Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• ) was necessary since at higher concentrations, the nickel catalyst would not dissolve completely. By increasing the amount of 141, the yield gradually increased, so that 5 equivalents of N-Boc-pyrrolidine (141) were used, prolonging the irradiation time to 60 h, to achieve a yield of 88%. Other nickel

• pyrrolidine 141 was also possible employing a variety of alkyl bromides, including cyclic and acyclic secondary alkyl bromides as well as alkyl bromides carrying functional groups such as organosilyl and boronate moieties. However, the solvent had to be changed from acetone to acetonitrile in order to achieve

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• synthesized starting from ʟ-methionine. The subsequent enyne ring-closing metathesis in the presence of the Grubbs first-generation catalyst (5 mol %) afforded a pyrrolidine derivative in 76% yield (Scheme 12). This pyrrolidine was converted into a pyrrolo-1,4-benzodiazepinone bearing a vinyl side group

• in the pyrrolidine ring catalyzed by RhCl3·H2O, followed by debenzylation, amidation, and aminal generation using the Stille protocol [77]. (–)‐Clavukerin A and related sesquiterpenes Applying original organocatalytic/metal-catalyzed tactics, Metz et al. [78] reported a tandem dienyne RCM for the

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• chemistry [2][3][4]. Notably, one of these nitrogen-containing heterocycles is tetramic acid which contains a pyrrolidine-2,4-dione moiety. Many natural products have this key structure moiety (Figure 1) [5][6][7]. Because of their active cyclic keto-enol structure, the heterocyclic tetramic acid compounds

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• 9,9-dihydro-5-silafluorene (2f), which gave the spiro-type phenoxasilin 3f in 96% yield. We then investigated the scope of the starting biaryl ethers used in the reaction as well as related derivatives thereof using dihydrodiphenylsilane (2a, Scheme 3). Pyrrolidine-substituted diaryl ether 1b was

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• possessing a Z geometry, as evinced by a NOE interaction between Hd and the methyl group. The cis relationship between the OH group and the pyrrolidine ring, resulting from the chemo- and stereoselective syn reduction of the carbonyl group, was evinced by NOESY-1D experiments showing intense NOE effects

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• Mitsunobu conditions led exclusively to the pyrrolidine derivative (76%) [32]. Therefore, the few literature examples reported until now are either complicated by side reactions or involve long reaction times and/or modest yields. Polyphosphoric acid (PPA) esters PPE (ethyl polyphosphate) and PPSE

Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?

• Dominika Krištofíková,
• Juraj Filo,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290

• )-1-(pyrrolidin-2-ylmethyl)pyrrolidine did not proceed at all. Of note, the bases used in these Ireland–Claisen rearrangements did not affect the diastereoselectivity and the syn/anti ratio was approximately 70:30 in all cases. The Ireland–Claisen rearrangement of allyl propionate (1a) with Et3N and

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• ). Electron-poor (F and Cl) and electron-rich moieties (methoxy and pyrrolidine abbreviated as OMe and Pyr, respectively) were considered to analyze the effect of these ortho-groups on the thermal stability of Z-arylazopyrazoles (Table 1). Such substitution has proved useful in the improvement of azobenzene

• (Table 1). In contrast, chloro-substituted analogues present a significant decrease in the computed half-lives: 90 days for 4pzH-Cl1 and 5 days for 4pzH-Cl2. The inclusion of methoxy and pyrrolidine groups in the ortho-position leads to an enhanced Z-isomer thermal stability compared to unsubstituted

• 4pzH, with t1/2 = 2000 and 15000 days for 4pzH-OMe1 and 4pzH-OMe2, respectively, and 34000 days for 4pzH-Pyr1 (Table 1). Unexpectedly, the inclusion of two bulky pyrrolidine groups in ortho (4pzH-Pyr2) leads to a decrease in t1/2 (76 days). For the arylazopyrazole scaffold 4pzMe, in line with the trend

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• carbonyl compounds for the synthesis of heterocyclic compounds has been repeatedly demonstrated [2][3]. We recently used a domino reaction of amino acid, ketone and dimethyl fumarate for the one-pot synthesis of a substituted pyrrolidine, which then was converted into a reduction-resistant pyrrolidine

• -tetrasubstituted-3,4-bis(methoxycarbonyl)pyrrolidine ring. The 1H signal at 3.19 ppm shows a cross peak with an atom of a fully substituted C=C moiety, while another lower field signal of a CH group at 3.44 ppm interacts with a CH-group carbon at 55.1 ppm. The hydrogen of the latter group shows cross peaks with

• , relaxation of a spirocyclohexane-substituted nitroxide [10] is also shown in Figure 5. The Tm vs T dependence generally shows consistent trends in frozen solutions. For 2,5-tetramethyl-substituted pyrrolidine and piperidine nitroxides, a local maximum appears in their phase relaxation (1/Tm) at T > 100 K as

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• 630090, Russian Federation Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, Institutskaya 3, Novosibirsk 630090, Russian Federation 10.3762/bjoc.15.200 Abstract Sterically shielded nitroxides of the pyrrolidine series have shown the highest resistance to reduction. Here we report the

• synthesis of new pyrrolidine nitroxides from 5,5-dialkyl-1-pyrroline N-oxides via the introduction of a pent-4-enyl group to the nitrone carbon followed by an intramolecular 1,3-dipolar cycloaddition reaction and isoxazolidine ring opening. The kinetics of reduction of the new nitroxides with ascorbate were

• studied and compared to those of previously published (1S,2R,3′S,4′S,5′S,2″R)-dispiro[(2-hydroxymethyl)cyclopentan-1,2′-(3′,4′-di-tert-butoxy)pyrrolidine-5′,1″-(2″-hydroxymethyl)cyclopentane]-1′-oxyl (1). Keywords: aldonitrone; 1,3-dipolar cycloaddition; pyrrolidine nitroxides; 1-pyrroline-N-oxide

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• conditions and delivered the corresponding products in good yields (7b–d). Even a heterocyclic amine such as benzo[d]thiazol-2-amine and a cyclic amine like pyrrolidine also reacted well and produced the corresponding amides in decent yields (7e and 7f). Control experiments In order to elucidate the reaction

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• selective desilylation and N-debenzylation with simultaneous N-Boc protection and served as a key intermediate for installation of a dimethylhexylene fragment in Julia–Kocienski olefination [56]. Pyrrolidine alkaloids (−)-hygrine ((S)-61) and (−)-hygroline ((2S,2'S)-62) were isolated from many natural

• ]pyrrolidin-1-yl group [64]. The synthesis of the corresponding pyrrolidine (3S,3'R)-68 began from the aziridine (E)-acrylate (2R,1'S)-69a (Scheme 18) readily prepared from the aldehyde (2S,1'S)-6 [31]. Michael addition of nitromethane to the acrylate (2R,1'S)-69a gave an inseparable mixture (70:30) of

• aziridine esters 70 which were subjected to a selective reduction of the nitro group to afford the major pyrrolidine-2-one (2R,4'R,1''S)-71 after chromatographic purification [65]. The reduction of the amide bond gave (2R,3'R,1''S)-72 thus providing a cyclic part of (3S,3'R)-68. The transformation of the

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• ]. Table 1 summarizes the differences observed in the studied cases. The presence of a heteroatom contributes to lower the energy barrier of the oxidation reaction, and in the case of the pyrrolidine, it is below the reactant, demonstrating the stabilizing effect of the heteroatom in the transition

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• could be converted to other derivatives by Suzuki–Miyaura coupling, reduction or oxidation reactions. Keywords: azomethine ylide; cycloaddition; heterocycle; pyrrolidine; stereoselective; Introduction Cycloaddition reactions of azomethine ylides are an important class of pericyclic reactions that give

• rise to pyrrolidine rings, prevalent in a large number of natural products and bioactive compounds. Many methods have been used to prepare azomethine ylides that undergo cycloaddition with π-systems, especially electron-poor alkenes to give pyrrolidine products [1][2][3][4]. Azomethine ylides can be

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• ) – derived from a renewable resource like sugar cane biomass – for the incorporation of chiral pyrrolidine-based motifs capable to catalyze relevant asymmetric reactions. The incorporation of an organocatalyst into a polymer support requires either conjugation to the polymer or functionalization with a

• ) due to the lack of the catalytic pyrrolidine moiety. On the other hand, PFA-supported catalysts 3 and 4 gave moderate to good yields depending on the solvent used. In general, polymeric catalyst 3 provided a better yield, enantio- and diastereoselectivity in the Michael adduct than 4 in all tested

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• most of the cases, the Z-isomer as the sole or main product, while tert-butyl derivatives gave the E-isomer selectively. On the secondary amine side, morpholine, piperidine, pyrrolidine and dibutylamine all rendered the reaction efficiently. A plausible explanation for the mechanism of this

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• NH, OH and methyl groups of the dioxanedione cycle are absent in the 1H NMR spectra of trifluoroacetates 9. The broad signal of the NH2 group shifts to the downfield signal of NH3+ at 8.5–8.2 ppm. Protons of the СН2–СН fragment in the pyrrolidine cycle show the shifts of an ABX system for СНХ at 4.73

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• ]. The C=C double bonds are in the cyclohexene units range between 1.307–1.316(3) Å and the S=O bonds are between 1.417–1.414(3) Å. The conformation is defined by steric effects, which force a fold of the cyclohexene rings relative to the mean plane through the pyrrolidine group. For both enantiomers

• , the cyclohexene ring has a twist-boat conformation and the pyrrolidine rings are in half-chair conformation. The structures contain four asymmetric carbon atoms and the stereogenic centers are as follows: C1(R), C6(S), C11(R), and C16(S), where the N-chlorosulfonyl group attached to the carbonyl atom

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• lower enantiomeric excess (54% ee). Conversely, Shen et al. [18] performed an aldol reaction in a buffer using L- and D-proline-derived CDs connected through a pyrrolidine skeleton as catalysts and observed 94% ee. More recently, Liu et al. [19] reported the excellent enantioselectivity of 99% ee in an

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• 3.96–3.87 ppm to broad singlet at 4.60–3.95 ppm. Furthermore, a significant difference is observed also in the UV spectra. Product 8a has an additional absorption maximum at 370 nm (Figure 4). In the 7-deazapurine series the SNAr reactions between 2,6-diazido-9-methyl-7-deazapurine (3) and pyrrolidine

• (piperidine or pyrrolidine) substituents did not significantly influence fluorescent properties. The preliminary study showed that introduction of other aliphatic amines at C(2) does not significantly affect the photophysical properties of the target substances either. On the other hand, the present synthetic

• , 26.6, 22.6, 14.1 ppm; HRMS–ESI (m/z): [M + H]+ calcd for C12H17N10, 301.1632; found, 301.1646. Synthesis of 9-alkyl-6-azido-2-pyrrolidino-9H-purine or 9-alkyl-6-azido-2-piperidino-9H-purine derivatives 6a,b: 9-Alkyl-2,6-diazido-9H-purine 2 (8.3 mmol, 1.0 equiv) was dissolved in DMF (30 mL), pyrrolidine

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• with Cs2CO3 in anhydrous DMF, followed by the addition of an excess of pyrrolidine, produced urea 14f (24%) [48][49]. The moderate yield of 14f was attributed to the instability of the in situ-generated isocyanate 15f under the reaction conditions [50]. When trichloroacetamide 13f was treated with an

• excess of pyrrolidine and Cs2CO3 in bench grade (undried) DMF, the reaction followed a different pathway and delivered α-oxoacetamide 16f (58%) instead of urea 14f [48][49]. This type of transformation had already been reported [51] and interpreted by a Favorskii-type mechanism, presumably involving the

• formation of the gem-dichloro-α-lactam intermediate 17f which would undergo ring opening by nucleophilic addition of pyrrolidine followed by hydrolysis of the resulting α,α-dichloro-α-aminoacetamide 18f (Scheme 12). To access aminocyclopropanes, the hydrogenation of (arylmethylene)cyclopropane 13f was

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• ,3R)-2 involved attachment of allyl and vinyl groups to form (4R,5R)-42 which was next oxidized to diacid and finally esterified to give dimethyl ester of (2S,3R)-2 as the hydrochloride (Scheme 10) [59]. By formation of the pyrrolidine ring Important synthetic strategies towards 3-hydroxyglutamic

• acids take advantage of the intermediary formation of the pyrrolidine ring. Addition of the dianion of 43 to acrolein gave a 69:31 mixture of diastereoisomers with compound 44 predominating which was easily separated on silica gel. When imine 45 was treated with iodine a stereoselective

• separation the hydroxy groups in (2R,3R)-50 were protected as silyl ethers to allow oxidation at C5 to produce pyrrolidine-2-one (4R,5R)-47 (Scheme 12) which was later transformed into (2S,3R)-34 as already shown (Scheme 11) [61]. From L-malic acid (S)-Acetoxypyrrolidin-2,5-dione (51), readily available from

Degenerative xanthate transfer to olefins under visible-light photocatalysis

• Atsushi Kaga,
• Xiangyang Wu,
• Joel Yi Jie Lim,
• Hirohito Hayashi,
• Yunpeng Lu,
• Edwin K. L. Yeow and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2018, 14, 3047–3058, doi:10.3762/bjoc.14.283

• functionalized cyclopentane 3an and pyrrolidine 3ao, respectively, via 5-exo-trig radical cyclization (Table 2, entries 13 and 14). The present method was capable in functionalizing olefins 2p and 2q installed on steroid scaffolds with high efficiency (Table 2, entries 15 and 16). We next examined the reactions

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• product hamamelitannin and several of its analogues have been identified as quorum sensing inhibitors. In this paper the synthesis of pyrrolidine-based analogues of a more lead-like hamamelitannin analogue is reported. A convergent synthetic route based on a key ring-closing metathesis reaction was

• developed and delivered the pyrrolidine analogue in 17 steps in high yield. Chemoselective derivatization of the pyrrolidine nitrogen atom resulted in 6 more compounds. The synthesized compounds were evaluated in a biofilm model, but were all inactive. Keywords: hamamelitannin; iminosugar; pyrrolidine

• optimal side chain substituents are an o-chlorobenzamide on the 5-position and a non-substituted benzamide on the 2’-position. In absence of any structural information of the inhibitor–target interaction, we were interested in replacing the core tetrahydrofuran scaffold by a pyrrolidine ring in order to

The enzymes of microbial nicotine metabolism

• Paul F. Fitzpatrick

Beilstein J. Org. Chem. 2018, 14, 2295–2307, doi:10.3762/bjoc.14.204

• pyridine ring. The pyrrolidine pathway, which begins with oxidation of a carbon–nitrogen bond in the pyrrolidine ring, was subsequently characterized in a number of pseudomonads. Most recently, a hybrid pathway has been described, which incorporates the early steps in the pyridine pathway and ends with

• steps in the pyrrolidine pathway. This review summarizes the present status of our understanding of these pathways, focusing on what is known about the individual enzymes involved. Keywords: biodegradation; enzyme mechanism; flavoprotein; metabolic pathway; nicotine; Introduction The toxic alkaloid (S

• using the enzymes involved to synthesize specialty chemicals [1][2]. To date, the best-characterized bacterial pathways are those of Arthrobacter nicotinovorans and several pseudomonads. These are, respectively, known as the pyridine and pyrrolidine pathways due to the initial reactions in each. More