Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• reaction using xanthogenates, alkenes, and sulfonyl oxime ethers (Scheme 1, reaction 1) [21][22]. The reaction proceeds efficiently to provide good yields of α-alkoxyimino esters, potential precursors of lactams, lactones and β-keto esters. Since the three-component radical reaction involving alkyl halides

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

• tetrahydrofuran [45] have been experimentally reported as well as the oxidation of N-acylpyrrolidines to the corresponding lactams [46]. Admittedly, the oxidation of tetrahydrothiophene has been approached only computationally since in that case the sulfur atom would be more easily oxidized. Since the general

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

• methods include the efficiency in saving raw materials and working time. However, there is still a need of new catalytic systems to allow the enantioselective preparation of these heterocycles by multicomponent reactions. Keywords: indolin-2-ones; isoindolinones; γ-lactams; multicomponent reactions; 2

• , leading to final lactams 20. This mechanism is partially corroborated by the following multicomponent synthesis where benzamide 21, ortho-functionalized with a terminal alkyne group (Scheme 5), a secondary amine 22 and carbon monoxide (23) react to produce 3-methyleneisoindolinones 24 [80]. A palladium

• multicomponent reactions with amines and isocyanides by several research groups to make highly functionalized lactams. After the pioneering works by Ley [87] and Zhang [88], other contributions have been reported in the last years. For example, Shaabani et al. [89] used diamines 41, isocyanides 42 and two

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

• reacts with unsaturated systems to yield either N-chlorosulfonyl-β-lactams 3 or unsaturated N-chlorosulfonyl amides 4 (Scheme 1). β-Lactams 3 generally predominate and in many cases are the exclusive products and they serve as key substances in a variety of chemical transformations. When chlorosulfonyl

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• of an ester functional group in the structure of products makes them suitable substrates for further derivatization. Synthesis of functionalized 5-membered lactams using Ugi reaction. aIsolated yield for mixture of diastereomers. bThe ratio of diastereomers was determined by 1H NMR analysis

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• proceeded smoothly at room temperature, affording the corresponding bicyclic cyclopropane ring-fused lactones and lactams in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). After screening of various catalysts, the Ru(II)-Amm-Pheox complex having an ammonium group proved to be

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

• transformations, cyclic dienes with different ring sizes might be considered to be important starting materials for the generation of structurally diverse molecules. Among the large number of possible transformations, the ring olefinic bond of alicyclic dienes may lead to valuable β-lactams [21][22][23] or γ

• -lactams [24], shown to be highly important precursors for the access of various structures (e.g., amino acids, azido esters, hydroxylated amino esters, fluorinated amino esters, etc.) with various functional groups as well as stereochemical and skeletal diversity [21][22][23]. Results and Discussion

• Recently, we have demonstrated the high utility of various constrained cyclic dienes, such as norbornadiene as well as 1,5- and 1,3-cyclooctadienes in the context of their applicability towards the access of diverse, highly functionalized olefinated molecules [14][15][16]. The corresponding β-lactams

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• synthesis of spiro β-lactams via oxidative dearomatization reactions. In this report, the synthesis of spiro β-lactams 56 were achieved successfully by the oxidative cyclization of p-substituted phenols 55 using PIDA (15) as an electrophile and copper(II) sulfate pentahydrate as an additive in the presence

• derivatives 60 were reacted with [bis(trifluoroacetoxy)iodo]benzene (31, PIFA) in TFE at room temperature to afford functionalized lactams 61 in good yields (Scheme 20). Various electron-donating and withdrawing groups at the phenyl ring in anilides were successfully tolerated. Furthermore, Sunoj and

• 2014, Xu and Abdellaoui [93] reported a nucleophilic intramolecular cyclization of phenylacetamides 65 to spirocyclic lactams 66 via iodine(III)-mediated spirocarbocyclizations. In literature, there are limited methods available for the synthesis of spiro-β-lactam-3-carbonitrile which is widely used as

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• introduction of the iodobenzoic acid motif onto the pyrrole ring. 5-Aroyloxy-γ-lactams 4 can be isolated with yields in the 56–96% range, however, the reaction requires 2.5 equivalents of the λ5-iodane reagent, a result that supports its limited efficiency in terms of atom economy (Scheme 3) [31]. λ3-Iodane

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification

• spirocyclic oxindole γ-lactams). There have been other groups in the past, including our own research group, who have reported on post-modified Ugi-four-component synthetic strategies (Scheme 1) towards the synthesis of 2-oxindoles and spiro[indoline-3,2'-pyrrole]-2,5'(1'H)-diones and spiro[indoline-3,2

• facile to synthesize. Here within, we document that the reaction sequence for spirocyclic oxindole γ-lactams (Scheme 2) follows a three-step sequential strategy involving: a) an Ugi-4CR, b) an acid-promoted intramolecular transamidation, and c) a base-mediated cyclization giving spiro[indoline-3,2

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• -transfer catalyst; 3-substituted isoindolinones; Introduction Isoindolinones I (Figure 1), e.g., 2,3-dihydro-1H-isoindol-1-ones, also called phthalimidines are bicyclic lactams whose molecular structure is the basis of a wide range of alkaloids and biologically active compounds [1][2][3][4][5][6][7][8][9

• reactions implying the use of a chiral auxiliary resulted effectively in various optically pure compounds [10][18][19][20]. Second, enantioselective syntheses of these bicylic lactams were performed by using chiral transition metal- or organocatalysts which control the configuration of the trisubstituted

• -substituted isoindolinones 1 and 2 could be obtained in high enantioselectivities from the intermediates (2R,3S)-3–5 after removal of the chiral auxiliary (Scheme 1). (2R,3S)-bicyclic lactams 3–5 could be prepared by the asymmetric intramolecular organo-catalyzed aza-Michael reaction of (R)-benzamides 6–8

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• ortho-amidoalkylation of phenols in which a tandem Knoevenagel condensation occurs through o-QM followed by the formation of an unstable oxazine intermediate [64]. Later, the same research group published a similar reaction extended by various lactams carried out in trifluoroacetic acid in water [65

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• procedure for the synthesis of diene dithioacetals. A similar reaction using α-carbonyl substituted ketene dithioacetals for an addition to alkynes under iron catalysis was shown by Liu et al. before and was used for the synthesis of δ-lactams and lactones by 6-endo annulation [35]. Our approach reveals

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• methodology to develop the first total synthesis of chiral 13-membered lactams, such as ansamacrolactams (+)-Q-1047H-A-A and (+)-Q-1047H-R-A [35]. In this case, the intramolecular Sm(II)-mediated Reformatsky reaction was applied to chiral aldehyde 44, leading to the corresponding alcohol 45 in 84% yield as a

• under the reaction conditions to give directly the final chiral α-bromo-α-fluoro-β-lactams (3S,4R)-62a–k in moderate to high yields (53–90%) and high enantioselectivities (85–96% ee), as shown in Scheme 23. This method represented the first ligand-promoted aza-Reformatsky approach using a

• required to achieve at room temperature the corresponding chiral α,α-difluoro-β-lactams (R)-63a–h in moderate to good yields (45–76%) and high to excellent enantioselectivities (86–99% ee), as shown in Scheme 24. Using enantiomeric ligand (1S,2R)-59 under the same reaction conditions allowed the opposite

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• fused with β-lactams (Scheme 41) [56]. The competition between mono- and dichlorination remained an issue in these transformations; but fortunately, increasing the bulkiness of the ester group permitted to limit the reaction to the introduction of only one chlorine atom. It was also possible to achieve

• the isolation of similar compounds starting from differently substituted β-lactams, notably carrying a malonate moiety linked to the nitrogen [57]. More recently, CF3SO2Cl also found to be an appropriate reagent for the asymmetric introduction of a chlorine atom onto several substrates. For instance

• phenols. Mono- and dichlorination of carbon acids. Monochlorination of (N-aryl-N-hydroxy)acylacetamides. Examples of the synthesis of heterocycles fused with β-lactams through a chlorination/cyclisation process. Enantioselective chlorination of β-ketoesters and oxindoles. Enantioselective chlorination of

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

• carried out by Yavari and Nourmohammadian in good yields of 80–85% (Scheme 49) [22]. A facile route to N-acylated α,β-unsaturated γ-lactams 80 was reported by Asghari et al. The reaction of acetylenedicarboxylates with triphenylphosphine and N-acetylaminocyanoacetate gave the corresponding ylide 79. The

• -chlorotetrahydrofuran-2,4-dione. Synthesis of N-acylated α,β-unsaturated γ-lactams via resonance-stabilized phosphorus ylides derived from N-acetylaminocyanoacetate. Synthesis of resonance-stabilized phosphorus ylides derived from 6-amino-N,N'-dimethyluracil and their subsequent cyclization to bicyclic compounds

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• , diketopyrrolopyrroles (DPP) represent an unique class of organic molecules based on central, fused, and conjugated bicyclic lactams of 2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione. After its serendipitous discovery by Farnum et al. in 1974 [1] and subsequent first applications as organic, insoluble, and high-performance

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• preserved in the major cycloadduct. A non-concerted course of the reaction via the stabilized zwitterion 18b was proposed to rationalize this unexpected result. In an additional experiment performed in wet THF, mixtures of diastereoisomeric, spirocyclic seven-membered lactams 30b were isolated side by side

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• proteins against the activity of proteolytic enzymes [6][7], or are precursors of numerous active compounds such as β-lactams [8][9]. Finally, β-amino acids are present in numerous natural products [10]. These properties have generated great interest in the development of synthetic methods for the

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• or generated in situ) with α-C–H dicarboxylic acid anhydrides (known as the Castagnoli–Cushman reaction or CCR [1]) offers a direct entry into lactam frameworks 1 of various sizes (traditionally, δ- and γ- [2][3] and, more recently, ε-lactams [4][5]) containing a carboxylic acid functionality

• which may facilitate or prevent compounds’ binding to DNA or DNA-topoisomerase complex. Depending on the medicinal chemistry context, compounds 10 can be decarboxylated to deliver sterically encumbered tetracyclic lactams 14 lacking the carboxylic acid group as we showed for exemplary compound 10h. The

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• (MAO) type B inhibitors [6] often used for the treatment of neuropsychiatric disorders such as Alzheimer’s and Parkinson diseases. These alkynylamines are also important building blocks for the synthesis of N-bearing compounds such as β-lactams [7][8], pyrroles [9], pyrrolidines [10], pyrrolophanes [11

Highly reactive, liquid diacrylamides via synergistic combination of spatially arranged curing moieties

• Maximilian Maier,
• Magnus S. Schmidt,
• Markus Ringwald and
• Christoph P. Fik

Beilstein J. Org. Chem. 2017, 13, 372–383, doi:10.3762/bjoc.13.40

• the preformed five or six-membered lactams and gets even more predominant with increasing chain length of N-alkyl groups [28]. Expanding this concept in view of an optimized spatial layout, we synthesized molecules with additional “internal” (at the molecules’ center), symmetrical allyl functions

• FTIR data and literature [27][28], we propose that some of the possible intramolecular reaction products (intermolecular cyclization products are conceivable as well) start most likely from the formed acrylamide radical as depicted in Scheme 6. Upon subsequent cyclization, either 6-membered δ-lactams

• , or 5-membered γ-lactams can be formed. The emerging FTIR signal at ≈1680 cm−1 strongly indicates the formation of γ-lactams as it can be attributed to the stretching vibration of γ-lactam carbonyl groups [28]. However, the corresponding δ-lactam peak could be located below the amide peak at ≈1645 cm

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• , but also in important building blocks widely used in the organic syntheses. They are especially used in the synthesis of β-amino acids [4][5], which are precursors for many biological and pharmacological active compounds, such as β-lactams [6] and β-peptides [7]. The most straightforward approach

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• with a large substrate scope. Keywords: carbonates; DBN; DBU; lactams; p-nitrophenyl; Introduction Among various organic bases, amidines such as DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-diazabicyclo[4.3.0]non-5-ene) having an imino group attached to the α-carbon of the amine are

• products [12]. Subsequently, Ma and Dolphin isolated chlorin-e6 lactams from the reaction of methyl pheophorbide with DBU and DBN promoted by trialkyl triflates [13]. Additionally, the conjugate addition reaction of DBU to diarylpyrone [14] and Baylis–Hillman acetates [15] also gave caprolactam products. A

• . To evaluate the substrate feasibility, one phenol, an allylic alcohol and three sugar alcohols were subjected to the reaction. The 3,4-dimethylphenyl p-nitrophenyl carbonate (9a) and geranyl carbonate 10a gave the corresponding γ-lactams 9b and 10b in 62% and 46% yields, respectively. Similarly, the