Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• pyridine rings, the naphthalene core at positions 5(8) and the CH2CH2 bridge (dehydrogenation) undergo chemical modifications under mild conditions, giving the corresponding acenaphthylenes. The latter can also be obtained in an unusual way by tele-elimination from 5,8-dibromodipyridoacenaphthene by

• effect of functional groups on the further chemistry and basicity of the newly synthesized derivatives is also considered. Results and Discussion Amination, dehydrogenation, and supramolecular aggregation Direct amination of quinoquinoline 5 could potentially lead to 2(11)-substituted amines 6 (Figure 1

• activity/inactivity in amination reactions. It is known that acenaphthylenes are usually readily formed from acenaphthenes by dehydrogenation with chloranil, dichlorodicyanobenzoquinone (DDQ) or active MnO2 on reflux in toluene/xylene and other inert solvents. However, attempts to obtain acenaphthylene 8

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• reaction, followed by a Au(I)-catalyzed [4 + 2] cycloaddition reaction to afford the target substrate 96 and its regioisomer 95 in a 2:1 ratio (Scheme 20). POA 87 was obtained on Au(111) at 610 K after Ullmann-type coupling and aromatic dehydrogenation of compound 96. Apart from these studies, the

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• interest in developing novel methodologies in this field of organic chemistry. Keywords: alkylation; cross-dehydrogenation coupling; ether; non-noble metals; Introduction Since the 1970s, organic chemists have developed many selective cross-coupling methods for the construction of C–C bonds, such as the

• , tetrahydrofuran or tetrahydropyran can smoothly react with many methyl aryl ketones to obtain the desired coupling products (Scheme 6a) [54]. The mechanism of the dehydrogenation cross-coupling reaction may undergo a radical pathway. Initially, the tert-butoxy radical produced by the dissociation of t-BuOOH may

• synthesis of compounds with quaternary centers and natural products with high structural complexity. In 2014, Li et al. reported a CuCl2-catalyzed cross-dehydrogenation coupling reaction of C(sp3)–H bonds adjacent to an ether oxygen and the C(sp3)–H bonds at the α-position of a carbonyl functionality in the

Enabling artificial photosynthesis systems with molecular recycling: A review of photo- and electrochemical methods for regenerating organic sacrificial electron donors

• Grace A. Lowe

Beilstein J. Org. Chem. 2023, 19, 1198–1215, doi:10.3762/bjoc.19.88

• electrochemical hydrogenation methods might be more appropriate [41][42]. There is already work on electrochemical dehydrogenation of LOHCs [76][77]. In one example, DDQ was used to remove hydrogen from secondary amines by oxidizing them, followed by reoxidation of the hydrogenated DDQ at the electrode to

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• of o-nitrotoluene (22) Reduction to 2,2'-diaminobibenzyl (20) Ring-closing via amine condensation Catalytic dehydrogenation 1.1 Oxidative coupling of o-nitrotoluene (22) and reduction to 2,2'-diaminobibenzyl (20) The preparation of dinitrobibenzyl (21) can be achieved by the oxidative coupling of

• [36] via the polyphosphoric acid (PPA) catalysed cyclisation of 2,2'-diaminobibenzyl (20) at elevated temperatures (Scheme 3) [37][38]. 1.3 Catalytic dehydrogenation An early synthesis of 5H-dibenzo[b,f]azepine (1a) involved the gas phase dehydrogenation of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) to

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

• oxanorbornenes; however, the latter two substrates did not undergo dehydrogenation, generating cis-selective annulated coumarins (10b and 10d). In 2006, the same group applied this methodology for the total synthesis of arnottin I (10h), a coumarin-type natural product isolated from the bark of the Xanthoxylum

• 10. The selectivity for the non-dehydrogenated coumarins 10d is not understood, but 10b likely does not undergo dehydrogenation because there is no formation of aromaticity to drive the reaction forward. When the bicyclic alkene is substituted unsymmetrically at the bridgehead position, the reaction

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

• ., by heating with sulphur, to the blue azulene derivative 62 (Scheme 16C) [121][122][124][125][126], but the structure elucidation of this compound was only completed in 1936 [127]. Based on a comparison of IR spectra of natural terpenes, their hydrogenation and dehydrogenation products, the correct

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

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

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

• alternative approaches exist. The direct dehydrogenation of 1,4-dithiane is somewhat cumbersome [25], and, moreover, 1,4-dithiane (1) is surprisingly not available in large quantities at a reasonable cost, in spite of its apparent simplicity. Our lab has found that the synthetic method for dihydrodithiins

• then brominated with an excess of bromination reagent, which effects the 1,2-sulfur-migratory ring expansion, followed by bromination-induced dehydrogenation to the aromatic ring [31]. At the time of writing this review, the resulting benzoannelated dithiane 5 is also commercially available in small

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• opening of the epoxide (15%). From 41 having the correct tetracyclic skeleton, a transient protection followed by Petasis olefination, deprotection, selenide-mediated α,β-dehydrogenation and Mukaiyama oxidation afforded an advanced intermediate 42 bearing most of the target’s functionalities. A sequence

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• activation for hydrogenation of various organic substrates. More recently, SET reactivity of FLP was discovered [155]. The FLP-catalyzed dehydrogenation of N-protected indolines with H2 release [156] is depicted in Scheme 39. According to the proposed mechanism, the reaction starts with a hydride transfer

• heterocyclizations. Electrochemical N-ammonium ylide-catalyzed CH-oxidation. Oxidative dimerization of aryl- and alkenylmagnesium compounds catalyzed by quinonediimines. FLP-catalyzed dehydrogenation of N-substituted indolines. Funding This work was supported by the Russian Science Foundation (Grant no. 21-13-00205).

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• ][42], we found that cyclometalated iridium catalysts can effectively catalyze the dehydrogenation of alcohols to produce carbonyl compounds and hydrogen gas. Therefore, we used cyclometalated iridium complex (TC-6) to catalyze the ADC reaction of o-aminobenzyl alcohols 1 and aryl/heteroaryl/alkyl

• released from the dehydrogenation of 2-aminobenzyl alcohol/1-phenylethanol according to the previous literature [28]. Lastly, the desired product 3aa was obtained by the condensation and cyclization of the aldehyde 5 with acetophenone (6) under base conditions. The potential antimicrobial activity of the

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• (12) scaffold to 7β-hydroxythalianol, while CYP705A5 is a desaturase and introduces a double bond at C15 [41]. The related Arabidopsis CYP705A1 (also from clan 71) accepts a slightly different scaffold, arabidiol (11), triggering cleavage of the side chain at the same C15 instead of dehydrogenation

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• applications. NiO2, on the other hand, was used to achieve the dehydrogenation of amines (to nitriles) and to perform the α,β dehydrogenation of ketones 61. 3.2.3 Using chemically active fixed beds (catalysts): Copper metal in the form of wires or turnings can also be inductively heated when placed inside flow

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• moiety in 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), it was well established as a hydride transfer reagent in various organic reactions [14][15]. Generally, DDQ assists in dehydrogenation reactions in organic synthesis [16]. In this context, various carbon–heteroatom bond formation reactions such

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• 1,3-butadiene, followed by dehydrogenation gave menadione (10). This proved to be a good synthetic route, leading to menadione in approximately 80% overall yield (Scheme 6). Another interesting synthetic approach was reported by Mal and co-workers, who synthetized menadione (10) via a

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• afforded the products in excellent yields. The authors also conducted various experimental and theoretical studies to analyze the reaction mechanism. The proposed mechanism begins with the oxidative dehydrogenation of the alcohol to afford the aldehyde which undergoes condensation with ammonia to give the

• corresponding imine. Finally, oxidative dehydrogenation results in the formation of the nitrile. Conclusion This review summarizes the recent progress in ruthenium-catalyzed cyanation reactions. Due to the wide application of nitrile compounds in pharmaceutical and biological fields, cyanation reactions have

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• that, the cyclocondensation [29] of the halogenated anthranilamides 6a,b with benzaldehyde followed by dehydrogenation promoted by iodine gave the corresponding quinazolin-4(3H)-ones 7a,b, which we used in the next step without purification. Finally, chlorination [31] of quinazolin-4(3H)-ones 7a,b by

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• accelerating imine formation (I-19), and under the catalysis of a chiral phosphoric acid, intramolecular nucleophilic addition occurs to form I-20, followed by oxidative dehydrogenation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). In the presence of 10 mol % chiral phosphoric acid CPA 7, the axially

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• through reversible reaction with this cationic species. Conclusion In summary, we have achieved the electrochemical dehydrogenation cross-coupling of tetrahydroisoquinolines with terminal alkynes in continuous flow through Cu/TEMPO relay catalysis. This work demonstrates that continuous-flow

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• selective acetylation [43], followed by oxidation. Enones 4 and 8 were prepared by dehydrogenation of corresponding ketones with SeO2 in refluxing acetic acid [44]. Microwave-assisted heating of the reaction mixture in a closed vessel (150 °C) helped in decreasing the reaction time for dehydrogenation

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• benzylideneacetone in acetonitrile in the presence of p-TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels–Alder

• dehydrogenation reaction was carried out in acetonitrile at room temperature. A series of aromatized pyrrolo[3,4-c]carbazoles 4a–l were successfully synthesized by the one-pot two-step reaction and the results are summarized in Table 1. All reactions proceeded smoothly to give the corresponding pyrrolo[3,4-c

• active diene, indole-substituted chalcones. Then, the p-TsOH-catalyzed Diels–Alder reaction of indole-chalcones with second chalcones and sequential aromatization through DDQ dehydrogenation resulted in the polyfunctionalized carbazoles 6a–l in good yields (Table 2). Additionally, the similar reaction

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

• highly oxidizing conditions, dehydrogenation of the resulting cyclohexadienol would give 11.The electron-rich 4-hydroxy[2.2]metaparacyclophane (9) participates in ortho selective nitration to give 5. Nitric acid has previously been used to oxidize phenols to cyclohexadienones [69][70], and a plausible

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