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

• observed in a one-pot synthesis from cyclopentanone, dimethyl fumarate and ammonium acetate. This multistep reaction includes 1,3-dipolar cycloaddition of dimethyl fumarate to the cyclic azomethine ylide formed in situ from cyclopentanone and ammonia. The polycyclic amine product was easily converted into

• 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

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• al. developed a programmable enantioselective one-pot synthesis of molecules with eight stereocentres greatly improving the efficiency of natural product synthesis [83]. Each of these natural products are biologically active, hence their total synthesis will allow further characterisation of their

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

• Kenta Tanaka,
• Yuta Tanaka,
• Mami Kishimoto,
• Yujiro Hoshino and
• Kiyoshi Honda

Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208

• . Keywords: Friedel–Crafts reaction; metal-free conditions; one-pot synthesis; photoredox catalyst; thioxanthylium salt; Introduction Thioxanthylium salts are one of the important structural motifs found in biologically active compounds and photochemical materials [1][2][3][4][5][6][7][8]. Owing to these

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• 58–74% yields. Then, the one-pot synthesis of α,β-di(hetero)arylated 5,6-dihydropyrrolo[3,2,1-ij]quinolines was attempted (Scheme 3). The use of a larger amount of aryl bromides (3 equiv) provided the target diarylated lilolidines 20–22 in good yields. Under these conditions, the mono-arylated

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• ), a new quinazolinone derivative in 40% yield (Scheme 6). Notably, these heterocycles are known for their use as antitumor [101], anticonvulsant [102] or epidermal growth factor receptor tyrosine kinase inhibitory agents [103], JNK inhibitors [104] or 5-HT3 antagonists [105]. Earlier, a one-pot

• synthesis of an analogous compound was accomplished by Sayahi et al. starting from isothiocyanates in the presence of CuBr [106]. As aforementioned, in some cases only isothiocyanate 8 was detected and/or isolated. Thus, in order to gain mechanistic insights on the generation of 3a, we performed a series of

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• mixture with morpholine leading to amide Z-11o. Multigram-scale one-pot synthesis of indane 12d from 2-methylbut-3-yn-2-ol. 1H, 13C, and 31P NMR monitoring of AlCl3-promoted reactions of allene 1a leading to compounds E-14 or 15 at room temperature. Plausible reaction mechanism A for the formation of

• -pot synthesis of indane 12d starting from 2-methylbut-3-yn-2-ol (Scheme 7, see procedure in Supporting Information File 1). The first stage of this procedure gave allene 1a, which was dissolved in CH2Cl2 and subjected to reaction with p-xylene under the action of AlCl3. Finally, methanolysis of the

• complex mixtures of oligomeric compounds. In the same reaction with benzene, allene 1b afforded alkene Z-11n in high yield (Scheme 5). The use of morpholine for quenching of the superacidic reaction mixture gave amide Z-11o in the reaction of 1a with benzene (Scheme 6). We also conducted a large-scale one

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• ] specifically have been published employing a cyclizing addition of an acylhydrazone to the carbonyl group as a ring-forming reaction [32][33][34][35][36][37][38][39][40], their diversity-oriented one-pot synthesis in a multicomponent approach has remained unexplored to date. In the course of our program

• additionally corroborated by X-ray structure analysis showing that the assignment of intermediate 5a was not a fully unsaturated pyrazole (Figure 4) [53]. Therefore, we set out to optimize the one-pot synthesis of 1,5-diacyl-5-hydroxypyrazolines by choosing the model reaction of phenylglyoxylic acid (1a

• –cyclization sequence of (hetero)arylglyoxylic acids, oxalyl chloride, arylacetylenes, and hydrazides does not form aromatic pyrazoles, but rather 1,5-diacyl-5-hydroxypyrazolines, i.e., the aromatizing elimination of water does not occur under these neutral conditions. This novel one-pot synthesis of 1,5

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• -lactam, albeit functionalized in the side chain. The one-pot synthesis of the β-lactam steroid was achieved via the Ugi 3-component-4-center reaction using the dehydrocholic aldehyde 1 as carbonyl component. This variation of the Ugi reaction including a β-amino acid component allows the formation of the

• (cages) by multiple multicomponent macrocyclizations based on the Ugi-4CR [73][75]. One-pot synthesis of steroidal cages by double Ugi-4CR-based macrocyclizations [76].

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• for the synthesis of molecular cages was described [50]. The approach was based on macromulticycle connectivities through bridgeheads. For the macrocyclization reaction, metal-template-driven and dilution conditions were used. These conditions allowed one-pot synthesis including aryl, heterocyclic

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• Marius Kunkel Sebastian Polarz University of Konstanz, Universitätsstrasse 10, 78467 Konstanz, Germany 10.3762/bjoc.15.87 Abstract An efficient one-pot synthesis for Janus-type fullerenol derivatives and how to characterize them is reported. This synthesis provides access to asymmetrically

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• ester cages of type 22 [64]. Mechanochemical synthesis of borasiloxane-based macrocycles. Mechanochemical synthesis of 2-dimensional aromatic polyamides. Nitschke’s tetrahedral Fe(II) cage 25. Mechanochemical one-pot synthesis of the 22-component [Fe4(AD2)6]4− 26, 11-component [Fe2(BD2)3]2− 27 and 5

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• -based MCRs. In this way, the selective formation of intermediate B, leads to the following MCR processes based in different isocyanide MCRs. This approach made possible a remarkable 8-CR process for the one-pot synthesis of compounds with up to 11 diversity points. A conceptually distinct approach for

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library

Regioselective addition of Grignard reagents to N-acylpyrazinium salts: synthesis of substituted 1,2-dihydropyrazines and Δ⁵-2-oxopiperazines

• Valentine R. St. Hilaire,
• William E. Hopkins,
• Yenteeo S. Miller,
• Srinivasa R. Dandepally and
• Alfred L. Williams

Beilstein J. Org. Chem. 2019, 15, 72–78, doi:10.3762/bjoc.15.8

• the nucleophilic addition of Grignard reagents to N-acylpyrazinium salts. A literature search showed this organometallic reagent reacting with pyrazine N-oxides towards the one-pot synthesis of N-Boc-protected N-hydroxy-substituted piperazines in good yields [6]. Methylmagnesium iodide was observed

• salts (yields refer to isolated yields). Phenyl Grignard addition to methoxy-substituted N-acylpyrazinium salts. Conversion of dihydropyrazine to Δ5-2-oxopiperazines under acidic conditions. One-pot synthesis of substituted Δ5-2-oxopiperazines. Supporting Information Supporting Information File 14

DABCO- and DBU-promoted one-pot reaction of N-sulfonyl ketimines with Morita–Baylis–Hillman carbonates: a sequential approach to (2-hydroxyaryl)nicotinate derivatives

• Soumitra Guin,
• Raman Gupta,
• Debashis Majee and
• Sampak Samanta

Beilstein J. Org. Chem. 2018, 14, 2771–2778, doi:10.3762/bjoc.14.254

• Soumitra Guin Raman Gupta Debashis Majee Sampak Samanta Discipline of Chemistry, Indian Institute of Technology Indore, Simrol, Indore, 453552, Madhya Pradesh, India 10.3762/bjoc.14.254 Abstract An intriguing DABCO-catalyzed and DBU-promoted one-pot synthesis of an important class of (2

• mol %) in toluene at 60 °C for 6–8 h, followed by the addition of DBU (0.24 mmol, 1.2 equiv) at the same temperature in an open atmosphere. One-pot synthesis of (2-hydroxyaryl)nicotinonitriles 5ak–5am. Optimization reaction conditions. Supporting Information Supporting Information File 380: Synthetic

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• , 22.2, 14 ppm. The analytical data matched those reported in the literature [39]. One-pot synthesis of 2-hydroxy-6-tridecylbenzoic acid (3) An oven-dried 20 mL vial was charged with Ru-1 (3 mg, 5.00 μmol), 2 (131 mg, 0.50 mmol) and closed with a crimp cap. The vial was evacuated and backfilled three

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• was carried out for several salicylaldehydes and gave a clear improvement in the yield of the corresponding triazolochromenes and consequently showed to be a viable alternative for solid salicylaldehydes. Keywords: ball milling; multicomponent reaction; 3-nitro-2H-chromene; one-pot synthesis; 1,2,3

• since the 3-nitro-2H-chromenes and their starting materials show similar retention factors. Since the triazolochromenes 5 are showing much lower retention factors, the one-pot synthesis would display a great improvement in the labor intensiveness both for the purification steps and reaction set-up. The

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• discovered the one-pot synthesis of coumarin derivatives via hydrocarboxylation/alkene isomerization/cyclization reactions (Scheme 22) [49]. A key of the sequential reactions is a use of aromatic alkynes bearing a momo-protected hydroxy group at the ortho position on the aromatic ring (23). The corresponding

• -light-driven hydrocarboxylation of alkynes. Visible-light-driven synthesis of γ-hydroxybutenolides from ortho-ester-substituted aryl alkynes. One-pot synthesis of coumarines and 2-quinolones via hydrocarboxylation/alkyne isomerization/cyclization. Proposed reaction mechanism for the Co-catalyzed

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• Edwin Alfonzo Jesse W. L. Mendoza Aaron B. Beeler Department of Chemistry, Boston University, Boston, Massachusetts 02215, United States 10.3762/bjoc.14.205 Abstract A one-pot synthesis of epoxides from commercially available benzyl alcohols and aldehydes is described. The reaction proceeds

• expedient access to epoxides from commercially available materials in a step and time economical fashion. In particular, we have demonstrated its applicability to the synthesis of epoxides that were generally unattainable using the standard mCPBA epoxidation. Scope of the one-pot synthesis of epoxides from

• benzyl alcohols and aldehydes. Scope of the reaction with electron-rich alcohols and aldehydes. One-pot synthesis of epoxides from benzyl alcohols and aldehydes. mCPBA epoxidation of electron-rich stilbene derivatives. Supporting Information Supporting Information File 398: Experimental procedures and

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• getting considered as ‘flow version’ of conventional ‘one-pot synthesis’, multistep flow synthesis has become the next generation tool for creating libraries of new molecules. Here we give a more ‘engineering’ look at the possibility of developing a ‘unified multistep flow synthesis platform’. A detailed

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• zinc/aluminium chloride. Movassagh et al. reported another simple, general and highly regioselective one pot synthesis of β-hydroxy sulfides in good yields from the reaction of styrenes and disulfides using Zn/AlCl3 as a catalyst in aqueous CH3CN at 80 °C, in the presence of oxygen as oxidant (Scheme

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• starting materials, was detected. aNo reaction in the presence of comparable amounts of NH4Br or SiO2. b1e is almost insoluble in CPME. c1:1 mixture of diastereoisomers. Deprotection of THP ether 3i. One-pot synthesis of 3-[4-(tetrahydro-2H-pyran-2-yl)oxymethylphenyl]-3-pentanol (4fa). One-pot synthesis of

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• published a direct one-pot synthesis of exclusively β-configured nucleosides from unprotected or 5-O-monoprotected D-ribose using optimized Mitsunobu conditions with various purine- and pyrimidine-based heterocycles. Here, DBU was applied first, followed by DIAD and P(n-Bu)3 [106]. Two years later Seio and

Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• the β-fragmentation of the C1–C2 bond. As a result, a C2 radical is generated and is further oxidized to a carbocation that is reacted with nucleophilic agents to give the desired products. Boto et al. applied the reaction to the one-pot synthesis of acyclic nucleosides that belong to an important