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

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• offers some advantages, especially in the case of cycloaddition reactions [18]. To the best of our knowledge, reactions of thioketones under high-pressure conditions have never been studied. After a series of optimization experiments, a solution of 1a and 2a in a molar ratio of 1:2 in toluene was placed

On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

• Andrey S. Mereshchenko,
• Alexey V. Ivanov,
• Viktor I. Baranovskii,
• Grzegorz Mloston,
• Ludmila L. Rodina and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2015, 11, 504–513, doi:10.3762/bjoc.11.57

• of DDC 1 with thiobenzophenone (2a). Reactions of the intermediate thiocarbonyl ylide 7'd via competative 1,5-EC (a) or 1,3-EC (b) followed by desulfurization of thiirane 4'd into alkene 5'd. Calculated relative energies (in kcal·mol−1) and relative reaction rates for cycloaddition reactions of diazo

Functionalized branched EDOT-terthiophene copolymer films by electropolymerization and post-polymerization “click”-reactions

• Miriam Goll,
• Adrian Ruff,
• Erna Muks,
• Felix Goerigk,
• Beatrice Omiecienski,
• Ines Ruff,
• Rafael C. González-Cano,
• Juan T. Lopez Navarrete,
• M. Carmen Ruiz Delgado and
• Sabine Ludwigs

Beilstein J. Org. Chem. 2015, 11, 335–347, doi:10.3762/bjoc.11.39

• on the reaction with the monomer EDOT-N3 and obtained the product EDOT-clickSO3Na in high yield. For 1H NMR and IR-spectra we refer to Figure S3 and Figure S4 in Supporting Information File 1. Figure 3A depicts the synthesis of the cycloaddition-reactions of the copolymer films P(EDOT-N3-co-3T)-1:1

Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

• Almaz Zagidullin,
• Vasili Miluykov,
• Elena Oshchepkova,
• Artem Tufatullin,
• Olga Kataeva and
• Oleg Sinyashin

Beilstein J. Org. Chem. 2015, 11, 169–173, doi:10.3762/bjoc.11.17

• (R = CN, COOEt, OMe, CH2OEt) results in corresponding 1-alkyl-3,4,5-triphenyl-1,2-diphospholes (alkyl = CH2CN (1a), CH2COOEt (1b), CH2OMe (1c), and (CH2)2OEt (1d)), which spontaneously undergo the intermolecular [4 + 2] cycloaddition reactions at room temperature to form the mixture of the

• , phosphinidenes, etc. [2]. At the same time, the presence of electron-withdrawing substituents (cyano-, alkoxy-, or halo-) at the phosphorus atom reduces the aromaticity of the monophosphole ring and facilitates cycloaddition reactions resulting in novel 7-phosphanorbornenes [5][6], which was verified by

• at room temperature for a few hours. 1,2-Diphosphole 1d is more stable and no cycloaddition was observed upon heating in toluene. Upon standing, the diphospholes 1a–c undergo spontaneous [4 + 2] cycloaddition reactions leading to a mixture of cycloadducts (Scheme 2). The 31P NMR spectra of the

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• (i.e., RBIT, NBF-Cl, FITC) or nucleophilic fluorescent dye (i.e., coumarin) into the polymers, respectively. The key intermediate azido-modified polymers have been used as precursor of the amino-modified polymers, but they can be considered as versatile substrates for cycloaddition reactions as well

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

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• 0.15 mmol g−1 for the Diels–Alder reaction of the non-functionalized ortho-quinodimethane [11] proves that a significantly increased grafting is observed using the pyrazine derivative. So far, the reported cycloaddition reactions of ortho-quinodimethanes leading to the grafting of aromatic rings by

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

• -benzylbenzimidazoles, phenacyl bromides and non-symmetrical activated alkynes in presence of propenoxide or 1,2-epoxybutane used as acid scavenger and reaction solvent [16]. These results prompted us to further investigate 1,3-cycloaddition reactions of 1-substituted 3-(alkoxycarbonylmethyl)benzimidazolium ylides with

• various dipolarophiles under the same reaction conditions, aiming to explore the generality of the reaction. The previously reported data on 1,3-cycloaddition reactions of 1-substituted 3-(alkoxycarbonylmethyl)benzimidazolium ylides with various dipolarophiles are rather contradictory. Thus, 1-alkyl-3

• cycloadducts 8. In order to explain the above mentioned results, we investigated the influence of reaction conditions on the ratio of the final reaction products 4 and 5 in 1,3-dipolar cycloaddition reactions of the 1-benzyl-3-(ethoxycarbonylmethyl)benzimidazolium bromide 6 (R = H, R1 = benzyl) with ethyl

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• 13C NMR, HRMS, as well as X-ray diffraction analysis (Figure 1, for details, see Supporting Information File 1). Based on this one-pot tandem electrophilic cyclization/[3 + 2] cycloaddition reactions, highly functionalized pyrazolo[5,1-a]isoquinolines can be obtained via palladium-catalyzed cross

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• ]. Various methodologies and new synthetic approaches for their preparation and reactivity have been reviewed [3]. Continuing our long-standing interest for photochemical intramolecular cycloaddition reactions of various β-heteroaryl-o-divinylbenzenes, furans [4][5][6], thiophenes [6][7][8], pyroles [9][10

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• these compounds (17, 18 and 19) was prepared in our laboratories by a combination of Diels–Alder cycloaddition and 1,3-dipolar cycloaddition reactions [21]. We found that the Raney nickel-mediated cleavage took place readily on 17 to yield a β-hydroxyketo-functionalized 7-oxanorbornane 20 (Scheme 3

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• has been established that the construction of well-defined multivalent, anomerically pure 3-amino-2,3-dideoxyneoglycoconjugate architectures was successfully achieved by using cycloaddition reactions of alkynes and azides. It is expected that this strategy will find extensive applications in

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• electron spin traps [1] and in cycloaddition reactions [2]. As nitrones undergo 1,3-dipolar cycloadditions under mild conditions with a variety of unsaturated substances with a catalyst [3][4] or without a catalyst [5] they are important for the synthetic accessibility of five-membered heterocycles

Thermodynamically stable [4 + 2] cycloadducts of lanthanum-encapsulated endohedral metallofullerenes

• Yuta Takano,
• Yuki Nagashima,
• M. Ángeles Herranz,
• Nazario Martín and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2014, 10, 714–721, doi:10.3762/bjoc.10.65

• describe other EMFs [4][9][10]. Moreover, the only precedent of [4 + 2] cycloadducts of the fullerenes which have an open-shell electronic structure of the cage, e.g., La@C82, are thermodynamically unstable and show retro-cycloaddition reactions [10][11]. In addition, boat-to-boat inversion of the addend

• [5,6]-isomers, are allowed to be formed by cycloaddition reactions. (Please note that “site-isomer” refers to an isomer of the adducts which has the same fullerene and addend but different addition position – a classification proposed recently for fullerene’s chemistry by Martin et al. [14]). Therefore