hydride elimination were not observed, indicating that an oxidant was not required in the reaction medium to regenerate the Pd(II) species. Later, deuterium-labeling experiments

• counterparts, and so therefore are examples of quaternary centers generated by this means. The tendency of σ-alkylpalladium complexes to undergo a β-hydride elimination process is the major obstacle associated with the development of successful methodologies to promote intermolecular hydroalkylation of

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• hole-type conductivity with μh = 1.2⋅10−3 cm2⋅V−1⋅s−1. Therein, the thermolysis of a thin film of the device at 220 °C, accompanied by the elimination of Boc groups, led to a significant decrease of the OFET performance. For the example of the polymers 52 series, the importance of the spatial

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• ) [13], from which we recently effected coupling to yield a protected C6 hydroxamate [11]. Accordingly, 1 was stirred with PyBOP and DIPEA in CH2Cl2 for 5 minutes, before 3-aminopropionitrile was added. After stirring for 1.5 hours at room temperature an undesired C4–C5 elimination material 3 was

• isolated as the major product in 35% yield, with only a trace amount of the desired 2 formed (7% yield). The ability of 3-aminopropionitrile to act as a base and trigger this elimination was comparable to results we observed using N,O-dibenzylhydroxylamine as the coupling partner [11]. In the latter

• instance we were able to modify the nucleophile component to O-benzylhydroxylamine and supress unwanted elimination. Unable to do this here, we instead reduced the reaction temperature to 0 °C, maintaining this for 40 minutes. Pleasingly, the yield and product distribution were improved, affording

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

• source. Compound 14 could only be purified by recrystallization; all attempts to purify 14 by column chromatography led to complex mixtures of which the only identifiable product was 15. Even recrystallization can be problematic. Heating 14 leads to an elimination reaction that re-forms the initial

• compound 6. It is unclear how the denitration product 15 forms. Elimination of the ether 14 to regenerate the enone 6 is straightforward, but reductive denitration is a taxing reaction that normally requires strongly reducing conditions or a single electron donor. There are examples of milder denitrations

• than three repeats quoted). Possible mechanism for the formation of [2.2]metaparacyclophane 5 and cyclohexadienone cyclophane 6 from [2.2]paracyclophane 1. Conjugate addition of methanol and subsequent elimination. Supporting Information Supporting Information File 208: Metaparacyclophane spectra

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• + 2]-cycloadduct 10b undergoes spontaneous elimination of MeOH, yielding the aromatized product 9d. A similar mechanistic scenario was observed and discussed previously for the reactions of trifluoroacetonitrile imines 7 with enol ethers used as dipolarophiles [27]. An additional experiment deserves a

• case, the subsequent elimination step leading to an aromatized product cannot take place. All products of the type 9 are colored, typically pale yellow, both in the solid state and in solution. The UV–vis spectroscopic analysis of the naphthoquinone-derived series (compounds 9a–h) revealed less intense

• elimination of MeOH from the initial [3 + 2]-cycloadduct of 1d and nitrile imine 7d generated from 8d. Formation of the thermally stable, initially formed [3 + 2]-cycloadduct 10c obtained from 1e and nitrile imine 7d generated from 8d. Results of the [3 + 2]-cycloaddition of quinone 1a with the fluorinated

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• 3a as an example, as depicted in Figure 5. We suggest that the reaction is initiated by iodine-mediated activation of the secondary alcohol in compound 1a (A), followed by elimination of HOI to generate the vinyliminium ion species B (see mesomeric structure C) [52]. This electrophilic intermediate

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

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• hydroperoxy radical that can next evolve into an aldehyde by β-elimination of water, or after reduction, into an alcohol. The stability of the radical 10 is surprising. Stable radicals (O2, NO, nitroxyl derivatives, DPPH) are characterized by a two-center three-electron bond [56]. Conversely, the stability of

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

• silica are suggested to play a key role in the water elimination step. Furthermore, the primary amine function on the silica shows better outcomes compared to a tertiary amine. Different products were prepared in moderate to excellent yields, however, with the less acidic diethyl malonate the catalyst

• %) over 10 hours of continuous runtime [155]. As such a simple chromatographic column can be exploited as flow reactor to perform initial feasibility tests. As with all condensation reactions, the main problem when performed in flow is the elimination of water. Yeung et al. provided a solution using a

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

• using DMF as solvent. After addition, a subsequent intramolecular cyclization involving the resulting amide and the vicinal carbon with bromine atoms took place. By contrary, when the reaction was carried out in THF, the elimination process was suppressed, leading exclusively to enantiomerically pure α

• dienolate reacted at α-position with the chiral imine 14. The addition was highly diastereoselective, being the configuration of the newly created stereogenic center dependent on the configuration of the sulfur atom of the starting imine 14. After nucleophilic addition, and subsequent elimination, 3

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• . These observations are consistent with the recently reported instability of O-acylated GlcNAc under basic conditions due to elimination reactions of transient hemiacetal intermediates [38]. This instability of amino sugar hemiacetals underscores the requirement to both protect the anomeric position with

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• -hydroxyaryl)enones underwent cyclization to ketals (chromanols) after the addition of boronic acid. The prepared chromanols afforded the chromenes through elimination upon treatment with p-TsOH. A series of different β-(2-hydroxyaryl)enones and boronic acids was tested and provided the substituted chromenes

• in the presence of water, it is selectively converted to the 1,4-addition product instead of undergoing a β-hydride elimination leading to an oxidative Heck product [3][26][35]. In 2005, one month after the very first report of the addition of aryltrifluoroborates to enones by Miyaura [32], the

• -hydride elimination. However, the obtained yields were inconsistent. The usage of Pd(TFA)2 led to a better reproducibility of the results. From the various diphosphine ligands tested, (R,R)-MeDuPhos (L2) was identified as the one leading to the best level of enantioselectivity (up to 99% yield and up to

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• derived from oil but from biorenewable resources, is a topic of primary importance in modern chemistry [1][2]. The solvents are the major contributor to the waste generated in chemical industries, and the elimination or replacement of these with more sustainable alternatives is part of the efforts of the

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• in low to moderate yields (8–40%). The authors moreover proved that the reaction occurs at the stage of the symmetric biguanide intermediate via the elimination of 2-naphthylamine. Moreover, it was shown that the stereochemical outcome of the addition step was dependent on the substrate. Usually, the

• ]. The reaction proceeded via cyclization of the oxime intermediate in ethanol at room temperature in 45% yield. Otherwise, Kumar et al. reported the formation of the hydrolysis product 1,2,4-oxadiazol-5(4H)-one (Scheme 29B) after acidification and elimination of ammonia [64]. Overall, despite quite

• can act as a “bisamidine transfer agent” by the addition of an amine, and subsequent elimination of the leaving group. Two types of “biguanide transfer agents” have been developed so far. Depending on the nature of the leaving group they can be separated into either pyrazole or thiomethyl agents

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

•  18). A sequence of reactions involving elimination of a proton from 83, treatment of 84 with an alkoxide, and protonation of the resulting enolate delivered thermodynamically favored equatorial ester 80 and 81. The highly diastereoselective Brønsted superacid-catalyzed Prins cyclization of

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• (sp3)–H bromination reaction. The proposed reaction mechanism is shown in Scheme 5, which involves the following steps. (1) The reaction between NBS and TMSN3 generates bromine azide via the elimination of N-(trimethylsilyl)succinimide [52][53]; (2) bromine and azide radicals are then formed via

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• consecutive ring closure yields the desired product 75 aided by the attack of nitrogen lone pair in Michael’s adduct C via a sequential ethanol elimination (E) from D followed by aerial oxidation of intermediate F. Another proposed mechanism follows the formation of imine derivative G produced by the reaction

• condensation between ketone and formylquinoline. The amine and the intermediate A undergo Michael addition furnishing the keto-amine B. Further, an intramolecular cyclization with the attack of the amino group onto the carbonyl functionality with subsequent elimination of a water molecule results in the

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• –elimination product 6b in good yield. These results provided crucial evidence for the mechanism of the reaction which suggested that β-sulfonyloxyenone could be the key intermediate in the formation of β-triazolylenone 3. Based on the above control experiments, the following mechanism is proposed. Initially

• anion III on the enone intermediate 4 (path A), followed by elimination of OTs affords the corresponding β-triazolylenone 3 (Scheme 4) [52]. The β-O-tosylcyclopentenone intermediate 4b can also undergo intramolecular tosyl migration to form a stable C-tosylated product 4b’ (see also Scheme 3b and c

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• thermal addition of diazo compounds (the well-known carbene precursors), followed by N2 elimination. However, it occurs much more difficultly for diazo compounds than with singlet carbenes. This is due to the formation of a mixture of [5,6]-closed and [6,6]-open isomeric cyclic adducts. This phenomenon

• C60 or b) possible formation of both isomers as a result of 1,3-dipolar cycloaddition of the diazo compound to the fullerene, followed by elimination of molecular nitrogen from the pyrazoline intermediate. Second, the rearrangement of [5,6]-open isomers into thermodynamically more stable [6,6]-closed