Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• modifications The one-pot three-component reaction between aldehydes 19 (or ketones), amines 20 and dialkyl phosphonates 21 to afford α-aminophosphonates 22 is traditionally known as the Kabachnik–Fields reaction. This reaction was first reported in 1952 by Kabachnik, Medved and Fields (Scheme 6) [29][30]. Due

• -aminophosphonates. Unfortunately there are only a few examples of Kabachnik–Fields reactions of heterocycloalkanones in the literature. The tetra(tert-butyl)phthalocyanine–AlCl complex catalyzed three component reaction of N-Boc-piperidin-4-one (23) with (EtO)2P(O)H (24) and benzylamine (25) afforded the cyclic α

• and the structure of the dialkyl phosphite and isatin (Scheme 9) [35]. In this way a one-pot three-component reaction between 1-tosylpiperidine-4-one (34), aromatic amines 35 and diethyl phosphonate in the presence of magnesium perchlorate as a catalyst, under neat conditions at 80 °C afforded α

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• conditions to prepare N-(pyren-1-ylidene)-tert-butylamine (1j) and dimethyl N-(tert-butyl)amino(pyren-1-yl)methylphosphonate (3Aj) via the aza-Pudovik reaction, the Kabachnik–Fields reaction was used as an alternative method [23]. The three-component reaction without any catalyst was carried out first in

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• led to undesired side reactions, e.g., deacylation or oligomerization processes. The development of the discussed pyridine syntheses by cyclocondensation reactions of β-ketoenamides was inspired by a serendipitously discovered three-component reaction of lithiated alkoxyallenes, nitriles and

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• corresponding azide for the next CuAAC reaction to give the desired bistriazoles. In 2007, Wang and co-workers demonstrated that the one-pot three-component reaction of ortho- and meta-bis(chloromethyl)benzene (62), sodium azide, and terminal alkynes, catalyzed by CuX in water could provide the corresponding

• 1,4-disubstitued bistriazoles 63 in excellent yield [64] (Scheme 21). They found that the bistriazole could be formed during the Huisgen reaction, in which the reaction was efficiently promoted by the catalytic amount of the Cu(I) salts. For example, the three-component reaction could reach completion

• bistriazoles. The pyrene-appended thiacalix[4]arene-based bistriazole. The synthesis of triazole-based tetradentate ligands. The synthesis of phenanthroline-2,9-bistriazoles. The three-component reaction for the synthesis of bistriazoles. The one-pot synthesis of bistriazoles. The synthesis of polymer-bearing

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• uncharted. In this paper, a three-component reaction between α,β-unsaturated aldehydes, alcohols and the Bestmann ylide is described. The scope of this esterification–Wittig reaction sequence in the synthesis of α,β,γ,δ-unsaturated esters is studied, and the method is applied in an approach towards the

• Discussion Evaluation of the three-component reaction for the synthesis of α,β,γ,δ-unsaturated esters The study of the reactions between Bestmann ylide, alcohols and α,β-unsaturated aldehydes began with the investigation of the coupling between linchpin 1 [46], E-hex-2-en-1-ol (9a) and E-cinnamaldehyde (10a

• -component reaction between (triphenylphosphoranylidene)ketene (Bestmann ylide, 1), an alcohol and an unsaturated aldehyde delivers α,β,γ,δ-unsaturated esters. This methodology enabled the facile synthesis of E,Z-dienoate products 5b and 5c, which represent two-thirds of the dactylolide/zampanolide

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• -component reaction of ester 1f, cyanoacetic ester 12 and 5-AT in the presence of triethylamine to confirm the proposed mechanism. The product 11 was obtained in excellent yield. Moreover, we managed to isolate diethyl 2,4-dicyanopent-2-enedioate (14, Scheme 5), which was previously obtained as a sodium salt

• [М]+) (Scheme 5). It can be assumed that ethyl cyanoacetate (12), formed as a result of ethoxymethylidene group migration to 5-AT, reacts with ester 1f to give intermediate diester 14 (Scheme 5). The latter is cyclised with 5-AT into pyridine 11 via intermediates H and I. We carried out the three

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• approach to CF3-pyrazoles by a three-component reaction between electron-deficient alkynes, sodium nitrite and trifluoroethylamine hydrochloride was developed [46]. This method worked for both the mono- and disubstituted alkynes. Because of similar electronic properties of CF3 and C2F5 groups [1], it was

• AS-136A [55]) (Scheme 3). Conclusion In summary, a novel approach to C2F5-substituted pyrazoles has been elaborated by a three-component reaction between C2F5CH2NH2·HCl, NaNO2 and electron-deficient alkynes. This method is highly practical: it does not require a) the pre-isolation of toxic diazo

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• at room temperature for 4 h without catalyst always led to the selective formation of the corresponding chroman-3-carboxamides 4a–h (Table 3, entries 1, 4, 7, 10, 13, 16, 19, 22). However, to our surprise, the ytterbium triflate-catalyzed three-component reaction of 5-amino-3-methylisoxazole (1

• . Some Biginelli-type three-component condensations with salicylaldehyde. Three-component heterocyclization of 5-amino-3-methylisoxazole (1), salicylaldehyde (2) and N-(2-methoxyphenyl)-3-oxobutanamide (3a). Possible pathways for the three-component reaction of 5-amino-3-methylisoxazole (1

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• from benzimidazoles unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature, led directly to pyrrolo[1,2-a]quinoxalin-4-ones in fair yield by an one-pot three-component reaction

• ][9][10][11][12][13]. The development of more efficient synthetic methods towards these compounds is an active research area [14][15][16]. Recently, we reported on the formation of pyrrolo[1,2-a]benzimidazoles along with pyrrolo[1,2-a]quinoxalines in the one-pot three-component reaction of 1

• starting from benzimidazole derivatives unsubstituted at the five membered ring, alkyl bromoacetates and non-symmetrical electron-deficient alkynes in the molar ratio of 1:2:1, in 1,2-epoxybutane at reflux temperature. Results and Discussion The one-pot three-component reaction of 1-substituted

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -aminoazoles, including thiazole [13][14] and 1,3,4-thiadiazole [15][16] derivatives, or 2-aminoazine-based heterocycles, such as pyridines [17][18][19], pyrimidines [20][21][22][23][24] and pyrazines [25][26][27], have recently been utilized as Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• amidines. However, it should be emphasized that our protocol with low catalyst loading (1 mol %) makes it a cleaner and lower environmental impact methodology to access α-amino amidines. Then, we tried the three-component reaction using heteroaromatic amines such as 2-aminopyridine, 3-aminopyridine and 4

• ]. Recently, catalytic iodine (10 mol %) was found to give good yields of imidazolopyridine in a three-component reaction of 2-amino-5-chloropyridine, isocyanide, and aldehydes under reflux conditions [28]. However, we found that the similar reaction using 2-amonopyridine could be performed at ambient

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• the C-4-substituted 1,4-DHP nucleobase can be efficiently obtained from the three-component reaction between the sugar aldehyde 86, ethyl acetoacetate, and ethyl 3-aminocrotonate [108][109]. The course of the reaction in the presence of various additives was examined in detail. The best results were

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• first, followed by the formation of triazole by CuAAC reaction to give the desired product 4a. Conclusion We developed a novel microwave-assisted, Cu(I)-catalyzed, three-component reaction for the synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles in good to

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• , Italy Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘Giulio Natta’, Politecnico di Milano, p.zza Leonardo da Vinci 32, 20133 Milano, Italy 10.3762/bjoc.10.141 Abstract An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid

• examples with satisfactory selectivity were achieved to date [32][33][34][35][36]. Results and Discussion Relying on our previous experience, we selected chiral ketimine 1 as a suitable substrate and started to investigate the Ugi three-component reaction (3CR) with tert-butyl isocyanide (2a) and

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• works have discovered that some analogues of San A inhibit Hsp 90, a key protein that enables many proteins involved in tumor progression [35][36][37][38][39]. The Passerini three-component reaction (P-3CR) allows an easy access to depsipeptides using a convergent approach. It has become a powerful tool

Synthesis of fluorescent (benzyloxycarbonylamino)(aryl)methylphosphonates

• Michał Górny vel Górniak,
• Anna Czernicka,
• Piotr Młynarz,
• Waldemar Balcerzak and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 741–745, doi:10.3762/bjoc.10.68

• tissues. Thus, their libraries may serve for the construction of diagnostic tools. A similar approach has been recently patented as a mean to differentiate lipases and esterases [15]. The objective of this paper is to evaluate the utility of a popular three component reaction of triaryl phosphites with

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• efforts have established H-phosphinates R(H)P(O)(OR′) or appropriate P(III) acids R(H)P(O)(OH) as appropriate starting materials for the preparation of aminophosphinic acids. The most typical route involves the three-component reaction of an aldehyde, an amine and a P–H substrate in a one-pot Mannich type

• . This resulted in the preparation of the analogues of glycine 14a and phenylglycine 14b (Scheme 3). The three-component reaction with formaldehyde gave the best results and N-protected aminophosphinic acid 13a was isolated in a moderate yield, alongside phosphonic acid 10. The analogous reaction with

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• . the incorporation of bifunctional substrates or by activation of functionalized substrates in the initial MCR [19]. The Passerini reaction The first isocyanide-based MCR was described by Mario Passerini in 1921 and named after him. The Passerini reaction is a three-component reaction (3-CR) and

• -formation of the imine or the use of bifunctional inputs (e.g. amino acids) can reduce this Ugi-4CR to an Ugi-3CR. In particular, the Ugi reaction with bifunctional inputs is called an Ugi-four-center-three-component reaction (U-4C-3CR) and has been extensively applied in peptidomimetic synthesis [21][22

• , the group of Fülöp reported an efficient synthesis of bicyclic β-lactams from monocyclic β-amino acids via an Ugi four-center three-component reaction (U-4C-3R) [39]. Herein, the monocyclic β-amino acid acts as bifunctional moiety containing both an amino and carboxylic acid group. A variety of cyclic

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• ], phenylacetylene [73][74], and methyl acrylate [75]. Starting from these results, a MC approach to 1-(isoquinolin-1-yl)guanidines 55 was efficiently developed by a silver triflate-catalyzed three-component reaction of 2-alkynylbenzaldehydes 25, tosylhydrazide (41) and carbodiimides 54 (Scheme 29) [76]. The

• , aldehydes and alkenes in a three-component reaction based on the cascade imine formation, azomethine ylide generation and [3 + 2] cycloaddition reaction for the synthesis of pyrrolidines. However, the adopted method to induce chirality in the final products is rather dissimilar. Thus, in 2006 Garner’s group

• , which by loss of the tosyl group and base-catalyzed aromatization yields the H-pyrazolo[5,1-a]isoquinoline 48. Finally, a new series of fully aromatic pyrazolo[5,1-a]isoquinolines 53, bearing an amino group in position 2 can be synthesized under silver triflate catalysis by the usual three-component

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• ), (E)-3-(dimethylamino)-1-(3-nitrophenyl)prop-2-en-1-one (1 mmol) and 4-methoxyaniline (1 mmol). This three-component reaction was initially examined in solvents such as acetonitrile, dioxane, dimethyl sulfoxide, toluene and ethanol under heating. However, the only isolable product was compound 4d

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• related compounds by a new manganese-mediated, cobalt-catalyzed three-component reaction between sulfonamides, carbonyl compounds and organic bromides is described. This organometallic Mannich-like process allows the formation of the coupling products within minutes at room temperature. A possible

• and versatility of multicomponent procedures, we describe herein a new manganese-mediated, cobalt-catalyzed three-component reaction, which circumvents the above-mentioned limitations by allowing the synthesis of an extended range of (diarylmethyl)sulfonamides (and related compounds) within minutes at

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• extension of the substrate scope of the Flögel-three-component reaction of lithiated alkoxyallenes, nitriles and carboxylic acids is presented. The use of dicarboxylic acids allowed the preparation of symmetrical bis(β-ketoenamides) from simple starting materials in moderate yields. Cyclocondensations of

• – discovered and mechanistically elucidated by Oliver Flögel – features a three-component reaction that employs alkoxyallenes, nitriles and carboxylic acids: upon treatment with n-butyllithium the allene is lithiated in α-position to the alkoxy moiety; the addition of a nitrile as electrophile to this highly

• heteroaromatic systems containing up to six conjugated aryl and hetaryl groups. Complementary examples employing aromatic dinitriles in this Flögel-three-component reaction have previously been presented [39]. Results and Discussion As typical model substrates we chose to employ isophthalic acid (11) and

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• our knowledge, the reversal of the regioselectivity in the 1,3-dipolar cycloaddition of azomethine ylide induced by the additive is reported for the first time. Results and Discussion Initially, a three-component reaction of isatin (1a), benzylamine (2) and benzylideneacetone (3a) was conducted in