Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• -Trisubstituted pyrrolidine-2,3-dione derivatives were prepared from the above mentioned 2-pyrrolidinone derivatives and aliphatic amines, which exist in enamine form and are stabilized by an intramolecular hydrogen bond. A possible reaction mechanism between 3-pyrroline-2-one and aliphatic amine (CH3NH2) was

• . Keywords: 4-acetyl-3-hydroxy-3-pyrroline-2-ones; 1,5-dihydro-2H-pyrrol-2-ones; pyrrolidine-2,3-dione; 2-pyrrolidinone derivative; 3-pyrroline-2-one; Introduction 2-Pyrrolidone, also known as γ-lactam, is a five-membered heterocyclic ring containing four carbon and one nitrogen atoms [1]. This γ-lactam

• form doxapram hydrochloride which helps to increase the respiratory rate [7] (Figure 1). Among the 2-pyrrolidinone derivatives, 1,5-dihydro-2H-pyrrol-2-ones, also named as 3-pyrrolin-2-ones, are important builiding blocks which can be further modified in organic synthesis and medicinal chemistry [8][9

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

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• γ-lactam scaffold [40][41][42][43][44]. The pyrrolidinone fragment is often synthesized by transition metal- [45][46][47][48][49][50] or Lewis acid-catalyzed cyclization reactions [51][52][53][54]. The Diels–Alder reaction can also be used for the preparation of functionalized γ-lactams in a single

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• the γ-position [37][39][40]. An examination of the allenamide unit under these conditions is shown in Scheme 4, and the six allenylamides/sulfonamides (15, 21–25) were prepared using known conditions [52][53]. The allenamides derived from pyrrolidinone (21), piperidinone (22) and oxazolidinone (15

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• derivatives 287–291 [78] (Scheme 52). In 1988, Kanaoka et al. studied the photochemistry of semicyclic and acyclic thioimides 292–294 and 295 with 2,3-dimethylbut-2-ene (215a) afforded the corresponding thietanes 296–299. However, the products were obtained together with pyrrolidinone, thiopyrrolidinone, or

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• (PMP)), and solvents (N,N-dimethylacetamide (DMA), 1,3-dimethyl-2-imidazolidinone (DMI), N-methyl-2-pyrrolidinone (NMP), tetrahydrofuran (THF), 1,4-dioxane, ethanol, methanol, acetonitrile, and toluene) together with aryl iodides and other reagents were purchased from commercial sources (namely J&K

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• diethylzinc (Scheme 20) [49]. Although the Michael acceptor bearing the N-acyloxazolidinone moiety that was successfully used by Hoveyda (95% ee) gave a lower enantioselectivity (64%), a more satisfactory enantiocontrol was obtained with the substrate having a 2-pyrrolidinone fragment (87% ee). The scope was

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• functionalization reactions. Aryl C–H fluorination with various directing groups: With Pd(OTf)2(MeCN)4 and N-methyl-2-pyrrolidinone (NMP) used as the catalyst system, in 2011 the Yu group [57] described the ortho-fluorination of benzoic acid substrates with a directing group, an electron-deficient removable acidic

Ring-opening metathesis of some strained bicyclic systems; stereocontrolled access to diolefinated saturated heterocycles with multiple stereogenic centers

• Zsanett Benke,
• Melinda Nonn,
• Márton Kardos,
• Santos Fustero and
• Loránd Kiss

Beilstein J. Org. Chem. 2018, 14, 2698–2707, doi:10.3762/bjoc.14.247

• ethylene atmosphere of bridged pyrrolidinone (±)-18 took place at 20 °C and afforded the corresponding divinylated lactam (±)-19 [31][32]. Somewhat surprisingly, in contrast to model derivatives used previously, the highest yield (70%) was attained with first generation catalyst HG-1 (5 mol %). In the

• presence of the second generation catalysts, in turn, the ring-opened pyrrolidinone derivative (±)-19 could be isolated only in low yields (Scheme 7, Table 5). As observed, the ROM reactions of the investigated unsaturated cyclic substrates (namely (±)-3, (±)-4, (±)-9, (±)-14, (±)-16 and (±)-18) gave

• precursors for the preparation of amino acids and amino esters [21][22]. When compound (±)-19 was subjected to either acid-catalyzed hydrolysis or ethanolysis at reflux, it furnished a pyrrolidinone derivative identified as (±)-23, instead of the expected product (amino acids or amino ester) formed via the

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• acid A analogue containing the tetramic acid moiety in place of the 2,3-pyrrolidinone ring (compound 1), while maintaining unchanged all the other structural features of the natural compound. The advantage of this substitution should be a higher stability of the heterocyclic ring, hopefully coupled

• -pyrrolidinone analogue of the natural compound leopolic acid A, by a convergent synthetic strategy. Compound 1 is more effective than the parent leopolic acid A against Staphylococcus pseudintermedius and E. coli strains (MIC 8 µg/mL and 64 µg/mL, respectively) and Staphylococcus pseudintermedius strains

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• –87% yields (Scheme 32) [2][42]. Similarly, Hewson and co-workers synthesized bicyclic 2-pyrrolidinone derivatives 48 from 5-acetyl-2-pyrrolidinone in a yield of 40–68% (Scheme 33) [48]. In 1994 Burley and Hewson reported a reaction of vinylphosphonium salt with nitrogen nucleophiles, obtained by

• -pyrrolocarbaldehyde. Stereoselective synthesis of bicyclic 2-pyrrolidinone derivatives in the reaction of vinylphosphonium halides and 5-acetyl-2-pyrrolidinone. Stereoselective synthesis of 3-pyrroline derivatives in the intramolecular Wittig reaction from vinylphosphonium salts and nitrogen nucleophiles. Synthesis

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• , Eötvös utca 6, H-6720 Szeged, Hungary 10.3762/bjoc.12.247 Abstract Starting from racemic naringenin ((±)-1), a mixture of dracocephin A stereoisomers 6-(2”-pyrrolidinone-5”-yl)naringenin (±)-2a–d and its regioisomer, dracocephin B 8-(2”-pyrrolidinone-5”-yl)naringenin (±)-3a–d originally isolated from

• groups anchored the orientation of the pyrrolidinone moiety. The two conformers differed in the orientation of the two 4’-OH and the C-2 aryl moiety adopted equatorial orientation with M helicity and envelope conformation of the condensed heteroring. The calculated Boltzmann-averaged ECD spectra of (2R,5

• separated by chiral HPLC and their stereochemistry was studied by TDDFT-ECD calculations. By testing different methods for the calculation of conformers and ECD, the configurational assignment of C-2 of the flavanone moiety could be confirmed, while the C-5” of the pyrrolidinone unit could not be assigned

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• indolizidinone [31]. Several synthetic procedures have also been developed for the preparation of tashiromine or epitashiromine enantiomers. (+)-Tashiromine has been synthetized from a pyrrolidinone derivative through chiral Lewis acid-catalysed cyclization to substituted pyrrolidinones [17], by the

• intramolecular cyclization of a chiral alkenylated pyrrolidinone, followed by hydroxylation [32], or by the intramolecular ring closure of chiral pyrrolidine diesters followed by ester and oxo group reduction [33], while the syntheses of (+)-epitashiromine starts from a chiral morpholine derivative, with nitrone

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• 10 was accomplished by first demethylating 2-acetyl-6-methoxynaphthalene (5) with thiophenol and 0.1 mol percent potassium carbonate in N-methyl-2-pyrrolidinone at 194 °C [19] to generate the hydroxynaphthalene 6 (72%) followed by protecting the hydroxy group with TBSCl to give 7 (89%, Scheme 1A). α

• , 24 and 27 (acetate ester). Previously studied caged diethyl phosphate PPGs possessing aromatic (benzyl, phenacyl, and naphthylmethyl) phosphates. Synthesis of 2,6-HNA DEP (10), 1,4-HNA DEP (14a), and 1,4-MNA DEP (14b) DEP esters. Reagents and conditions: a) PhSH, K2CO3, N-methyl-2-pyrrolidinone, 194

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• ’-tetramethyluronium tetrafluoroborate, 1-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone (Sigma-Aldrich, USA); Boc-Gly-PAM resin (substitution 0.76 mmol/g, NovaBiochem, Germany); sodium azide, glycine (Serva, Germany); sodium periodate, bromotrichloromethane, di-tert-butyl dicarbonate (Acros Organics, USA

From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• substitution was promoted by microwave irradiation in N-methyl-2-pyrrolidinone. Attempts to remove the benzyl groups of the phosphoramidate moiety by hydrogenolysis with 10% Pd/C led to the cleavage of the P–N bond and the reduction of the macrocycle to hydroporphyrin-type derivatives. The extent of the effect

• , rendering the method inadequate. Thus, we performed the reaction by microwave irradiation witth a solution of TPPF20 and the primary aminoalkyl dibenzylphosphoramidates in N-methyl-2-pyrrolidinone (NMP) as the solvent [9]. The conversion into the new porphyrin monoaminoalkyldibenzylphosphoramidate

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• : benzothiazole; domino reaction; electron-deficient alkyne; multicomponent reaction; pyrrolidinone; Introduction Over fifty years ago, Huisgen firstly described the addition reactions of nitrogen-containing heterocycles to electron-deficient alkynes to form 1,4-dipolar intermediates, which can reacted

• 50–60 °C for about 48 hours. In this reaction the excess piperidine acted as base catalyst. After work-up, the expected polyfunctionalized 2-pyrrolidinone 1a was obtained in good yield (Table 1, entry 1). Under similar reaction conditions, various aromatic aldehydes were utilized in the reaction to

• give the polyfunctionalized 2-pyrrolidinone 1b–1f (Table 1, entries 2–6) in 53–72% yields, respectively. The four-component reaction containing diethyl acetylenedicarboxylate also successfully afforded the expected 2-pyrrolidinone 1g in 63% (Table 1, entry 7). In view of the success of the above

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• enantiopure α and β-aminoynones was successfully used in our group to access pyrrolidinone and pyridone heterocycles via a gold-mediated approach [19][20]. The use of β-aminoynone intermediates for the synthesis of 2,3-dihydropyridones was recently developed by Georg [21] (Scheme 1). This strategy involves

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• [25], pyrrolidinone [26], pyrrolidine [27] and piperazine [28], to the porphyrin periphery. In addition, many porphyrin dimers and trimers have displayed significant biological efficacy [29] and some of these are used as photosensitizers in PDT applications for the treatment of various types of

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• solvent for all the couplings except for Fmoc-Phe-OH and Fmoc-D-Phe-OH, which were coupled in N-methyl-2-pyrrolidinone (NMP). Each coupling step was repeated twice. The Fmoc group was removed by treating the resin with piperidine/DMF (2:3, 3 min) followed by two treatments of piperidine/DMF (1:4, 12 + 15

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• ) [114]. 5.4. Parson. Radical cyclization The development of novel cascade (or domino) radical reactions is an active area of current research, and one approach to the mitomycin ring system focused on the application of 1-6-hydrogen atom transfer to create a pyrrolidinone radical, which could then

• isolated. This route allowed a convergent approach to the mitomycins via a tandem radical cyclisation process. It also provided an elegant approach to an intermediate pyrrolidinone radical, which proved impossible to access from a classical halogen-atom transfer route because of the difficulty in preparing

Reactions of glycidyl derivatives with ambident nucleophiles; part 2: amino acid derivatives

• Gerald Dyker,
• Andreas Thöne and
• Gerald Henkel

Beilstein J. Org. Chem. 2007, 3, No. 28, doi:10.1186/1860-5397-3-28

• substrates will be sufficiently understood. Structure of oxidation product 10a in the crystal. Planned construction for morpholinones 3 from amino acid and glycidyl derivatives 1 and 2. R1, R3 = H, Alkyl, Aryl; R2 = H, Acyl; X = leaving group: Cl, Br, I, p-OTs. Synthesis of pyrrolidinone-fused heterocycles