Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives

• Valeriy O. Filimonov,
• Alexandra I. Topchiy,
• Vladimir G. Ilkin,
• Tetyana V. Beryozkina and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2023, 19, 1191–1197, doi:10.3762/bjoc.19.87

• elimination of hydrogen sulfide (Scheme 2). Thus, we have shown that when 2-cyanothioacetamides 1a–c react with hydrazine hydrate (3a) in ethanol, both groups (thioamide and cyano) interact with hydrazine with the elimination of hydrogen sulfide and the formation of 3,5-diaminopyrazoles 4a–c (Scheme 2). It

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• elimination) more commonly associated with transition metal-mediated chemistry; however, halogen- or σ-hole bonding has recently emerged as a credible explanation for the diverse reactivity that iodonium ylides undergo. σ-Hole bonding theory offers a means to explain the occurrence of transition metal-free

• literature to-date has shown that the vast majority of reactions follow the reductive elimination pathway to produce 4. However, a clear exception to this is in reactions with nucleophilic fluoride or [18F]fluoride, which reductively eliminate to exclusively generate fluoroarenes (e.g., 5). The rationale for

• reductive elimination of iodobenzene to give 11 (Figure 5, left). This was also the pathway subsequently suggested by Gallos et al. [116] for the synthesis of 13/14 from 12. In 2003, Hadjiarapoglou further investigated the intermolecular reaction between 8 and cyclopentene under thermal, metal-free

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• ) under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium (t-BuOK/DMSO). The fluorescent properties of the synthesized compounds were studied. 4-Arylpyrazolo[3,4-b]pyridin-6-ones luminesce in the region of 409–440 nm with a quantum yield of 0.09–0.23

• when irradiated with UV light. Keywords: 5-aminopyrazole; azlactone; elimination; fluorescence; one-pot synthesis; pyrazolo[3,4-b]pyridin-6-one; Introduction The pyrazolo[3,4-b]pyridine scaffold is present in many biologically active compounds [1][2][3][4][5][6][7][8][9][10][11][12]. Among them, 4

• (Table 1). For compound 3a, the possibility of benzamide elimination was studied. The benzamide fragment is a poor leaving group; however, in a superbasic medium, we were able to eliminate this group in compound 3a. In order to select optimal synthesis conditions, we heated compound 3a in DMSO at

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• with the elimination of a H+ ion to form the functionalized aromatic moieties. The aza-Friedel–Crafts reaction is a subclass of the originally reported transformation that couples an imine with an aromatic system allowing for a facile incorporation of an alkylamine functionality into the aromatic

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• removal of methanol, produces intermediate E. In the next steps, the ring closure of intermediate E due to the lone pair of nitrogen gives F, which after the elimination of methanol and water in subsequent steps provides intermediate H. Finally, an aromatic N-substituted pyrrole 3 is produced by basic

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• ), and, finally for 10, dehydration of the tertiary alcohol (mesylation and elimination) (Scheme 3), we decided to test their roles in the photoredox-catalyzed decarboxylative cyclization. With 8 and 10 in hand with the C4-prenyl side-chain already oxidized/functionalized, we recognized that this

• intramolecular 7-endo-trig ring closure) may well be the thermodynamic product based on the more stabilized benzylic radical that is produced [101]. As largely reported in the literature [102][103], radicals generated next to alcohols do not normally undergo β-elimination to give alkene/carbon–carbon double-bond

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the [Cun] catalyst and intermediate V. The critical β-H elimination step occurs smoothly in the presence of excessive base to generate the final nitrile product. Due to the high reactivity of the intermediate fluorosulfonate I, the attempt of isolation or detecting the in situ generated intermediate I

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• elimination of nitrous acid, accompanied by aromatization, yielded furan 13. In addition to the stepwise mechanism, a concerted ring-expansion can be also acceptable [25]. Conclusion Although nitrocyclopropanedicarboxylic acid esters 1a have been used in organic syntheses, nitrocyclopropanes possessing an

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• elimination delivers the desired product 44 via the intermediate 49 (Scheme 10b). It was proposed that the enantioselectivity was mainly due to the C–C reductive elimination of the R-pathway, which is lower in energy than the S-pathway. Remote C–H alkylation Several remarkable studies have been reported for

• addition of 1 gives the silyl-iridium complex 52. The insertion of aldehyde 50 into the Ir–Si bond of 52 provides the pyridyl alkyl iridium species 53 that finally by C–C formation via reductive elimination furnishes the desired products 51 along with the formation of an iridium hydride species (Scheme 11b

• of the alkene provides the intermediate 57 which on subsequent reductive elimination furnishes the C4-alkylated products 55. Based on the deuterium exchange experiment, the author suggested that the steps involved in the catalytic cycle from 56A to 57 are reversible in nature, which may activate the

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts. Keywords: Eschenmoser coupling reaction; Hantzsch thiazole

• with a α-haloketone or α-haloester II. The initially formed α-thioiminium salt III can undergo either a base-catalyzed elimination to give nitrile X and thiol IX [10][11][12] or cyclization to give a thiazole XIII or thiazolone XI depending on the substituent at the carbonyl group Y. Both side

• phosphite does not give 8a-Me at all. The combined yield of 8a and 8a-Me can be increased when trifluoroacetic acid is added (Table 1, entry 9). Its role probably involves an acid-catalyzed elimination of a water molecule from 7a or 7a-Me. On the other hand, the addition of a stronger base (triethylamine

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• for the formation of pyrimidines 9 is presented in Scheme 3. At first, intermediate A is formed by Michael addition of cyanamide to enaminone 13. Further elimination of dimethylamine leads to cyanoenaminone B. Next, interaction of the cyano group with dimethylamine results in the formation of

• -electrocyclization under UV irradiation resulting in the formation of unstable intermediate A, starting from which two directions of further transformation are possible. The most obvious pathway is a simple elimination of a methanol molecule with aromatization of the central benzene ring leading to polycyclic

• product 12. In addition to the considered variant thermal suprafacial [1,9]-H sigmatropic shift resulting in compound 11 is implemented in this case. This transformation is energetically favorable due to the restoration of aromaticity of the benzene and pyrimidine rings. At the same time, the elimination

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• yields with moderate to good diastereoselectivities via Michael addition and nucleophilic addition–elimination (Scheme 17) [39]. The synthesis is a [5 + 2] annulation fashion. The reactions of 2-phenyl/alkoxy-4H-benzo[d][1,3,2]dioxaphosphinin-4-ones 82 and dialkyl 2-benzylidenemalonates 78 produced

• '-carboxylates 83 in 5–10% yield as byproducts. The major products 84 were generated via Michael addition and the nucleophilic addition–elimination of the carbanion of the generated enolate moiety, while the oxyanion of the enolate moiety attacked the phosphorus to form the byproducts 83 (Scheme 18) [40][41

• –elimination. Both they are potential chiral phosphorus ligands (Scheme 20) [25]. When Fuchs and co-workers investigated the conversion of cyclic vinyl sulfones to vinylphosphonates, they found that the reaction of (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol (100) and diethyl phosphonate generated

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• , transformation to potassium trifluoroborate salt, hydrolysis, C–C cross-coupling, base-mediated elimination, radical C–B cleavage) [72]. Therefore, enantioenriched boronates are commonly applied intermediates in organometallic, medicinal, and other fields of chemistry. At the same time, some organoboronic acid

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• the case of a carbobicyclic system (Figure 2b), the rigidity of the bicyclic framework restricts β-H elimination. The inability to rotate to achieve an optimal synperiplanar geometry restricts efficient elimination (Figure 2b, Ha). Bridgehead protons are in a more favorable geometry for β-H

• elimination (Figure 2b, Hb); however, their elimination would generate a highly unstable alkene at the bridgehead, violating Bredt’s rule [9]. For these reasons, carbobicyclic alkenes have been exploited as propagation mediators, as seen in Catellani-type reactions [10][11][12]. In this review, we will focus

• exo coordination of a metal catalyst with the π system and migratory insertion, the resulting heterobicyclic alkyl metal intermediate is not as kinetically stable as its carbocyclic counterpart. While β-H elimination is still limited, these heterobicyclic alkenes will often undergo β-heteroatom

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• the presence of an electrophilic source or an oxidation/ligand exchange in the presence of a nucleophilic source (i.e., AgSCF3) and an oxidant (B in Scheme 4). Finally, after a reductive elimination step, the expected functionalized product 6 is obtained and the palladium catalyst is regenerated. In

• (KIE = 2.7). Subsequently palladacycle C is oxidized by Selectfluor® to form a palladium(IV) complex D. After a ligand exchange with AgSCF3, the intermediate E is obtained, which, after reductive elimination, releases the desired product 12 and regenerates the catalyst. Alternatively, a ligand exchange

• with AgSCF3 occurs before the oxidation step, generating the palladium(II) complex F. After an oxidative addition in the presence of Selectfluor®, the palladium(IV) intermediate E is generated. Finally, after reductive elimination step, the desired product 12 is released and the catalyst regenerated

Mechanochemical solid state synthesis of copper(I)/NHC complexes with K₃PO₄

• Ina Remy-Speckmann,
• Birte M. Zimmermann,
• Mahadeb Gorai,
• Martin Lerch and
• Johannes F. Teichert

Beilstein J. Org. Chem. 2023, 19, 440–447, doi:10.3762/bjoc.19.34

• indicated the presence of 5, but also of unwanted side-products that could not be identified. Purification of 5 from this complex mixture turned out not to be feasible. Further modifications of the milling conditions did not lead to the elimination of these side-products, therefore the experiments with NaH

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• ions. Further demethylation [40] and oxidation of the thioether followed by thermal elimination of the intermediate sulfoxide gave 2 in 98% yield after two steps (Scheme 7). The authors also achieved the synthesis of (±)-1 from combretastatin D-2 (2). Protection of the hydroxy group in compound 2 using

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• -hydroboration of the enone 29 with H-B-9-BBN to give an O-B-9-BBN enolate 30. Electrophilic cyanation of the enolate 30 with NCTS 31, and elimination gave the β-ketonitrile 33 and TsN(Ph)-9-B-BBN 34, which underwent B‒N/B‒H transborylation with HBpin to regenerate the catalyst and give TsN(Ph)-Bpin 35 (Scheme 8

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• the specific example given, elimination of the glucose 6-phosphatase activity would be sufficient to avoid this error. If this is not possible, the use of method 1 where one measures the approach to equilibrium from opposite directions of reaction could be advantageous. Specifically, one can plot the

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• reaction has never been used in the synthesis of natural products before this report, and no β-elimination of the silyloxy group was observed, although this often occurs in such systems [26]. The installation of the two alkenes in 37 required 13 additional steps, and further protecting group manipulations

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• intermediate A tetrahydrofuran intermediate B with cis-fused ring systems is formed as seen in the existing literature [7]. A proton transfer of enolate moiety B yields another enolate C followed by the β-alkoxy elimination [17] of intermediate C to form intermediate D. The intermediate D on protonation leads

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• from guaiol (61) by Wallach in 1894 [121] and again prepared by Gandurin in 1908 by elimination of the instable methyl xanthogenate (Scheme 16B) [122], followed by an isolation from Acorus calamus ([α]D20 = +13) by Šorm and co-workers [123]. It is well known that 56 can easily be dehydrogenated, e.g

• through 1,2-hydride shift to L3a and deprotonation (Scheme 16A). However, this compound itself is not known as a natural product, but has been obtained together with γ-gurjunene (64) from guai-11-en-5-ol (63), a natural product isolated from gurjun wood oil, by elimination (Scheme 16D) [131]. Conclusion

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• from a haliclona marine sponge [4], and vertinolide (5) from Verticillium intertextum [5] (Scheme 1). As outlined in Scheme 2, a variety of methods has been reported for the synthesis of conjugated dienones, mostly via addition/elimination reactions such as Knoevenagel condensation or Claisen–Schmidt

• deprotonated with LDA at −78 °C in THF and subsequently methylated to give 34 in 99%, followed by treatment with alkynyl Grignard reagent to give the tertiary alcohol 35 in 71% yield. Final elimination with MsCl and NEt3 yielded the desired enyne 25q (49%). When terpene enynes 25p and 25q were submitted to the

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reverse (3 + 2) cycloaddition which expels a heteroatomic anion via a β-elimination-type mechanism somewhat similar to a classical Grob-type fragmentation. Similarly, 1,3-dithiolanes undergo fragmentation at relatively low reaction temperatures, limiting their synthetic application to alkylation with

• highly reactive electrophiles. The homologous 1,4-dithianes or 1,4-dioxanes are readily available as simple building blocks, but also undergo a swift β-elimination following the metalation of one of their ring carbons, again limiting their appeal as building blocks [16][17]. In his landmark synthesis of

• generality in this aspect. In principle, 1,4-dithianes should offer good options for the development as C2-synthons that are complementary in scope to the more widely used 1,3-dithianes, but the β-fragmentation problem (cf. Scheme 2) hampers their easy derivatization. It should be noted that this elimination