Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• precursors in nucleophilic allylic substitution reactions with amines, presumably due to the perceived poor leaving group ability and low reactivity of the hydroxy group. Interestingly, the direct nucleophilic substitution of the corresponding alcohols has drawn much attention because of the availability of

• derivatives in Et3N/THF mixtures [20] (Scheme 1, reaction 1, i) and acetates in THF/water [21] (Scheme 1, reaction 1, ii), or MBH alcohols in the presence of CDI (1,1’-carbonyldiimidazole) in acetonitrile (Scheme 1, reaction 1, iii) [22]. In the last case, as the hydroxy moiety is not a good leaving group

• 5a [27] as the model substrate bearing a good leaving group, with imidazole (2a, 2 equiv) as a powerful nucleophilic reagent. The reaction was achieved with no need of a catalyst or any additive in toluene at reflux affording within 24 h the SN2-type product 6a in 82% yield (Table 1, entry 1

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

• upon addition of hydrochloric acid. This is probably due to the protonation of the dimethylamino moiety or/and that dimethylamine hydrochloride is a better leaving group than the free base. The structures of compounds 6a–f were confirmed by 1H and 13C NMR spectroscopy and HRMS, as well as X-ray

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

• (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

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

• formation and a hydroxyl radical (•OH). However, it is possible to transform an alcohol into a leaving group, in the radical sense, by converting it into a halide or pseudohalide derivative [104][105]. For alcohol 8, all attempts to make a better leaving group, including phenyl sulfone derivative, to have

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

• through an intramolecular aza-Wittig reaction, yielding cyclopropane-fused 2-quinolones [2]. A nitro group not only activates substrates and stabilizes the α-anion as an electron-withdrawing group but also acts as a nucleophile, electrophile, and leaving group, exhibiting diverse reactivities [3]. For

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

• reactions involve the imidothioate IV formed via deprotonation from nitrogen (pKaN in Scheme 2). The imidothioate IV can undergo cyclization to give an energetically favorable five-membered thiazoline ring VII which then either eliminates a leaving group Y− (when Y: alkoxy, amino) or a water molecule (when

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• -electron-transfer (BET), a suitable leaving group (LG) needs to be included in one of the precursors. In this manner, reactive intermediates (e.g., radical species) may be generated in solution through the irreversible fragmentation of the substrates [15][21][22]. These intermediates eventually react 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

• and benzamides with azabenzonorbornadienes [78]. Interestingly, the dehydration step occurred smoothly with an aza-leaving group rather than the more common oxa-leaving group discussed above. In 2013, the Radhakrishnan laboratory reported the Rh-catalyzed domino ring-opening coupling reaction of

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• kinetic investigation for the EtOx polymerization showed a rather linear pseudo-first-order reaction to high monomer conversions (Figure 2a). The rate of polymerization, as one could expect, depends on the initiator (i.e. leaving group/counterion) used and MeOTf, MeOTs, EtOxMeOTf, and BnBr result in fast

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• could afford satisfying coupling yields by a suitable variation of the nature of the leaving group. In 2008, Cahiez reported an iron-catalyzed alkenylation of organomagnesium reagents with enol phosphates as electrophiles, instead of alkenyl halides [19]. In this case, when reactive enol phosphates

• RMgX:EtOMgX ratios, minor species possibly featuring alkoxide stabilized ferrous [FeII]-OEt intermediates were observed by paramagnetic 1H NMR spectroscopy. In line with this result, Fleischer and Lefèvre also recently demonstrated that the anionic thiolate leaving group EtS– released in Fukuyama cross

• benefits from the leaving group ligation at the latest stages of the cross coupling. This is particularly interesting since it can hamper the usual decomposition of the iron catalyst, which tends to afford unreactive reduced aggregates at the end of the catalytic transformation, when the coupling kinetics

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• leaving group at the 3β-position, have a unique feature in their chemical reactions. In these steroids, the breaking of the C3–X bond is facilitated by the formation of a cationic strained cyclopropane intermediate, which is formed by translocation of the C5–π bond electrons to the homoallylic carbon atom

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• solvent was removed under reduced pressure. The thus-obtained crude product (110 mg) was purified by preparative GPC using CHCl3 as eluent. Structures of chitin and chitosan oligosaccharides. Effect of the anomeric leaving group on the yield of oligosaccharides. Influence of the glycosylation temperature

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

• reagents to give versatile cyclic compounds with recovery of the tertiary phosphine [25][26][27][28][29][30][31][32][33][34]. The superior catalytic ability of tertiary phosphines was primarily attributed to their excellent nucleophilicity as a nucleophile trigger and decent cleaving ability as a leaving

• group in the catalytic process [35][36][37][38][39][40][41][42][43]. The tertiary phosphine-catalyzed reactions have been widely applied to construct diverse spirooxindole systems by using readily available isatins and 3-methyleneoxindoles as key substrates [44][45][46][47][48][49][50][51][52]. In this

Syntheses of novel pyridine-based low-molecular-weight luminogens possessing aggregation-induced emission enhancement (AIEE) properties

• Masayori Hagimori,
• Tatsusada Yoshida,
• Yasuhisa Nishimura,
• Yukiko Ogawa and
• Keitaro Tanaka

Beilstein J. Org. Chem. 2022, 18, 580–587, doi:10.3762/bjoc.18.60

• study, we used 1-methyl-4-(methylsulfanyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbonitrile (1) with a methylsulfanyl group as a good leaving group. As shown in Scheme 1, the one-pot reaction of 1 with 2-aminopyridine (2a) proceeded by refluxing in ethanol for 2 h to produce the ring-fused pyridine

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• and a hetarylhydrazine. The oxazolidine 6 was synthetized under mild reaction conditions either from nitrodiene 1 (yield 58%) or from the benzotriazolyl derivative 2c (yield 76%). The increase in yield in case of 2c supports the suggestion that the benzotriazolyl subunit is a better leaving group

• poor leaving group quality of the formal alkoxide. A conceivable mechanistic pathway for the reaction cascade to pyrazole 7 is shown in Scheme 6. Initially, a nucleophilic attack of the NH2 group of 7-chloro-4-hydrazinylquinoline on the C2 position of the oxazolidine ring of 6 leads to the formation of

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• obtained in the presence of K2CO3/CH3CN probably due to the lower reactivity of the -OAc leaving group. In case when R was a 4-NO2C6H4 group, 86% yield of the product 8a was obtained, however, in this case the Passerini product 4a (R = 4-NO2C6H4) was obtained only in 62% yield and the overall yield of

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• been studied. Similarly to isomeric triazolo[4,3-b][1,2,4,5]tetrazines [36], these derivatives do not form ipso-substitution products with the displacement of a leaving group in the tetrazine ring by the action of CH-acids. Instead, a nucleophile attack on the nitrogen atom of the tetrazine ring does

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

• anhydrides with the chloride leaving group replaced by the appropriate sulfonate leaving group, concerning sulfamoyl chlorides (ZZ'NSO2Cl) with Z and Z' being alkyl or aryl and concerning the solvolysis of chlorosulfate esters (alkoxy- or aryloxysulfonyl chlorides), with the structures ROSO2Cl or ArOSO2Cl

• some other pure or mixed solvent. The sensitivity value m is set at unity for the standard solvolysis and then for some other solvent the solvent ionizing power (Y) will be given by log (k/ko). Subsequently, with the ready availability of cage compounds (1-adamantyl and 2-adamantyl with a leaving group

• assigning the required m value for use in the two-term equation. This problem was minimized by use of the S-methyldibenzothiophenium ion MeDBTh+ (as the trifluoromethanesulfonate) as the standard substrate [39][40] (Scheme 2). This solvolysis has as the leaving group a neutral molecule, dibenzothiophene

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• compared to the more studied late TMs [39][40][41][42][43]. Besides the more recognized concept of TM cross-coupling reactions revolving around an organic electrophile bearing a leaving group and an organometallic nucleophile, there is another large area of cross-coupling reactions that have been under

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• and pinacol/semipinacol rearrangements, the 1,2-shift does not require a leaving group or carbocation intermediate, as the neighboring π system is capable of accepting the migrating group. While the reaction is generally reversible, the product can be favored through four common strategies: (1) the

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• ). Access to allylic alcohol 8 was also achievable (55%, E/Z = 56:44) in a tin-free process using a sulfonyl leaving group, via α-lithiation of sulfone 15 [18] and in the presence of LTMP (Scheme 7). γ-Hydroxysulfone 16 was formed competitively (44%, dr = 50:50), by direct addition of the lithiated sulfone

• hexane (69%, E/Z = 62:38) and the amount of dimer 24 curtailed (8%) by reducing the amount of LTMP from 2 to 1.2 equiv. The viability of a benzyl ether (Scheme 10) in the carbenoid eliminative cross-coupling offered a straightforward way to probe any effect of the size of the leaving group on

• -lithio terminal epoxides or N-Bus-aziridines with α-lithio ethers. Where 1,2-disubstituted alkenes are generated the E/Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• group is a leaving group resulting in the formation of phenanthridines is unprecedented. As is outlined in this paper we set out to investigate the scope and limitations of this reaction resulting in the formation of the phenanthridine skeleton. We also report on the application of this methodology to

• . To be effective, the desired cyclization needs a second methoxy substituent ortho- or para- to the leaving group, which in this case is an aromatic methoxy substituent. Based on these results we suggest two possible mechanisms for these transformations. Both would proceed through an intermediary

• methoxy group as a leaving group have been documented [16]. Our previous research, as shown in Scheme 1, indicated that exposure of the oxime ether 7 to UV radiation resulted in the formation of the phenanthridine 8. Attempts to synthesize the related oxime ethers from biaryl compounds 13a, 13c and 13e

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• has a remarkable structural feature: the phosphate moiety is located at the benzylic position as well as at the position α to an amide group, which makes it a good leaving group for the design and development of new reactions. Accordingly, diethyl (2-oxoindolin-3-yl) phosphates 2 have been used

• -3-yl) phosphate 2 is activated by protonation with a haloid acid. Subsequently the phosphate leaving group is eliminated to generate the carbocation intermediate III, which is then followed by rapid combination with a nucleophilic halide ion to form a 3-monohalooxindoles 3 or 4. Conclusion In