Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• ][1,4]diazepinium salts 10 and the related neutral, free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium intermediates 14

• ][26][27][28][29][30]. Over the past years, we have been engaged in the synthesis of novel 1,2,4-triazolo heterocycles annulated to benzoazepine or heteroazepine derivatives by a tandem [3+ + 2]-cycloaddition/rearrangement between 1-aza-2-azoniaallenium ions with nitriles [31][32][33][34]. In the [3

• , we wish to describe the synthesis of unprecedented tricyclic heterocycles, i.e., 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral free base derivatives 13 via the cationic [3+ + 2]-cycloaddition/rearrangement reactions using the bicyclic 4-acetoxy-4-azo

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• mechanism that first involves the formation of a 2’-iodobiphenyl-2-azide promoted by the copper complex. The latter then catalyzes an intermolecular [3 + 2] cycloaddition with the alkyne. Finally, the copper-triazole moiety inserts intramolecularly into the second Ar–I bond, allowing a ring closure after

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• Veronika Hladikova Jiri Vana Jiri Hanusek Institute of Organic Chemistry and Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic 10.3762/bjoc.14.113 Abstract This review covers all known examples of [3 + 2]-cycloaddition between sydnones and both terminal as well

• regioselectivity. Keywords: alkynes; Cu(I) catalysis; [3 + 2]-cycloaddition; mechanism; regioselectivity; sydnones; Review Introduction Since Huisgen’s discovery of the [3 + 2]-cycloaddition between 3-substituted sydnones and both terminal as well as internal alkynes [1][2] many researchers have tried to utilize

• bicyclic intermediate via a concerted [3 + 2]-cycloaddition followed by its very fast decomposition (extrusion of CO2) via a retro-Diels–Alder [4 + 2]-cycloaddition. The almost spontaneous extrusion of CO2 is caused by an energetically favorable aromatization occurring in this step leading to the formation

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• (Scheme 5) [42]. In the absence of light, azobenzene derivatives were isolated as the pure E-isomers. In their original report, Sharpless and co-workers described the use of copper turnings to promote a regioselective azide–alkyne [3 + 2]-cycloaddition ("click") reaction over 24 hours [43]. High-speed

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• -dithioacetals [4] are of particular interest as attractive nucleophiles for the addition to halonium ions [5][6], acyl chlorides [7] and other electrophiles [8][9][10] and are broadly used as precursors for [2 + 2]-cycloaddition [11][12], (aza)-Diels–Alder reaction [13][14], and [3 + 2]-cycloaddition reactions

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• mechanisms. The in situ generated sterically crowded thiocarbonyl S-methanide 16b in dry THF undergoes a [3 + 2]-cycloaddition with both E- and Z-1b forming mixtures of diastereoisomeric thiolanes 19b [19] (Scheme 9). However, in all studied cases, the configuration of the starting dipolarophile was

• - and Z-1b, and depending on the substitution pattern of the aziridine ring, the formation of the pyrrolidine derivative 34 occurred either with complete stereoselectivity or mixtures of isomeric products were obtained. The [3 + 2]-cycloaddition of the azomethine ylide E,Z-32a, formed via conrotatory

• . Stepwise [3 + 2]-cycloadditions of dimethyl dicyanofumarate (E-1b) and dimethyl dicyanomaleate (Z-1b) with the in situ generated azomethine ylides 32. [3 + 2]-Cycloaddition of diazomethane with dimethyl dicyanofumarate (E-1b) leading to 1H-pyrazole derivative 36. Reversible Diels–Alder reaction of fulvenes

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• . Unfortunately, the reaction is complicated by a concurrent [3 + 2]-cycloaddition of diazo compounds 96 to nitrosoalkenes leading to N-nitrosopyrazoles 98 via intermediates 99. A substantial improvement of this isoxazoline ring-forming strategy was recently introduced by Li et al. [85], who achieved the

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

• Grzegorz Mlostoń,
• Paulina Pipiak,
• Róża Hamera-Fałdyga and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185

• applied [14]. Another approach, which opens access to diverse ethenes, is the ‘two-fold extrusion reaction’, which comprises the [3 + 2]-cycloaddition of a diazo compound with a thiocarbonyl dipolarophile and subsequent elimination of N2 followed by sulfur extrusion [15][16][17]. In our continuing studies

• unsuccessful. The results obtained with thiofluorenone (1c) prompted us to prepare other 2-trimethylsilylated 1,3-dithiolanes of type 6, available via [3 + 2]-cycloaddition of the in situ generated (at ca. −45 °C) silylated thiocarbonyl S-methanide 10 with thioketones 1a,c,d,h and i. The obtained products of

• -trimethylsilyl-4,4,5,5-tetraaryl-1,3-dithiolanes, readily available by treatment of hetaryl thioketones with trimethylsilyl diazomethane (TMS-CHN2), are superior substrates for the preparation of tetraarylethenes. Another group of 2-trimethylsilylated 1,3-dithiolanes, obtained through the [3 + 2]-cycloaddition

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• other methods mostly provide the products in times above 60 minutes [33][34][36]. Conclusion In summary, we have described the use of sonochemistry in the organocatalytic enamine–azide [3 + 2] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These sonochemical promoted reactions were

• Biotechnology of Natural and Synthetic Products, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil Departamento de Quimica Organica, Universidad de Cordoba, Campus de Rabanales, Cordoba, Spain 10.3762/bjoc.13.68 Abstract The use of sonochemistry is described in the organocatalytic enamine–azide [3 + 2

• ] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These sonochemically promoted reactions were found to be amenable to a range of 1,3-diketones or aryl azidophenyl selenides, providing an efficient access to new ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones in good to excellent yields and

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• case of similar thiocarbonyl S-isopropanides, the intermediate zwitterions, formed in the course of the attempted [3 + 2]-cycloaddition with electron-deficient ethenes, undergo 1,3-electrocyclization yielding mixtures of stereoisomeric cyclopropanes in addition to the expected 5-membered thiolanes

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• cyano group activates the [3 + 2] cycloaddition of azomethine ylides and is then removed to yield 5-unsubstituted pyrrolidines [74]. These substructures appear in several biologically active natural products and drugs [75]. A range of decyanation conditions were screened such as NaBH4 in THF or MeOH

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

• stereospecific cyclic adducts. Keywords: L-proline; ninhydrin; sarcosine; spiropyrrolidine; 5-vinylindazole; 5-vinylindole; Introduction The [3 + 2] cycloaddition between azomethine ylides and olefins/acetylene as dipolarophiles is an important reaction to access a number of novel heterocyclic spiro scaffolds

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

• -5-substituted isoxazoles that are otherwise difficult to obtain. Keywords: β-azolyl enamine; [3 + 2]-cycloaddition; isoxazole; isoxazoline; nitrile oxide; Introduction The biological activity and technically useful properties of isoxazoles have made them the focus of both medicinal and materials

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

• , NH 03435, USA 10.3762/bjoc.12.211 Abstract The one-pot [3 + 2] cycloaddition of an azomethine ylide with a maleimide followed by another [3 + 2] cycloaddition of an azide with the second maleimide gives a 1,5-diamino intermediate which is used for a sequential aminomethylation reaction with

• formaldehyde through [5 + 1] annulation to afford a novel polycyclic scaffold bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide in stereoselective fashion. Keywords: [5 + 1] annulation; [3 + 2] cycloaddition; one-pot reactions; stereoselective synthesis

• new sequence initiated with a three-component [3 + 2] cycloaddition for preparing polycyclic scaffold 1 bearing tetrahydroquinazoline, pyrrolidine, pyrrolidinedione, and N-substituted maleimide rings. Those heterocyclic fragments could be found in bioactive compounds such as bromodomain, thrombin

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

• . Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. Keywords: [3 + 2] cycloaddition; asymmetric reaction; catalytic reaction; low catalyst loading

• , relatively high catalyst loadings (0.5–25 mol %) are required to achieve high yield and selectivities [15][45]. First, we investigated the catalytic asymmetric [3 + 2] cycloaddition of Schiff base 1a, prepared from glycine methyl ester and benzaldehyde, with N-phenylmaleimide (2a) in the presence of CuN

• revealed that the reaction proceeded with 0.01 mol % loading of chiral CuHMDS catalyst without significant loss of selectivity (Table 1, entry 11). We then examined the substrate scope of the [3 + 2] cycloaddition with respect to the Schiff base (Table 2). The Schiff bases prepared from tolualdehydes were

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• 1,5-diradical as a key intermediate. The complete change of the reaction mechanism toward the concerted [3 + 2]-cycloaddition was observed in the reaction of a sterically crowded cycloaliphatic thiocarbonyl ylide with ferrocenyl methyl thioketone. Keywords: [3 + 2]-cycloadditions; 1,3-dithiolanes

• Hz. After chromatographic purification, the 13C NMR spectrum confirmed the 5-CH2-type of the 1,3-dithiolane 6m, as the corresponding CH2 absorption was found at 52.5 ppm (Scheme 3). Based on our earlier interpretation of the reaction mechanism leading to 1,3-dithiolanes via [3 + 2]-cycloaddition of

• key-intermediates in the reaction. On the other hand, the formation of 1,3-dithiolanes of type 5 in reactions with cycloaliphatic thiocarbonyl S-methanides competes with the concerted [3 + 2]-cycloaddition leading to the sterically less crowded 1,3-dithiolanes 6 (Scheme 2). These results demonstrate

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

• enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with α,β-unsaturated aldehydes has been developed. Keywords: [3 + 2] annulation; enals; synergistic catalysis; vinylcyclopropanes

• ; 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

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• clarity. Two independent molecules exist in the asymmetric unit, one of them is shown. Copper-catalyzed [3 + 2] cycloaddition of 1 with organic azides 2. Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), Cu cat. (0.025 mmol). Isolated yield are shown. Possible mechanism. Reaction of 3a with HCl, I2 and

• University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan 10.3762/bjoc.12.123 Abstract Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2

• ] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. Keywords

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

• prepare phosponylpyrazoles 217 in the presence of KOH in MeOH in 73–95% yields (Scheme 44) [82]. Based on their explanation, the treatment of dimethyldiazomethylphosphonate 213 with a nucleophilic base generates diazo compound 215. The subsequent [3 + 2] cycloaddition reaction of 215 with Knoevenagel

• shift, aromatized to vinylpyrazoles 234. Recently, the [3 + 2] cycloaddition of phosphonate azomethine ylides 235 with ynones 236 to give substituted 1H-pyrrol-2-ylphosphonates 237 has been described by Yu et al. (Scheme 48) [86]. The desired 1H-pyrrol-2-ylphosphonate 241 could also be obtained through

• via the [3 + 2] cycloaddition of phosphonate azomethine ylides with ynones. Three-component synthesis of 1H-pyrrol-2-ylphosphonates. The classical Reissert reaction. One-pot three-component synthesis of N-phosphorylated isoquinolines. One-pot three-component synthesis of 1-acyl-1,2-dihydroquinoline-2

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

• (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the

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

• -workers also established a CPA (cat. 38)-catalyzed asymmetrc [3 + 2] cycloaddition of 3-indolylmethanols with 3-methyl-2-vinylindoles, affording spiro[cyclopenta[b]indole-1,3’-oxindole] scaffolds in moderate to good yields (72–99% yield) and with excellent diastereoselectivities (>95:5 dr) and

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• blocks in synthetic organic chemistry. Recently, they have attracted also strong interest for applications in materials science and chemical biology [1]. One of the most important transformations of alkynes is the copper-catalyzed [3 + 2] cycloaddition with azides, which can be performed under mild

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

• products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S bond. The latter decompose only at higher temperature (ca. −40 °C) to generate thiocarbonyl S-isopropanide. In the absence of the starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via

• -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

• diradical mechanism postulated for the formal [3 + 2]-cycloaddition of aryl/hetaryl thioketones 1 with the in situ generated thiocarbonyl S-methanides [28]. The missing formation of dimers from thiocarbonyl ylides 3 derived from hetaryl thioketones can be explained by steric hindrance resulting from the

Enantioselective [3 + 2] annulation of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines catalyzed by a bifunctional dipeptide phosphine

• Huanzhen Ni,
• Weijun Yao and
• Yixin Lu

Beilstein J. Org. Chem. 2016, 12, 343–348, doi:10.3762/bjoc.12.37

• phosphine catalyst furnishes the final [3 + 2] annulation product 5. Conclusion In conclusion, we have described the first enantioselective [3 + 2] cycloaddition of α-substituted allenoates with β,γ-unsaturated N-sulfonylimines, catalyzed by amino acid-derived bifunctional phosphines. The [3 + 2] annulation

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• were not successful. The dimethyl maleate derivative was formed but was accompanied by the [3 + 2] cycloaddition product 22. With excess of diazomethane, clean and efficient formation of 22 was observed (Scheme 9). Acid 4 was stable in water, methanol, isopropylalcohol, boiling benzene, or boiling