Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• , leading to different cyclization products such as pyrrolines 53 and pyrrolones 51, respectively. The procedure was also extended to Passerini adducts to afford butenolide structures 52 after the post-cyclization process [107]. In all the cases described above, the ester group of glyoxylate remains in the

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• very little influence in the enantiomeric ratios, although electron-donating groups performed slightly better in terms of yield, as observed before for the N-Boc-protected pyrrolines. Weak electron-donating groups such as the methyl group furnished compound 4bj in a higher yield and good er. Carbonyl

• chromatography (HPLC) analysis of the purified compounds. Heck–Matsuda reaction of the protected 2,5-dihydro-1H-pyrrole with Ns and 2-Ns groups (pyrrolines 1c, 1d). Reaction conditions: 1) pyrroline 1c or 1d (0.30 mmol, 1.0 equiv), aryldiazonium salts 2 (0.60 mmol, 2.0 equiv), Pd(TFA)2 (5 mol %), L1 (6 mol

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• -thiolated pyrroles 61 and pyrrolines 62 from propargylic tosylamides 60 and N-thiosuccinimides 1 was described by Gao′s group (Scheme 25) [61]. When AlCl3 as the Lewis acid catalyst and nitromethane as the solvent were used, a series of 3-thiolated pyrrole products 61 were detected, and 3-thiolated

• pyrrolines 62 were obtained by changing the reaction solvent to MeCN. Also, organic fluorophore compounds such as benzothienopyrrole and bis-thiolated boron dipyrromethene can be achieved from 3-thiolated pyrroles. Mechanistic studies showed that the oxidative species HNO and HCHO were generated through a

• cyclization of β,γ-unsaturated oximes with N-(arylthio)succinimide. Synthesis of 4-chalcogenyl pyrazoles via chalcogenation/cyclization of α,β-alkynic hydrazones. Controllable synthesis of 3-thiolated pyrroles and pyrrolines. Possible mechanism for controllable synthesis of 3-thiolated pyrroles and pyrrolines

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• tandem reaction of 2-trifluoromethyl-1,3-enynes 36 with primary amines, affording various trifluoromethyl-substituted 3-pyrrolines [56]. Subsequently, they also developed a novel route for the synthesis of halogenated trifluoromethylated pyrroles 37 and 38 by sequential intermolecular hydroamination

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

• ). Cyclizations involving a position in the attacking nucleophile The reaction of ethyl 4-bromocrotonate (81) with LDA at −78 °C and subsequent addition of chiral imines 14 afforded 3-pyrrolines 82 with high diastereoselectivity. Chogii and Njardarson proposed that after deprotonation of 81, the resulting

• -pyrrolines 82 were formed as single diastereomers [101]. The whole process could be considered a [3 + 2] annulation, and aziridines were not observed as competing reaction products (see above Scheme 11). In addition, hindered imines, ethers, sulfonates, heteroaryl substituents, and conjugated imines were all

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• , namely a Brønsted acid-activated hydroxypyrroline, depend on the reaction conditions and the structure of the hydrazides. Keywords: hydrazides; pyridazines; pyrrolines; recyclization; ring expansion; Introduction Di- and tetrahydropyridazines are valuable heterocyclic motifs which are utilized as key

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• oximes 27.1 can be used to efficiently generate an iminyl radical in the presence of eosin Y (OD13, Scheme 27) [140]. This methodology was employed in hydroimination and iminohydroxylation cyclization reactions to give the pyrrolines 27.2. The transformation proceeds via a SET reduction of the electron

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• catalyst 7. Pyrrolines were produced in excellent yields by RRM of sulfonamides 31a,b using the catalyst 2 under dichloromethane reflux conditions (32a 99%, 32b 70%) (Scheme 3). Five-membered heterocycles such as 34 and a seven membered heterocycle 35 in 40:60 ratio (97%) were formed by RRM of

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolcular [1,5]-hydride shift/isomerization reaction has been realized, using the inherent reducing power of 3-pyrrolines. A series of N-arylpyrrole containing amines are obtained in high yields. Keywords

• part of our interest in expanding the inherent reducing power of 3-pyrrolines, we report herein the Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes using the iminium group as the H-shift acceptor (Scheme 1, reaction 3). Notably, this reaction should meet the

• /isomerization reactions that utilize the inherent reducing power of 3-pyrrolines are underway in our laboratory. Experimental General procedure for the preparation of N-arylpyrroles 3: A mixture of benzaldehyde 1 (0.3–0.5 mmol), amine 2 (1.2 equiv) and ZnCl2 (5 mol %) were stirred in dichloromethane or DCE (5.0

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• substrate scope was, however, very limited. 2.2 [3 + 2] Annulations of allenes with activated imines Phosphine-catalyzed [3 + 2] annulation of allenes with activated imines has emerged as an important tool for the synthesis of functionalized pyrrolines, which are valuable heterocyclic compounds for the

• [64][65], the former reactions generated pyrrolines with good ee (73–88%), albeit with moderate yields (25–74%) [64]. The relative ease of removal of the diphenylphosphinoyl (DPP) protecting group makes this reaction quite valuable as an organic transformation for the preparation of secondary

• pyrrolines. The latter reactions (Scheme 31) required harsh conditions, leading to pyrroline derivatives in low yields with moderate ee [65]. In terms of both conversion and enantioselectivity, binaphthyl skeleton-based cyclic chiral phosphines are not ideal catalysts for asymmetric [3 + 2] annulations of

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• peptides 36 and 37 (Scheme 12). In this work, no limitations regarding the type of isocyanide inputs were observed. Several alkyl-, aryl- and ester-substituted isocyanides gave the desired products. On the other hand, aryl-substituted pyrrolines as the imine input proved less efficient. The authors argued

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• transition structures associated with the formation of C2–Cα and C5–Cβ bonds (TS11exo, TS11ent and TS11endo) correspond to concerted but highly asynchronous cycloadditions. On the other hand, TS12 is associated with a stepwise mechanism. As possible applications of the resulting pyrrolines 7aa, it was

• needed using other synthetic strategies [43]. Pyrrolines also possess a typical 1,3-dipole precursor structure (azomethine ylide), so a second cycloaddition was attempted with a new equivalent of N-methylmaleimide. The reaction took place under microwave assisted heating (1 h, 75 W) using triethylamine

Synthesis of enones, pyrazolines and pyrrolines with gem-difluoroalkyl side chains

• Assaad Nasr El Dine,
• Ali Khalaf,
• Danielle Grée,
• Olivier Tasseau,
• Fares Fares,
• Nada Jaber,
• Philippe Lesot,
• Ali Hachem and
• René Grée

Beilstein J. Org. Chem. 2013, 9, 1943–1948, doi:10.3762/bjoc.9.230

• -mediated isomerisation affords enones in fair yields with a gem-difluoroalkyl chain. These derivatives were used to prepare pyrazolines and pyrrolines with the desired gem-difluoroalkyl side chain by cyclocondensations in good yields and with excellent stereoselectivity. A one-pot process was also

• ; palladium catalysis; pyrazolines; pyrrolines; Introduction A widely used strategy in bioorganic, medicinal chemistry and in chemical biology is the selected introduction of fluorine in organic molecules since it strongly modifies their properties [1][2][3][4][5][6][7][8][9]. On the other hand, heterocyclic

• of Shibata has developed an elegant organocatalyzed asymmetric approach to such pyrrolines [33]. Moreover, an efficient synthesis of β-trifluoromethylated Δ1-pyrrolines has been reported [34]. Therefore, we selected pyrrolines with CF2R side chains as a second example of 5-membered heterocyclic

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• the mixtures could not be readily separated by column chromatography, diastereomeric ratios were determined by 1H NMR and were advanced without further purification. Reaction of allene 6 under the silver-nitrate-mediated cyclization conditions afforded the desired fused pyrrolines 1. However, in the

• initial phases of this cyclization process, a color change was noted during the purification process. Indeed, when NMR stability studies were performed on the syn- and anti-pyrrolines 1{5}, decomposition of both diastereomers was evident. Although it was generally difficult to isolate the individual

• (Table 1, entries 8–15). While in some cases the intermediate pyrrolines 1 were observed (Table 1, entries 8, 10, 14, 15), the corresponding tosylated products were not obtained. The heteroaromatic examples (Table 1, entries 9, 11–13), did not undergo cyclization upon treatment with silver nitrate. For

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines

• Luca Banfi,
• Andrea Basso,
• Valentina Cerulli,
• Valeria Rocca and
• Renata Riva

Beilstein J. Org. Chem. 2011, 7, 976–979, doi:10.3762/bjoc.7.109

• with a few types of chiral substrates [9][10][11][12][13][14][15]. In most cases these are represented by five-membered imines (pyrrolines) with a stereogenic centre α to the imine carbon (1,2-induction), although this relative arrangement is not a guarantee of good stereoselectivity [8][14][16

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

• Satish S. More,
• T. Krishna Mohan,
• Y. Sateesh Kumar,
• U. K. Syam Kumar and
• Navin B. Patel

Beilstein J. Org. Chem. 2011, 7, 831–838, doi:10.3762/bjoc.7.95

• -[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters in very good to excellent yields under mild reaction conditions. The electronic and steric impact of the substituents on the kinetics of ring expansion of N-vinyl aziridines to pyrrolines has been studied. Various diversely

• substituted novel pyrroline derivatives have been synthesized by this methodology and the products can be used as key intermediates in the synthesis of substituted pyrrolines, pyrroles and pyrrolidines. Keywords: 5-alkyl/aryl/heteroaryl substituted 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates; aziridine; N

• ], pyrrolines [10][11][12][13][14], imidazolidinones [15], β-lactams [16][17][18] and azepines [19][20][21]. There is ample evidence in the literature to confirm that the syntheses and applications of the N-acyl, N-sulfonamide or N-benzyl protected C-vinylaziridines are of considerable interest in organic

Knorr- Rabe partial reduction of pyrroles: Application to the synthesis of indolizidine alkaloids

• Brendon S. Gourlay,
• John H. Ryan and
• Jason A. Smith

Beilstein J. Org. Chem. 2008, 4, No. 3, doi:10.1186/1860-5397-4-3

• does not occur readily. However, dissolving metal reduction with zinc under acidic conditions gives 3-pyrrolines (2,5-dihydropyrroles) in reasonable yield. This dissolving metal reduction was first reported by Knorr and Rabe in 1901 but since then has only been reported for the reduction of electron

• electron density of the heterocycle such that reasonable yields of the 3-pyrrolines are obtained [3]. This method was recently exploited for the elegant synthesis of the pyrrolidine alkaloid (±)-1-epiaustraline (3) (Scheme 1) [4]. During our studies towards the synthesis of indolizidine alkaloids we

• required bicyclic 3-pyrrolines and chose to explore accessing these intermediates via partial reduction of the corresponding pyrrole derivatives. These substrates were far more electron rich than those of Donohoe and thus not amenable to Birch reduction methodology. Therefore, we turned to an underutilised