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

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• pot-synthesis of 2. aBased on recovered 3. Formal synthesis of phenoxazine (1). aBased on recovered 3. Optimization of the O-arylation of route A.a Supporting Information Supporting Information File 181: Experimental details for the synthesis of starting materials and products, analytical data for

• converted to product upon longer reaction time. Compounds containing a phenoxazine moiety. Reported syntheses of phenoxazine derivatives. Retrosynthesis of phenoxazine. Synthesis of iodonium salt 5a. Synthesis of iodonium salt 7. O-Arylation via route B. a) Cyclization of diaryl ether 3. b) Attempted one

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• . Study on the presumed Togni reagent 1-mediated trifluoromethylation followed by PhIO-mediated azirination. Togni reagent/PhIO-mediated one-pot synthesis of β-trifluoromethyl 2H-azirines. Reaction conditions: 1 (1.2 mmol), 5 (1.0 mmol), CuI (0.2 mmol), PhIO (1.5 mmol) in DCE (10 mL) unless otherwise

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• the development of novel biologically active compounds based on the pyrazolopyrimidinone scaffold, we sought to develop a simple one-pot synthesis of the nitrogen-fused bicyclic system. In order to establish reaction conditions for this one-pot synthesis, we began by seeking general reaction

• conditions for the microwave-assisted generation of the intermediate 5-aminopyrazoles. Once established, this methodology could be expanded to generate a one-pot synthesis of pyrazolo[1,5-a]pyrimidinones. Typical methods for preparing 5-aminopyrazoles require conventional heating of the appropriate β

• convenient and general microwave-assisted method for the synthesis of the 5-aminopyrazoles in hand, we next focused our attention on its application to the one-pot synthesis of pyrazolo[1,5-a]pyrimidinones. The synthesis of pyrazolo[1,5-a]pyrimidinone 3a was chosen as the model reaction (Scheme 2). Initial

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• turned our attention to devise a one-pot protocol to achieve the same derivative. The one-pot synthesis of this target is particularly challenging because of the presence of the two 1,2-cis glycosidic linkages which are likely to make product isolation particularly difficult at the end of the

• orthogonal strategy for a one-pot synthesis of the targeted tetrasaccharide (Scheme 5). The disaccharide acceptor 4 was glycosylated with galactosyl trichloroacetimidate donor 2 at −15 °C using 30 mol % of TMSOTf. After full consumption of the starting materials (TLC), into the same pot the second acceptor 7

• linkages could be prepared with a yield and a selectivity which were high enough to allow the one-pot synthesis. The tetrasaccharides associated with the pneumonicoccal serogroup 6. Retrosynthetic analysis. Preparation of D-glucosyl donor 6. Reaction conditions: a) NapBr/PMBCl, NaH, DMF, rt, 12 h, 90% (6a

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• as an important scaffold. Scope of compatible aryl groups. Conditions: 1 (0.5 mmol, 1 equiv), potassium phthalimide (2.5 mmol, 5 equiv), toluene (2.5 mL), 100 °C, 24 hours. Isolated yields are reported. One-pot synthesis of anilines. Discovery and optimization of reaction conditions.a Comparison of

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China 10.3762/bjoc.14.75 Abstract A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily

• substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research. Keywords: azomethine ylides; 1,3-dipolar cycloaddition; one-pot synthesis; polysubstituted pyrroles; pyrrolo[3,4-c]pyrrole-1,3-diones

• -1,3-diones [8][9][10] via 1,3-dipolar cycloaddition without any chiral catalysts/ligands and a facile access to highly substituted pyrroles with amide groups or ester groups. Herein, we propose a straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar

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

• spirocyclic 2-oxindoles. Post-Ugi-4CR/transamidation/cyclization sequence. Base-promoted intramolecular 5-endo-dig cyclization. Reaction scope with varying combinations of substrates. Synthesis of 5-chloro-1'-phenylspiro[indoline-3,2'-pyrrolidine]-2,5'-dione (8a). Method applicability for the one-pot

• synthesis of 5-HT6 receptor antagonist 8j [53]. Optimization conditions for the intramolecular cyclization (Scheme 3, 6→7a and 7a').a Supporting Information Supporting Information File 50: 1H and 13C NMR spectroscopic data for compounds 7a–k and 8a–j, and X-ray crystal structure details for 7a

One-pot synthesis of diaryliodonium salts from arenes and aryl iodides with Oxone–sulfuric acid

• Natalia Soldatova,
• Pavel Postnikov,
• Olga Kukurina,
• Viktor V. Zhdankin,
• Akira Yoshimura,
• Thomas Wirth and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 849–855, doi:10.3762/bjoc.14.70

• sulfuric acid has been developed. The procedure allows the synthesis of a wide range of iodonium salts containing electron-donating and electron-withdrawing substituents. Particularly attractive is the possibility of the one-pot synthesis of symmetric bis-aryliodonium salts directly from arenes via an

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• 7a. ‘One-pot’ synthesis of diketopiperazine-fused triazolobenzodiazepines 7a and 7b. Synthesis of hydantoin-fused triazolobenzodiazepine 10. Reaction conditions: 1. 2-azidobenzaldehyde 1 (1.85 mmol), propargylamine (2a, 1.85 mmol), trichloroacetic acid (9, 1.85 mmol), benzyl isocyanide 4 (1.85 mmol

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

• reactions is definitely more advantageous. Ionic liquids have also attracted considerable attention due to their „green chemistry” values, including reusability, high thermal stability and non-inflammability. Hajipour et al. reported the one-pot synthesis of 1-amidoalkyl-2-naphthols catalysed by N-(4

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -bromocoumarins, the C–Br bond of 3-bromo-4-phenylcoumarin was smoothly converted into 4-phenylcoumarins bearing C–H, C–S, C–N, and C–C bonds at 3-position. We believe the present method will be useful for the preparation of various 4-arylcoumarin derivatives due to its simple one-pot synthesis. ORTEP of 3-bromo

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• 1a. Other examples of the one-pot synthesis of fluorinated phthalides 1 are given in Scheme 3. The reactions of 2-cyanobenzaldehyde (2) with organosilicon compounds (RF–SiMe3) proceeded cleanly by the use of KF (conditions A) or Et3N (conditions B). As a consequence, pentafluoroethyl