gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• addition–elimination reaction, affording the corresponding fluorinated 13a–d (Scheme 4) and nonfluorinated 14a–d (Scheme 5) unsaturated products. Also this time, for compounds 13a–d, the formation of only Z isomers was observed (Scheme 4). The stereochemistry was determined by 19F{1H} NMR spectroscopy

• also tried to perform a substitution reaction by treating compounds 1a and 2a with tert-BuLi, employing methyl iodide as the electrophile. However, similar to previous reactions, this did not yield substitution products at the alpha position, but to the addition–elimination reaction products. More

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• 93 (Scheme 33) [116]. The presence of two equivalents of sodium hydride deprotonates the acidic α-NH of arylhydrazine, thereby determining the regioselective attack in addition–elimination sequence furnishing a hydrazine enaminone intermediate, and ultimately leading to pyrazole 93 after cyclization

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• the production of an alkyl radical. After that, this alkyl radical reacts with allyl and alkenyl sulfones in an addition–elimination cycle to produce the required product and a benzenesulfonyl radical. The benzenesulfonyl radical abstracts a hydrogen radical from the Hantzsch ester radical to form

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• latter undergoes addition–elimination reaction with another molecule of o-anisidine to give 2-(phenylamino)cyclohexa-2,5-diene-1,4-dione. The third unit of o-anisidine is added to the quinone via 1,4-addition, followed by oxidation of the 1,4-dihydroxy compound to give 2,5-bis((2-methoxyphenyl)amino

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

•  1). The H-bonding capable dihydropyrazinoquinoxaline diones (DPQDs) were obtained by a SNAr mechanism involving the corresponding DCPQ derivatives. Based on numerous examples in the literature, it has been established that for electron-deficient π-systems containing cyano groups, the addition

• –elimination pathway will dominate over hydrolysis. This preference was crucial to prevent the formation of undesired carboxylic acid products [28][30][31]. These results also align with the observations previously reported by Takeda and co-workers [24]. The reaction was carried out using a large excess (10

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• only 10 mol % of DIPEA (92% 19F NMR yield, Scheme 5b). This reaction could result from base-assisted nucleophilic attack of adventitious water present in the reaction mixture. In addition to addition/elimination of fluoride ions to thioesters 3, a second potential mechanistic pathway exists for the

• highly electrophilic compound can react with the carboxylic acid in the presence of DIPEA via addition/elimination affording a thioic anhydride species E and a fluoride ion [9]. Addition of F− to the carboxyl carbon followed by fluoride elimination from the resulting thiocarboxylate would provide acyl

• the acyl fluoride with addition/elimination of fluoride to a thioester intermediate and independent deoxyfluorination of a second equivalent of the acid substrate by the released −SCF3 anion both operating under the reaction conditions. This allows for the reduction in the loading of BT-SCF3 to sub

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• generate a large quantity of iodanyl radical from Ts-ABZ (3) homolysis and from the addition–elimination on Ph-EBX (2). Since no quencher is present in the mixture, we wondered if the accumulation of those radicals could be responsible for the low yields obtained. Addition of (TMS)3SiH, a H• donor

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• gem-difluoroalkenes with organic azides in morpholine as a solvent to construct fully decorated morpholine-substituted 1,2,3-triazoles. Mechanistic studies revealed the formation of an addition–elimination intermediate of morpholine and gem-difluoroalkenes prior to the triazolization reaction via two

• cycloaddition or addition–elimination reactions with 1,3-dipoles and gem-difluoroalkenes is largely unexplored and the only report of a cycloaddition is with 2-fluoroindolizines (Figure 1A) via a β-fluoride elimination in an SNV (nucleophilic vinylic substitution)-like transformation [9]. Nucleophilic addition

• ). We observed addition–elimination intermediate of morpholine and gem-difluoroalkenes INT-1, (−99.9 ppm, d, J = 35.7 Hz) within 30 min of the reaction and a gradual consumption of the gem-difluoroalkene 1 (−83.67 ppm, dd, J = 33.8, 26.4 Hz and −85.78, dd, J = 33.8, 3.8 Hz) throughout the course of 8 h

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

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

• -[1,1'-binaphthalen]-2-ol (97) with n-BuLi and TMEDA followed by addition of phenylphosphonic dichloride generated a pair of diastereomeric (M,4R)-4-phenyl-5H-dinaphtho[2,1-d:1',2'-f][1,2]oxaphosphepine 4-oxides 98 and 99 in low yields and low diastereoselectivity via double nucleophilic addition

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

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

• vicinal position of 2H-imidazole and the addition–elimination pathway providing the products 10a–h or addition–oxidation pathway affording the corresponding products 11a–h (Scheme 2). At first, pentafluorophenyllithium (13) which was produced through the reaction between n-BuLi and pentafluorobenzene (12

• ), acted as the nucleophile to attack the C-5 position of 2H-imidazole 1-oxides 9a–h to form the σH-adduct 14. The use of a deoxygenation agent in the mixture led to the formation of the desired products 10a–h via “addition–elimination” (SNH AE, path A) from the adduct 14 with the elimination of the good

• perfluoroaryl-substituted 2H-imidazole products, a push–pull fluorophore system was discovered, which can be useful for the preparation of fluorometric sensor materials because of the solvent-dependent intramolecular charge transfer effect (ICT). Here, two reaction pathways were designed: (A) addition

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• for the reaction between N6-substituted adenine anions 1–5 and FcCOCl. In no case the tetrahedral intermediate, typical of a nucleophilic addition–elimination pathway, was located as a genuine minimum on the potential energy landscape. Instead, the structure with tetrahedral geometry corresponds to

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• S-methyldibenzothiophenium ion [39] when used as the standard SN2 substrate for solvolyses over a wide range of solvents and the range of l values suggests that the addition–elimination pathway appears to be disfavored for sulfonyl chlorides. The m values (Table 2) are consistent with the solvation

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

• mechanisms for this formation. The first one consists of a direct intramolecular addition–elimination of the triguanide into triazine (path A); and the second involves a tautomeric exchange and subsequent amine elimination from the cyclic aminal intermediate (path B). The isolation of the trisubstituted

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

• triazole 1b' did not afford the expected product 3f (Scheme 3d). This suggests that triazole 1b' is not the active nucleophile in this transformation. However, when the O-tosyl intermediate 4b was treated with a more nucleophilic amine, namely benzyl amine 5a, it indeed afforded the Michael addition

• –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

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• with a tributylstannyl group to give 133 was accomplished by the reaction with (Bu3Sn)2CuLi in THF at −78 °C. The reaction took place following an addition–elimination mechanism. Then, coupling of 133 with iodobenzene in the presence of Pd(PPh3)4 and CuI as the co-catalyst afforded ethyl (E)-3-phenyl-3

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• a yield of 86%, the pyrazolo derivative 10p could only be obtained in a moderate yield of 38%. This might be explained by the tendency of the pyrazolo moiety to act as a leaving group and a following addition–elimination reaction with methanol can take place (the corresponding 2-methoxy-substituted

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

• Itamar L. Gonçalves,
• Rafaela R. da Rosa,
• Vera L. Eifler-Lima and
• Aloir A. Merlo

Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20

• in the reaction of thiourea with primary amines [6]. Another important synthetic route for substituted thioureas is a two-step approach: (i) the addition/elimination reaction of benzoyl chloride, with a thiocyanate salt, generating in situ, benzoyl isothiocyanate, and (ii) an appropriate amine

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• /Cvinyl–CF2H bonds followed a radical addition–elimination process (Scheme 73). Subsequently, Bouyssi and co-workers [135][136][137] used Togni’s reagent to conduct the trifluoromethylation of (hetero)aromatic aldehydes or corresponding N,N-dialkylhydrazones with CuCl as the catalyst at room temperature

An efficient and concise access to 2-amino-4H-benzothiopyran-4-one derivatives

• Peng Li,
• Yongqi Wu,
• Tingting Zhang,
• Chen Ma,
• Ziyun Lin,
• Gang Li and
• Haihong Huang

Beilstein J. Org. Chem. 2019, 15, 703–709, doi:10.3762/bjoc.15.65

• Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, P. R. China 10.3762/bjoc.15.65 Abstract A highly efficient and convenient protocol was developed to access 2-amino-4H-benzothiopyran-4-ones through a process of conjugated addition–elimination. The sulfinyl group was proved to

• good yields and excellent chemical purity without requiring column chromatographical purification. Keywords: 2-amino-4H-benzothiopyran-4-ones; addition–elimination; scale-up synthesis; sulfinyl group; Introduction Benzothiopyranones are a class of molecules displaying biological activities in part

• group to afford the desired 2-amino-4H-benzothiopyran-4-ones through conjugated addition–elimination by nucleophiles. Subsequently, substrates 2a and 3a were reacted with a variety of alkyl/arylamines in the optimized solvent isopropanol (Table 2). Substrate 2a having an ethylsulfinyl group in general

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• considered as nucleophilic substitution of hydrogen (SNH) in non-aromatic N-oxides of 2H-imidazoles 1a–d. It has also been shown that the SNH reactions can be realized via either an "addition–elimination" SNH(AE) mechanism, or through an "addition–oxidation" SNH(AO) scheme to form imidazolyl carbonanes 4a–d

• carboranyllithium, generated in situ from commercially available o-carborane. It has also been found that the SNH(AE, «addition–elimination») scheme leads to carboranyl-substituted 2H-imidazoles, while alternative SNH(AO, «addition–oxidation») results in the corresponding N-oxide analogues. In summary, novel

• -oxides 1a–d and carboranyl lithium 2. The reactions were carried out in accordance with the optimized coupling conditions according to the "addition–elimination" SNH(AE) or "addition–oxidation" SNH(AO) pathways (Table 1 and Table 2). Optimization of the reaction conditions for the C–H/C–Li cross-coupling

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• literature data and our experimental observations. N-Aryl-3,4-dihydroquinazolines 1. Reaction intermediate in the synthesis of compound 2a. Synthetic pathway leading to N-aryl-3,4-dihydroquinazolines 1. Synthesis of compounds 2. Addition–elimination mechanism for the heterocyclization. Proposed mechanism

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• extension occurs as expected, most probably via addition/elimination, including a pentavalent intermediate and possibly by a pseudorotation to place the ethylimidazole leaving group in an apical position. Since either of the two alcohols of the terminal diol of the primer can attack, a mixture of 3',5'- and