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

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• -directed synthesis of Z-alkenes. Scope of the phenol-directed Z-alkene synthesis. Rationale for the formal [3 + 2] cycloaddition. Scope of the formal [3 + 2] cycloaddition. Benzylation of styrenes using copper catalysis. Copper-catalyzed carboiodination of alkynes. Copper-catalyzed trans-carbohalogenation

• + 2] cycloaddition of styrenes and α-bromo keto esters. Using this method, various substituted dihydrofurans were produced in high yields (Scheme 15). Electron-rich and electron-poor styrenes as well as alkyl and aryl keto esters were combined to provide diversely substituted dihydrofurans. The

• alkenylation reactions. However, the product of addition of a secondary bromo keto ester possesses an acidic α-proton. This proton can be deprotonated by diisopropylamine, and the resulting enolate cyclizes onto the newly formed benzylic halide to form the dihydrofuran (Scheme 14). This method is formally a [3

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• Since the discovery in 2002 that copper(I) could catalyze the Huisgen alkyne–azide [3 + 2] cycloaddition with high selectivity for the 1,4-triazole [1][2], the so-called copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) has become a privileged reaction which is widely employed in all areas of the

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• and Meyer–Schuster rearrangement 6-prenoylindole was synthesized and reductively dimerized to a cyclopentane in a [3 + 2] cycloaddition by treatment with SmI2 in THF. From 4-iodoindole, the natural product indiacen B from the myxobacterium Sandaracinus amylolyticus was synthesized for the first time

• Nicolaou and Procter [31][32]. The pattern of geometrical [3 + 2] cycloaddition was also obtained with inverted enone moieties. 6-Prenoylindole (14) was synthesized in two steps from 6-iodoindole (4) by Sonogashira coupling with propargylic alcohol 12 and subsequent Meyer–Schuster rearrangement [33

• . Meyer–Schuster rearrangement of 13 and SmI2-mediated reductive [3 + 2] cycloaddition, followed by elimination to cyclopentene 16. Selected NOESY correlations for compound 15 are given. Nazarov-type cyclization of 14 to cyclopentanones 17 and 18; synthesis of verticillatine B (20). Synthesis and X-ray

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

• (Scheme 51). [3 + 2] Cycloaddition (1,3-dipolar cycloaddition/click reaction): In 2010, Raghunathan and co-workers [185] have synthesized a C2-symmetric triazolophane by a copper(I)-catalyzed azide-alkyne cycloaddition, involving a click reaction. The dipropargyl fluorenyl derivative 299 was prepared from

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• -pot reaction over three steps in 25%. By diazotization of 1d and trapping the salt with TMS-azide, we obtained azido azobenzene 1e in 63% yield through a [3 + 2] and retro-[3 + 2] cycloaddition (Scheme 1b) according to the procedure of Barral et al [10]. For the Mills reaction, different nitroso

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• the H-4a proton that resonates at 2.18 ppm as a doublet of doublet of doublets. 5’-Azido-2’-oxa-3’-aza-4’a-carbanucleosides 11 and 12 were independently engaged in a CuI-catalyzed Huisgen [3 + 2] cycloaddition reaction with a series of substituted alkynes 17, according to the procedure described by

• formation of viral plaques or virus-induced cytopathogenicity by 50% is expressed as EC50. Conclusion In summary, starting from 5’-azido-2’-oxa-3’-azanucleosides, a new series of C-5’-triazolyl-2’-oxo-3’-aza-4’a-carbanucleosides has been synthesized by using a CuI-catalyzed Huisgen [3 + 2] cycloaddition

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• couplings [13][14], and photooxygenation reactions [15][16]. Similarly, Zheng has reported oxidatively initiated indole synthesis [17] and [3 + 2] cycloaddition [18][19] reactions using photocatalyst 2. Finally, a variety of transition metal complexes bearing bipyrazyl ligands have been prepared and

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

• C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane. Keywords: cycloaddition; fluorine; pentafluoroethyl group; pentafluoroethyldiazomethane; pyrazole; Introduction Incorporation of fluorinated fragments into organic compounds might affect their

• -dicarbonyl compounds (or their synthons) with hydrazines [39][40][41][42][43][44]. In this context, novel practical methods to C2F5-pyrazoles are needed. Last year, Ma and colleagues synthesized CF3-pyrazoles by [3 + 2] cycloaddition between in situ generated CF3CHN2 and alkynes [45]. This method, however

• with C2F5CHN2 to give only 3,5-disubstituted pyrazoles. Formation of 3,4-disubstituted isomers was observed. Disubstituted alkynes behaved differently, because of controversial electronic and steric effects. According to the orbital symmetry rules, the [3 + 2] cycloaddition must lead to pyrazoles with

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• methodology is more convenient to produce the complex polycyclic molecules in a simple way. Keywords: copper(II) acetate; decarboxylative CuAAC; dehydrogenative coupling; fused triazoles; one-pot synthesis; Introduction The copper-catalyzed Huisgen [3 + 2] cycloaddition (or copper-catalyzed azide–alkyne

• several advantages over the classical C–C bond formation method including the stability and preparation of the starting material and the non-hazardous byproducts. In 2011, Kolarovič et al. [6] first reported the copper-catalyzed decarboxylative [3 + 2] cycloaddition reaction of 2-alkynoic acid with

• formation of 4 is described in Scheme 5. Initially alkynoic acid 2 undergoes decarboxylation to form the copper acetylide (A) in the presence of the Cu+ catalyst which is generated by the reduction of Cu2+ with sodium ascorbate. The obtained copper acetylide undergoes regioselective [3 + 2] cycloaddition

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

• Gynecology, Jiangxi Provincial people's Hospital, Nanchang, Jiangxi 330006, P. R. China 10.3762/bjoc.10.238 Abstract An efficient one-pot tandem cyclization/[3 + 2] cycloaddition reaction of N’-(2-alkynylbenzylidene)hydrazides with ethyl 4,4,4-trifluorobut-2-ynoate under silver triflate-catalyzed or

• electrophile-mediated conditions is described. Various trifluoromethylated pyrazolo[5,1-a]isoquinolines were afforded in moderate to excellent yield by this developed method. Keywords: [3 + 2] cycloaddition; electrophile; N’-(2-alkynylbenzylidene)hydrazide; silver triflate; tandem; Introduction Isoquinolines

• reaction of N’-(2-alkynylbenzylidene)hydrazides 1a (0.3 mmol) and ethyl 4,4,4-trifluorobut-2-ynoate (2, 0.6 mmol) using NaOAc (0.45 mmol) as base, in the presence of AgOTf (5 mol %) and 4 Å MS (75 mg) in CH2Cl2 (3 mL) at room temperature overnight. Surprisingly, the unexpected [3 + 2] cycloaddition product