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

• Hong Gao Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.330 Abstract The four-component reaction of 2-aminobenzothiazole, aromatic aldehydes, acetylenedicarboxylate and piperidine or pyrrolidine in ethanol afforded the

• functionalized 2-pyrrolidinones containing both benzothiazolyl and piperidinyl (or pyrrolidinyl) units in good yields. On the other hand, the similar four-component reactions resulted in the functionalized morpholinium or piperidinium 2-pyrrolidinon-3-olates in the presence of p-toluenesulfonic acid. Keywords

• synthesis of a versatile heterocyclic system, herein we wish to report the interesting results of the four-component reaction of secondary cyclic amines, acetylenedicarboxylate, 2-aminobenzothiazole and aromatic aldehydes and the efficient synthesis of the complex 2-pyrrolidinones containing both

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• , Department of Chemistry, University of Delhi, Delhi-110 007, India Chemistry Building-4.20b, School of Chemistry, The University of Manchester, Manchester M13 9PL, UK 10.3762/bjoc.9.246 Abstract An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces

• ][39][40][41][42][43]. We have recently reported a post-Ugi gold-catalyzed intramolecular domino cyclization sequence which produces spiroindolines (Scheme 1) [44]. The first step in this sequence is an Ugi four-component reaction (Ugi-4CR) [4][5] with 2-alkynoic acid as an alkyne source. The second

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• spectroscopic properties. Microwave flow reactor for the Bohlmann–Rahtz synthesis of pyridine 2b. Mesoscale production of heterocycles in a continuous flow microwave reactor [44][45][46]. The original Bohlmann–Rahtz synthesis of pyridines [49]. Bohlmann–Rahtz synthesis of pyridine 2b. Four-component synthesis

• of Hantzsch DHP 15a,b. Three- or four-component synthesis of Hantzsch DHP 15c,d. Batch and flow experiments for Bohlmann–Rahtz synthesis of pyridine 2b. Batch and flow experiments for 4-component Hantzsch DHP 15 synthesis. Synthesis of Hantzsch DHP 15c,d from propargyl aldehydes 14c,d in batch and

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• Li-Juan Zhang Qun Wu Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.9.97 Abstract In the presence of triethylamine as catalyst, the one-pot four-component reactions of arylamines, methyl propiolate, isatin and

• arylamines and other primary amines. Keywords: 1,4-dihydropyridine; electron-deficient alkyne; four-component reaction; isatin; one-pot reaction; spiro compound; Introduction β-Enaminones and β-enamino esters represent important synthetic building blocks for the development of versatile carbon–carbon bond

• functionalized spiro[indole-3,4’-pyridines] via the four-component reaction prompted us to study the reaction scope further [25]. Another widely used electron-deficient alkyne reagent, methyl propiolate, was utilized to replace dimethyl acetylenedicarboxylate as one component. The addition reaction of aniline to

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• allylmagnesiation of alkynyl sulfone. Copper-catalyzed four-component reaction of alkynyl sulfoxide with alkylzinc reagent, diiodomethane, and benzaldehyde. Rhodium-catalyzed reaction of aryl alkynyl ketones with arylzinc reagents. Allylmagnesiation of propargyl alcohol, which provides the anti-addition product

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

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

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• three-component reaction of arylamine, isatin and cyclopentane-1,3-dione. Results and Discussion Recently we found that the four-component reactions of arylamine, acetylenedicarboxylate, isatin and dimedone in acetic acid resulted in the novel functionalized tetrahydrospiro[indoline-3,2’-quinoline

• ] derivatives in moderate yields (Scheme 1a) [15]. In order to explore the generality of this four-component reaction, the reactivity of the other cyclic 1,3-diketones was also investigated. In an exploratory experiment, the four-component reaction of p-methoxyaniline, dimethyl acetylenedicarboxylate, 1-benzyl

• of spiro[dihydropyridine-oxindole] 1b. The two kinds of spiro compounds from reactions of isatins with arylamines and cyclic 1,3-diketones. Molecular structure of spiro[dihydropyridine-oxindole] 2f. Molecular structure of compound 3d. The four-component reactions containing dimedone (a) and

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• strategies and affords the optically active natural product in 20% overall yield over six steps. A more economical approach with only four steps leads to the similarly active racemate by utilizing a Ugi four-component reaction (Ugi-4CR) as the key transformation. A small library of viridic acid analogues is

• a bidirectional sequence from the least- to the most-reactive amine (NMe-Val < H-Ant-OBn < H-Gly) to yield the protected tetrapeptide 2 (Scheme 1a). Alternatively, a multicomponent (MCR) approach based on a Ugi four-component reaction (Ugi-4CR) of dipeptide 3, isobutyraldehyde, methylamine and

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• piperidine-based manifold 15 bearing an amino group in order to produce variations of branched precursors leading to distinct scaffolds (Scheme 5). The manifold 15 was readily prepared through Curtius rearrangement of 6 and subsequent removal of the resulting carbamate group. Ugi four-component condensation

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• /bjoc.8.64 Abstract A versatile nitro-Mannich/lactamisation cascade for the direct stereoselective synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles has been developed. A highly enantioenriched substituted 5-nitropiperidin-2-one was synthesised in a four component one-pot

• synthesised in a four-component one-pot cascade combining an enantioselective Michael addition with the diastereoselective nitro-Mannich/lactamisation cascade. Protodenitration and chemoselective reductive manipulation of the heterocycles could be used to install contiguous and fully substituted stereocentres

• diastereomer 2m isolated in 5% yield. Possible explanations for the observed high stereoselectivities in the nitro-Mannich/lactamisation cascade. Thermodynamically-driven epimerisation of 5-nitropiperidin-2-ones 2m and 2m’. One-pot three/four-component enantioselective Michael addition/nitro-Mannich

Impact of the level of complexity in self-sorting: Fabrication of a supramolecular scalene triangle

• Kingsuk Mahata and
• Michael Schmittel

Beilstein J. Org. Chem. 2011, 7, 1555–1561, doi:10.3762/bjoc.7.183

• constitutionally clean when self-sorting occurred along the algorithm with the higher level of complexity (Scheme 1). Due to the beauty of self-sorting, the five-component assembly (five different starting materials, mixed metal scenario) was flawless as compared to the four-component assembly (four different

Synthesis of (−)-julocrotine and a diversity oriented Ugi-approach to analogues and probes

• Ricardo A. W. Neves Filho,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2011, 7, 1504–1507, doi:10.3762/bjoc.7.175

• heterocyclic precursor as an amino input in Ugi four-component reactions (Ugi-4CR) [1]. Keywords: diversity oriented synthesis; julocrotine; leishmania; Mitsunobu reaction; Ugi reaction; Introduction Julocrotine (1) is a natural glutarimide alkaloid isolated from several plants of the genus Croton [2][3][4

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• another allenic unit. After a new transmetalation step with the boronic acid, the active catalytic species can be released and entered into a new catalytic cycle (Scheme 13). Imine as a nucleophilic partner A tandem four-component reaction allowing access to 1,2-dihydroisoquinolin-1-ylphosphonates 26 was

• different approach to α,β-alkynyl ketone derivatives as pyrazole precursors. They established a four-component domino process combining various organic halides, terminal alkynes, hydrazines, and carbon monoxide at room temperature. In this case, all components are mixed at the very beginning of the process

• the intermediacy of α,β-alkynyl ketones in the four-component process could not be confirmed (TLC). In addition, their reaction with hydrazines was shown to be ineffective under the present solvent system in the presence or absence of palladium catalyst. This may suggest that if α,β-alkynyl ketones

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• Pyrazolidinones were prepared in a two-step sequence starting from α-hydrazonocarboxylic acids. After a four-component Ugi coupling, the resulting hydrazone was engaged in a copper triggered [3 + 2] cycloaddition/aerobic oxidation cascade. Keywords: aerobic oxidation; copper(II); [3 + 2] cycloaddition; hydrazone

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• Charlotte F. Gers Julia Rosellen Eugen Merkul Thomas J. J. Muller Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.7.136 Abstract A novel one-pot four-component synthesis of pyrimidyl

• one-pot four-component syntheses toward pyrimidyl- and pyrazolylazulenes. Results and Discussion Recently, we reported a three-component synthesis leading to the formation of ynones by a conceptually novel glyoxylation–decarbonylative Sonogashira coupling sequence (Scheme 2) [47]. The Lewis acid free

• relatively low yields were achieved. With this versatile three-component synthesis of azulenylynones in hand, the stage was set to expand the sequence to a four-component access to pyrimidyl- and pyrazolyl-substituted azulenes. Hence, the conditions for the terminating Michael addition–cyclocondensation step

Novel synthesis of pseudopeptides bearing a difluoromethyl group by Ugi reaction and desulfanylation

• Jingjing Wu,
• Hui Li and
• Song Cao

Beilstein J. Org. Chem. 2011, 7, 1070–1074, doi:10.3762/bjoc.7.123

• triglyceride transfer protein (MTP) and useful for the treatment of obesity and atherosclerosis (Figure 1) [20]. Among the protocols for the preparation of pseudopeptide derivatives, the Ugi four-component reaction offers significant advantages over conventional linear-step synthesis [21]. Various fluorinated

• building blocks have been used in the Ugi four-component reaction to construct a fluorinated compound library [22][23][24][25]. Our group has always been interested in developing efficient methods for the preparation of difluoromethyl-containing compounds through multicomponent reactions [26][27][28][29

Templated versus non-templated synthesis of benzo-21-crown-7 and the influence of substituents on its complexing properties

• Wei Jiang and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2010, 6, No. 14, doi:10.3762/bjoc.6.14

• construction of a four-component self-sorting system based on the fact that C7 cannot pass over a phenyl stopper group at the end of a dialkylammonium axle, while DB24C8 can [26]. This system was further extended to construct more complex multiply interlocked structures by using the strategy of integrative

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

Synthesis of dihydrophenanthridines by a sequence of Ugi-4CR and palladium- catalyzed intramolecular C-H functionalization

• Florence Bonnaterre,
• Michèle Bois-Choussy and
• Jieping Zhu

Beilstein J. Org. Chem. 2008, 4, No. 10, doi:10.3762/bjoc.4.10

• . Introduction Multicomponent reactions (MCRs) offer a unique way to generate efficiently libraries of complex molecules with high degree of diversity [1][2]. Among them, the Ugi four component reaction (Ugi-4CR) is without doubt one of the most powerful transformations that has been extensively investigated for

• Scheme 1. The Ugi four-component reaction between an o-iodobenzaldehyde 2, an aniline 3, an isocyanide 4 and a carboxylic acid 5 should afford an α-acetamido-α-phenylacetamide 6, which upon palladium-catalyzed C-H activation process should provide dihydrophenanthridine 1 [15][16][17][18][19][20][21

• temperature afforded the four-component adduct 6a (R1 = R2 = H, R3 = tert-butyl, R4 = n-propyl) in 84% yield. Cyclization of 6a was examined under a variety of conditions and the results are summarized in Table 1. Treatment of 6a under conditions we developed previously for the synthesis of tetracyclic