Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• ][41][42][43][44]. The group of Wang recently reported the sacrificial anode-free electroreduction of benzophenone derivatives to afford vic-1,2-diols using over-stoichiometric NaN3 under acidic conditions, but appropriate precautions should be taken for in situ-generated explosive and toxic HN3 [45

• -2a was subjected to the present reaction conditions, oxidative C–C bond cleavage of dl-2a proceeded to give the corresponding ketone 3a (Scheme 5b) [48]. Recovered 2a was found to be a mixture of dl and meso isomers, indicating that homocoupling of in situ-generated ketone 3a occurred under the

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• , phenacylmalononitrile is also a readily available substrate, which can be easily prepared through a base-promoted substitution reaction of phenacyl bromide with malononitrile under mild conditions [11][12][13][14][15][16]. In many practical cases, phenacylmalononitriles could be conveniently generated in situ by

• final product 4. It is due to the in situ formation and ring-opening of 2-oxabicyclo[2.2.1]hept-5-ene, that only one diastereoisomer 4 with the aryl group and the remaining cyano group in cis-position was selectively formed in the domino reaction process. In order to shed light on the proposed reaction

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• NHCs are generated in situ, where they may be used as basic or nucleophilic species. Due to the difficulty isolating highly reactive NHCs, the concentration of the obtained NHC solution can be determined indirectly by addition of elemental sulfur after the electrolysis, which realizes quantitative

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• [34], dibromodithienothiophene 24 is lithiated with n-butyllithium at −90 °C, and the resulting species is reacted in situ with triisopropyl borate. After aqueous workup, dithieno[3,2-b:2’,3’-d]thiophene-2,6-diylboronic acid (25) is obtained, enabling subsequent Suzuki–Miyaura cross-coupling [36

• derivative of 31 could be isolated; it hydrolysed on the column back to the starting material. Thus, after reacting 31 with n-butyllithium and trimethyl borate, the obtained species was reacted in situ with pinacol to generate the corresponding boronic ester 32, which could be isolated by column

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• phenylacetylene (3a) was used as a model reaction to determine a suitable base and an equivalent number of reagents (Table 1). The key intermediate 2a was prepared in situ from 1a (0.5 mmol) and Se powder (0.5 mmol) in the presence of 10 mol % of CuI and 1,10-phenanthroline at 130 °C in DMSO under aerobic

• , under an argon atmosphere, the reaction yield decreased by approximately half. This reaction, without Na2CO3 as base, also afforded 4aa in 85% yield (Scheme 1, reaction 1). Although bis(imidazo[1,2-a]pyridin-3-yl)monoselenides 5 could form in situ [32], the reaction of 5 with acetylene 3a under the

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• isolated in 78% yield after chromatography. The use of stoichiometric amounts of both partners led to incomplete conversion, with about 1/3 of the starting hydrazine being recovered after two days of reaction. We then tested 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ), in dioxane, a method for in

• situ generation of a mixed anhydride [45]. This method gave the highest coupling yield to dimer 2d, but again with the condition of using an excess of the acid partner, as some of it was consumed to give the byproduct ethyl ester 1e. Dimer 2d was obtained for example in 95% yield from 1.5 equivalents

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• ][48][49][50]. On the other hand, the Diels–Alder reaction of the in situ generated indole-2,3-quinodimethanes with various dienophiles is also a powerful method for rapid construction of functionalized tetrahydrocarbazoles [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. In

• -acetate for the efficient synthesis of diverse spiro tetrahydrocarbazoles. In the presence of CuSO4, the multicomponent reactions of aromatic aldehydes, 2-methylindole and various cyclic dieneophiles such as 3-phenacylideneoxindoles, isatylidene malononitriles and the in situ generated 5-arylidene-1,3

• dienophiles, 5-arylidene-1,3-dimethylbarbituric acids, could be in situ generated by aromatic aldehydes and 1,3-dimethylbarbituric acid under the standard conditions. Therefore, the four-component reaction was carried out by using two molecular aromatic aldehydes, 1,3- dimethylbarbituric acid and 2

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• generated in situ from propiophenone, and second, the deprotection of propiophenone α-thioesters in the presence of perfluoroalkyliodides and subsequent oxidation of the formed perfluorothioether into the sulfone. However, none of these proposed pathways gave yields high enough for the reaction to be

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• azomethine ylides generated from primary or secondary α-amino acids and carbonyl compounds such as alloxan, isatin, tryptanthrin, and 11H-indeno[1,2-b]quinoxalin-11-one were performed in a multicomponent fashion [19][20][21][24]. In these reactions, the azomethine ylides generated in situ are highly reactive

• excellent chemical trap for detecting parent cyclopropene. Having carried out the experiment with ylide 1 as a trap in a similar fashion, we found that PRP (1) is unreactive towards parent cyclopropene (2p) under these conditions. Cyclopropene 2p, generated in situ from allyl chloride [41] and driven into a

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• was replaced by the Zn/Cu couple which was prepared without any metal activation by in situ ball milling of zinc and copper dusts. The advantage of the ball milling process is that the whole procedure is operationally very simplified. The reactive alkene generated was trapped in situ by several dienes

• polycyclic molecules given in Figure 1 are interesting reactive intermediates which could be applied in the Diels−Alder reactions of less reactive or thermally susceptible dienes. Often, these are generated in situ and trapped with dienes in a single pot, such as 7-oxanorbornadiene imides 1–3. For instance

• ] could be simplified by in situ generation of the catalyst. Moreover, in the debromination of norbornene imide 11, the expected Diels−Alder adduct with furan was not obtained, but compound 12 incorporating a tetrahydrofuran ring at position 2, presumably by radical reaction (Figure 2) [19][20]. We

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

• coupled with in situ generation of the azide from the corresponding bromide. The 1,2,3-triazoles are formed in up to 99% yield and in less than 10 minutes residence time, which includes azide formation prior to the cycloaddition step. Interestingly, this process could not be successfully repeated under

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• reaction dynamics and characterization of the products was achieved by in situ Raman and ex situ NMR spectroscopy and PXRD analysis. A strong influence of the different 4,4’-substituents of azobenzene on the halogenation time and mechanism was found. Keywords: azo compounds; halogenation; mechanochemistry

• -bromosuccinimide (NBS) under neat grinding (NG) and liquid-assisted grinding (LAG) conditions in a ball mill [51]. Insight into the dynamics of the formation of reaction intermediates and products was obtained by in situ Raman monitoring that provided information on the nature of the catalytically active PdII

• azobenzene with NXS and Pd(OAc)2 as precatalyst in the presence of TsOH and MeCN as solid and liquid additives, respectively, led to the ortho-halogenated products relative to the azo group of the azobenzenes. In situ Raman monitoring of these reactions confirmed that the most favorable reaction pathway is

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• the construction of diverse carbocyclic systems [17][18][19][20][21][22][23][24]. In these reactions, the tertiary phosphine firstly adds to electron-deficient alkenes, alkynes, and allenes to give active ionic intermediates. Then, the in situ-generated ionic intermediates further react with various

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• final catalyst. In the next step, a transition-metal-ion based catalyst was prepared in situ by addition of one equiv of [Rh(acac)(CO)2], which generated the monoligated rhodium complex. Finally, catalysis was carried out at 5 bar of H2/CO (1:1) that converted the [Rh(acac)(CO)2] complex into the active

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

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

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• corresponding α-hydroxy-1,2-diketone formed in situ as a result of the photoreaction. As shown above, only the phototransformation of the allomaltol fragment occurs under UV irradiation of pyrazoles 12a–l, while the 6π-electrocyclization of the hexatriene system is not observed. Based on this fact we assumed

• , labile substituted α-hydroxy-1,2-diketones can be obtained. For the first time the possibility of isolation of the final α-hydroxy-1,2-diketone in pure form was demonstrated in the case of 14a. We proposed the approach for trapping of unstable α-hydroxy-1,2-diketones in situ employing the condensation

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• was commonly introduced through in-situ, noncovalent inclusion/encapsulation in the cavity or by covalent, post-functionalization of the macrocyclic scaffold. The encapsulated catalytic group could occupy the space for substrate entering, or has a risk to be squeezed out of the cavity under complex

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• -unsaturated ketones [29]. Using this method, we developed the in situ reduction of 3-phenacylideneoxindoles by tosylhydrazine and sequential Micheal addition/cyclization with another molecule of 3-phenacylideneoxindole towards bisspirocyclopentenebisoxindole derivatives. Although Shanthi et al. [30] reported

• dispirocyclopentanebisoxindole 3j. Therefore, we can conclude that 3-phenacylindolinone is in situ generated in the reaction medium from reduction of 3-phenacylidieneoxindole by tosylhydrazine, which undergoes cyclodimerization with another equivalent of 3-phenacylidieneoxindole under base-catalyzed conditions. This study also

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• Discussion The reason why we investigated the reaction under mild basic conditions was because nitrile oxides are often generated by dehalogenation of hydroximoyl chlorides in situ under basic conditions or by dehydration of nitroalkanes [30]. So we were wondering whether we could take advantage of that

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• with phenols in the presence of Cs2CO3/DMF affords α-phenoxy-α’-hydroxyketones (1:1 adducts) and α,α-diphenoxyketones (1:2 adducts) in up to 92% and 24% yields, respectively. Both products are formed via ring opening of the same intermediates, 1,3-dioxolan-2-ones, generated in situ from

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

• yield was only 10%, but after the addition of MTO and acetic anhydride, the yield increased to 46% (Table 1, entry 5) [51]. The authors suggested two simultaneous reaction pathways: a direct oxidation by rhenium bisperoxo complex and an MTO-catalyzed in situ generation of peroxyacetic acid as oxidant

• the reaction of menadione (10) with formaldehyde in the presence of gaseous HCl bubbled into the reaction medium [129][130]. Then, the chloromethyl derivative 84 was treated with diselenides, generated in situ from the reaction between Se0, NaBH4 and different acid chlorides, to form conjugates 86 in

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• prefunctionalization and deprotection synthetic procedures. Based on the logical concept of protecting groups, noncovalent interactions can be considered, because they can be built up in situ and are weak enough to let the substrate dissociate from the “protecting template” easily, omitting the complicated

• hydrogenation reaction mediated by a supramolecular catalyst was reported by Raymond, Bergman and Toste in 2019 (Figure 7) [64]. In this example, the supramolecular catalyst was prepared in situ by mixing a rhodium complex with the Ga4L612− cage host G, which had a relatively larger size with pyrene-walled

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• Scheme 2, which likely starts from the catalytic generation, in our experimental conditions, of the borylcopper(II) species A. Such copper complex proved to be not isolable, but could be easily generated in situ and may act as a genuine Cu(II) catalyst, with a labile coordination site [30]. According to

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• assigned as 1-alkyl-3,5,5-trimethyl-5,6-dihydro-1H-azepino[4,3,2-cd]indoles 8. The authors proposed that aza-Michael addition of 4-aminoindoles 7 to in situ generated mesityl oxide gives compound 9 which undergoes a regioselective intramolecular cyclization–dehydration sequence to furnish 8. In 2019, Zou

• ]indolylvincoside 12 (de = 85%) [14]. In situ lactamization of 12 under basic conditions (10% Na2CO3) generated stable polycyclic compound 13 in 70% yield (Scheme 5A). In a separate report published in 2020, the same research group disclosed that water could act as both catalyst and solvent in the Pictet−Spengler

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• , Balla and co-workers discussed the scope of the reaction by the utilization of in-situ generated α-Fe2O3 nanoparticles with several activated and unactivated halides (Scheme 13) [30]. They also examined the effect of concentration of fluorescent aggregates of HPB, i.e., the size of the generated

• nanorods was found to increase with respect to Fe3+ ions-to-ligand ratio and vice versa. The reusability and separation of the ferromagnetic α-Fe2O3 nanoparticle catalyst were very effective, simple and economical due to its magnetic nature. The in situ-generated α-Fe2O3 nanoparticles showed better

• Sonogashira coupling reaction and the catalyst. A mechanism was also suggested where this in situ formed colloidal layer acts as the anchoring agent (Scheme 37). Conclusion The Sonogashira reaction is an important coupling reaction in organic chemistry. Even though most of the reactions are well explored by

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• 20 mol % excess of the terminal alkynes in a mixture of solvents (DMF/H2O 4:1) at 60 °C and Cu(I) generated in situ [33], but in catalytic amount. This approach resulted in the synthesis of eight 1,4-disubstituted 1,2,3-triazole derivatives (2a–h) in good yields (45–78%) and high purity. Other two