Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• the HOMO/LUMO energy gap is small and that the reaction between thiosemicarbazone and benzyl is kinetically favored, probably controlled by the frontier orbital component. Furthermore, calculations of HOMO and LUMO frontier orbital coefficients were used to prove the regiochemistry in cycloaddition

• reactions [15][16]. The main objective of this work has been the synthesis of a series of polyazaheterocycles through cyclocondensation reactions between a β-enaminodiketone and several 1,3-dinucleophiles. Due to the versatility of the precursors, a wide range of compounds was expected. Hence, DFT-B3LYP

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• , antitubercular, anticonvulsant and cardiovascular activities [11][12][13][14][15][16]. As part of our interest in the exploration of 1,3-dipolar cycloaddition reactions [17] for the synthesis of polycyclic molecules, N-alkylated vinylindoles are applied as dipolarophiles in view of the challenges that still pose

• . Conclusion In conclusion, the present work explores the use of 1,3-dipolar cycloaddition reactions for the regio- and stereospecific synthesis of functionalized spiropyrrolidines through a one-pot multicomponent reaction. This new route involving a vinyl framework gives rise to a wide array of novel

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• [2 + 3] dipolar cycloaddition reactions, or click reactions [10][11][12]. Indeed, our group has reported on PRXs bearing azide groups at the threading CDs for the introduction of ligands and fluorescent molecules in biomaterials applications [13][14]. PRXs bearing reactive azide or alkynyl groups at

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• -dipolar cycloaddition process have been rationalized through a mechanistic study on the basis of our expertise in the study of cycloaddition reactions and heterocyclic compounds [37][38][39][40][41][42]. Calculations were performed using the Gaussian09 program package, [43] through optimizations with the

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• cross-coupling reactions, cycloaddition reactions, radical reactions and reductive addition reactions. A terminal alkyne can also react as nucleophile or serve as synthon for pyrrole rings [24][25]. Thus we here fuse the rich alkyne chemistry to the EDOT backbone, resulting in a novel EDOT derivative

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

• Florin Albota,
• Mino R. Caira,
• Constantin Draghici,
• Florea Dumitrascu and
• Denisa E. Dumitrescu

Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245

• other metals and represent a versatile tool for obtaining hybrid heterocycles with properties that are useful for the development of new advanced materials and for medicinal purposes [1][2][3][4]. Recently, we obtained, by 1,3-dipolar cycloaddition reactions of sydnone-ylides as bis(1,3-dipoles) with

• interesting chemical reactions of sydnones are their electrophilic substitution at C-4 and their participation in 1,3-dipolar cycloaddition reactions with olefinic and acetylenic dipolarophiles to form pyrazoles and functional transformation at C-4 [20][21][22][23][24][25][26]. Herein we present the synthesis

• than 30 different types of biological activity and they are highly fluorescent compounds the synthesis of new compounds with an indolizine framework is of great interest. The Chichibabin method and 1,3-dipolar cycloaddition reactions of pyridinium N-ylides with acetylenic dipolarophiles are two of the

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• -azolyl-1,3-dicarbonyl compounds with hydroxylamine and cyanomethylazoles with hydroxamoyl chlorides are used for the synthesis of a few representatives of 4-(azol-5-yl)isoxazoles [1][4][12][13][14][15][16]. Cycloaddition reactions of azolylacetylenes with nitrile oxides are an alternative method for the

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• cycloaddition one of the most valuable means of combinatorial chemistry. Such multicomponent reactions are characterized by productivity, operational simplicity, and efficiency [9][10][11][12][13]. A highly interesting class of heterocycles which is accessible through 1,3-dipolar cycloaddition reactions are

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• using one-pot intermolecular or intramolecular [3 + 2] azomethine ylide cycloadditions [22][23][24][25][26][27] as the initial step followed by cyclization or cycloaddition reactions to form polycyclic scaffolds with skeleton, substitution, and stereochemistry diversities. Introduced in this paper is a

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ) or versipelostatin A (153) result from formal [4 + 2] cycloaddition reactions between exo-methylene groups and conjugated dienes. The required exo-methylene groups are installed by formal dehydration of 5-hydroxymethyltetronates. Leadlay et al. have confirmed that the respective reaction in

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• amide catalysts in other reactions are ongoing. Experimental A general experimental procedure for conducting catalytic asymmetric [3 + 2] cycloaddition reactions with 0.01 mol % catalyst loading is described. Under an Ar atmosphere, a solution of the preformed chiral CuHMDS catalyst [prepared from KHMDS

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• ; Introduction The power of “donor–acceptor” (D–A) cyclopropanes as versatile 1,3-dipolar components is fuelled by its capacity of serving a complementary approach to a wide array of 5-membered ring structures, which are difficult or impossible to access by classic [3 + 2] cycloaddition reactions [1][2][3][4][5

• due to the minimization of the A[1][3] interaction. Therefore, it is observed 3a’ produced from corresponding 8a’ as the major diastereomer whereas 3a” as minor one. Conclusion We have developed a cooperative catalytic strategy for highly regio- and enantioselective [3 + 2] cycloaddition reactions of

• cycloaddition reactions involving enals and other D–A systems. The endeavor is being pursued in our laboratories. Experimental General procedure for the [3 + 2] annulation A mixture of 1a (0.2 mmol, 36.8 mg), 2a (0.2 mmol, 26.4 mg), Pd2(dba)3 (0.01 mmol, 9.2 mg), dppe (0.025 mmol, 10 mg) and I (0.06 mmol, 18.5

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

• heterocyclic phosphonates: (a) the direct electrophilic or nucleophilic phosphorylation of the heterocyclic systems and (b) the ring closure of phosphoryl-functionalized substrates through cyclization or cycloaddition reactions [14][15][16][17][18][19]. Multicomponent reactions (MCRs) constitute one of the

• . Some of these post-MCR transformations are: intramolecular cycloaddition reactions, Knoevenagel condensations, metathesis reactions, aza-Wittig reactions, Mitsunobu reactions, etc. [21]. Up to now, two review articles have been reported on azaheterocyclic phosphonates [22][23], but no overview article

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• functionality on the substrate in question. For example, Hayashi has shown that a rhodium/phosphoramidite catalysis is particularly effective for asymmetric [5 + 2] cycloaddition reactions (Scheme 2b). The (S,R,R)-diastereomer of the Feringa-style phosphoramidite ligand proved to be crucial to both the yield

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• their characteristics of convertion to vinyliminium species or the delocalized carbocation intermediates in the presence of Lewis or Brønsted acids (LA or BA). In addition to the aforementioned studies on the nucleophilic substitutions, another research focus is the 3-indolylmethanol-based cycloaddition

• reactions for constructing structurally novel and complex polycyclic scaffolds (Scheme 53). A pioneering work has been done on the 3-indolylmethanol-involved cycloaddtion reactions by the Shi group. In 2014, Shi et al. developed a CPA-catalyzed asymmetric [3 + 3] cycloaddition of 3-indolylmethanols with

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• . Remarkably, in no single case, the ‘head-to-head dimerization’ of aryl/hetaryl and dihetaryl substituted thiocarbonyl ylides was observed. Keywords: [3 + 2]-cycloadditions; diazoalkanes; diradicals; 1,3-dithiolanes; reaction mechanisms; thioketones; Introduction Cycloaddition reactions belong to the most

• -thiadiazolines of type 2 can be obtained at low temperature and subsequently used as precursors of new thiocarbonyl ylides. The latter may be potentially useful for the [3 + 2]-cycloaddition reactions with diverse dipolarophiles leading to five-membered S-heterocycles, such as di- and tetrahydrothiophenes, 1,3

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• their theoretical interest [5][6] and synthetic applications [7][8][9][10][11][12][13][14][15]. In this latter sense, fulvenes can be involved in multiple modes of cyclization processes such as [4 + 2] [7][8], [6 + 2] [9][10][11], and [6 + 3] [12][13][14][15] cycloaddition reactions resulting in the

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

• azides. (3) The third method involves the utilization of the substrate bearing two alkyne moieties with different reactivity in the successive Huisgen cycloaddition reactions: Huigsen reaction of the activated alkyne with the first azide and the CuAAC reaction of the nonactivated alkyne with another

• (OAc)2) could catalyze the Huisgen alkyne-azide cycloaddition reactions without the addition of the reducing agents and could be produced in high yield when the substrate contains the chelating azide group [67]. Then they synthesized the bifunctional compounds with chelating azide groups and

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• -3-carboxylic acid derivatives 3, constrained analogues of tryptophan, could be synthesized by Diels–Alder reactions between 2-vinylindoles 1 [22] as dienes and methyl 2-acetamidoacrylate (dehydroalanine) 2 [23] as dienophile (Scheme 1). Reported [4 + 2] cycloaddition reactions of methyl 2

• efficiency (Table 2, entry 4). As a consequence, we choose toluene as solvent for further cycloaddition reactions. Under these conditions, alkyl- (Table 2, entries 5 and 6) and aryl- (entries 7 and 8) substituted dienes smoothly react with methyl 2-acetamidoacrylate (2) affording the desired cycloadducts in

• and cheap reactant, whereas 2-vinylindoles can be easily synthesized by a common precursor [22]. Finally, by exploring the scope of the reaction and in connection with our previous reports on the cycloaddition reactions of 2-vinylindoles, we were able to point out several features about the reactivity

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• -alkoxyfurans by employing [4 + 2] and/or [4 + 3] cycloaddition reactions. Further, they used a RRM protocol in the presence of catalyst 2 to generate the spiroketal derivative 281 (Scheme 58). Ikoma and co-workers [59] have reported a short synthetic sequence to cis-fused heterocycles by employing the 7

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• unexpected as it is not known as a catalyst for azide–alkyne cycloaddition reactions [1][2]. Conclusion A tandem copper-catalyzed silyl deprotection/azide cycloaddition was developed for TIPS-protected tetrasubstituted propargylamines. These substrates are synthesized by a copper-catalyzed ketone–amine

Cross-metathesis reaction of α- and β-vinyl C-glycosides with alkenes

• Ivan Šnajdr,
• Kamil Parkan,
• Filip Hessler and
• Martin Kotora

Beilstein J. Org. Chem. 2015, 11, 1392–1397, doi:10.3762/bjoc.11.150

• cycloaddition reactions providing indolyl C-deoxyribosides [6], cyclopentenonyl C-deoxyribosides [9], triazolyl C-deoxyribosides [12][13], carboranyl C-deoxyribosides [7], and finally also in Diels–Alder reaction with cyclobutadiene derivatives [8]. Despite of the above mentioned transformations, alkynyl C

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• accomplished in a one-pot reaction under Wolff–Kishner reaction conditions to generate 223 and 259, respectively (Scheme 41). Cycloaddition reactions [2 + 2] Cycloaddition: Roemer and Lentz [175] have reported the synthesis of fluorinated ferrocenophanes from 1,10-bis(trifluorovinyl)ferrocene and 1,4-(1,10

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• formyl moieties. Keywords: acylnitrile oxide; amide; formylnitrile oxide; functionalized nitrile oxide; Weinreb amide; Introduction Nitrile oxides are valuable synthetic synthons for the construction of heterocyclic compounds by cycloaddition reactions, which lead to the formation of two bonds in a

• oxides. In our previous work, we reported the preparation of nitrile oxide 2 bearing an N-methylcarbamoyl group by treatment of 2-methyl-4-nitroisoxazolin-5(2H)-one (1) only with water at room temperature. Nitrile oxide 2 undergoes cycloaddition reactions with alkenes [4][5], alkynes (Scheme 1) [4][5

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• )pyrimidine (6), 4-(3-pyridyl)pyrimidine (7), and 4-(4-pyridyl)pyrimidine (8) as starting materials we managed to obtain new pyrrolo-fused derivatives by 1,3-dipolar cycloaddition reactions of their corresponding N-ylides in 1,2-epoxybutane as reaction medium and deprotonating agent. Pyrrolo[1,2-c]pyrimidines