(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

• catalyzed by the bifunctional urea 127 (Scheme 41) [61]. The transformation follows a Michael–Michael mechanism and is considered a formal [4 + 2] cycloaddition of 128 (bearing a nucleophilic carbon as well as an electrophilic carbon) and protected methylene-indolinones 129. A wide range of substrates were

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• role of the 6’-OH functionality is shown to be critical in the orchestration of the reaction process, as depicted in the proposed transition state model (Scheme 20). Cycloadditions The [4 + 2] cycloaddition of benzofuran-2(3H)-one derivatives 84 with methyl allenoate 85 to give the corresponding

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

• -catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small

• -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

• the complete deprotection of the cycloadducts in order to obtain the free amino acid function. Results 2-Vinylindole 1a was selected as a benchmark substrate to evaluate the feasibility of the devised [4 + 2] cycloaddition reaction with methyl 2-acetamidoacrylate (2). Test conditions and obtained

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

• , heteroaryl, and alkyl, etc. to produce α,β-unsaturated acylimidazolidinones 215. Next, the Evan’s asymmetric DA methodology involving a [4 + 2] cycloaddition of chiral bis(oxazoline) in the presence of Cu(OTf)2 was employed to furnish the required norbornene system 216. Later, it was converted into a lactam

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

• nitrate (40%, Scheme 56). Intramolecular Diels–Alder (DA) reaction: Suwa and co-workers [192] have synthesized the muscopyridine by a [4 + 2] cycloaddition of the bisketene 325. The condensation of acid dichloride derived from 323 with two molecules of Meldrum’s acid gave 324 which on thermal activation

• muscopyridine (73, 89%). [4 + 2] Cycloaddition (Diels–Alder reaction): In 2003, Tochtermann and co-workers [193] have synthesized a bis[10]paracyclophane with two chiral planes and one chiral axis via the DA reaction as a key step. The bifuran derivative 331 was subjected to a DA sequence with dimethyl

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

• -4,7-(ethylphosphinidene)indene (2e) only upon heating up to 60 °C. With further heating to 120 °C with N-phenylmaleimide, the cycloadducts 2a–c and 2e undergo the retro-Diels–Alder reaction and form only one product of the [4 + 2] cycloaddition reaction 3a–с, 3e with good yields up to 65%. Keywords

• 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

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• also been prepared using the anodic oxidation route. Possibly, one of the most important uses of the Shono oxidation has been in the development of the [4 + 2] cycloaddition, more commonly known as the Diels–Alder reaction for the controlled preparation of N-acyliminium ions to react with dienophiles

Design and synthesis of novel bis-annulated caged polycycles via ring-closing metathesis: pushpakenediol

• Sambasivarao Kotha and
• Mirtunjay Kumar Dipak

Beilstein J. Org. Chem. 2014, 10, 2664–2670, doi:10.3762/bjoc.10.280

• the corresponding 2,5-diallyl-1,4-benzoquinone (18) was obtained in good yield (67%). Since the quinone 18 is prone to polymerization (it gave a long streak on TLC when exposed to air at rt), it was immediately subjected to the [4 + 2] cycloaddition reaction with freshly prepared 1,3-cyclopentadiene

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• unit. Representative synthetic reactions of fullerene C60 (2) include cyclopropanation [29][30], [3 + 2] cycloaddition [31][32], [4 + 2] cycloaddition [33], nucleophilic addition [34], and radical addition reactions [35]. Two of the earliest and most widely used reactions, the Bingel–Hirsch reaction

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

• and Die & Mould Technology, School of Materials Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China and Department of Chemistry, Tokyo Gakugei University, Tokyo 184-8501, Japan 10.3762/bjoc.10.65 Abstract The [4 + 2] cycloaddition of o-quinodimethanes, generated

• to remarkable differences in chemical and electronic properties between these two classes of EMFs. Chemical functionalization of fullerenes enhances molecular properties and possible applications of fullerenes [1][4]. The [4 + 2] cycloaddition reaction is a useful chemical modification method because

• it enables to introduce a variety of addends and/or the combination of different functionalities on the fullerene [7]. Regarding the [4 + 2] cycloaddition of EMFs, however, no report is available for endohedral di-metallofullerenes, with the exception of azafullerene [8]. A limited number of reports

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

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• . In the case of methyl acrylate or acrylonitrile, a mixture of cis diastereomers was obtained regioselectively at higher temperature, in a 1:1.6 to 1:1.8 ratio. By contrast, the [4 + 2]-cycloaddition proved to be completely regioselective when performed on the catechol derivative in the absence of

• based on a first Diels–Alder cycloaddition, as shown above. However, a recent report of Norsikian, Beau and co-workers described a novel sequence of tandem transformations which combined the Petasis reaction, intramolecular [4 + 2]-cycloaddition, cross metathesis and Michael reaction. This process gave

• product showed traces of the boron cycloadduct, highlighting that this mechanism proceeds, first with a Lewis-acid catalysed [4 + 2]-cycloaddition, and then by Lewis acid-assisted C–B bond protonation. In a different approach which exploited another aspect of the reactivity of boron-substituted dienes

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• peroxides are based on three key reagents: oxygen, ozone, and hydrogen peroxide. These reagents and their derivatives are used in the main methods for the introduction of the peroxide group, such as the singlet-oxygen ene reaction with alkenes, the [4 + 2]-cycloaddition of singlet oxygen to dienes, the

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• allyl cation to the diene. Curiously, by using a gold(I) catalyst bearing a π-acceptor phosphite ligand, such as Au10/AgSbF6, allenedienes disubstituted at the distal position of the allene lead to products formally arising from a [4 + 2] cycloaddition process (Scheme 8, b) [59][60]. Several

• [4 + 2] cycloaddition (Scheme 9, R1, R2 = alkyl groups). This turned out to be the case and, gratifyingly, we showed that it is possible to perform highly enantioselective allenediene [4 + 2] cycloadditions by using gold complexes derived from a bulky phosphoramidite equipped with anthracenyl

• into a enantioselective version by using a novel chiral gold complex Au14, featuring a triazole unit embedded in a rigid axially chiral cyclic frame (Scheme 11) [72]. The catalyst generated from Au14 and AgNTf2 was able to promote the [4 + 2] cycloaddition between allenamides 16 and conjugated dienes

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• also observed in particular cases affording methylenecyclohexene derivatives like VI [14]. On the other hand, 1,6-enynes VII, bearing an aryl substituent at the alkyne, undergo a formal intramolecular [4 + 2] cycloaddition through an initial 5-exo cyclization followed by a Friedel–Crafts-type reaction

• acetylene moiety would take place through an initial 5-exo cyclization that in the case of aryl-substituted enynes (R = Ar) would give rise to a formal [4 + 2] cycloaddition product XIV [18][19], or alternatively, through a relatively less common 6-endo-dig pathway via gold species XV, which could be

• and 4a’, is generated in preference to 3a which would be the expected product derived from a formal [4 + 2] cycloaddition initiated by a 5-exo cyclization followed by a Friedel–Crafts-type process in intermediate 5a or 5a’, as described by Echavarren and co-workers [18][19]. Prompted by this result

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• for the aspired synthesis [10][11][12][13]. A classical synthesis was published in 1988 by Hansen where a silyl-substituted diene 3 was used for the [4 + 2]-cycloaddition (Scheme 1) [14]. Starting from bisquinone 4 the annulated ring system 5 is obtained in a 1:1 mixture of cis-endo regioisomers

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• been the subject of several theoretical investigations [7][8][9][10]. The necessary nitronic ester precursors are readily preparable by Lewis acid-promoted [4 + 2]-cycloaddition reactions of nitroalkenes with appropriate dienes, a general reaction first reported by Denmark and coworkers (Denmark Diels

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• ) units. The remaining methyl groups are believed to be installed by S-adenosyl methionine (SAM). An intramolecular Aldol condensation generates the pyrrolinone 62, which reacts via an [4 + 2]-cycloaddition to prochaetoglobosin I (63) [56]. Recently, gene disruption studies of Chaetomium globosum revealed

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

• Jungho Jun,
• Hyu-Suk Yeom,
• Jun-Hyun An and
• Seunghoon Shin

Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198

• = di-t-butyl-o-biphenylphosphine, JohnPhos) formed in situ was used as catalyst, the reaction was more efficient in chlorinated solvents rather than polar aprotic or aromatic hydrocarbon solvents (Table 1, entries 1–7). Contrary to the previous [4 + 2] cycloaddition, formal enyne cross metathesis or [2

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• method of Tiecco [32]. Pyrazole 3g was then synthesized by the reaction with hydrazine hydrate. AZg was obtained by the Diels–Alder [4 + 2]-cycloaddition with cyclopentadiene and hydrogenation using PtO2 as a catalyst. The endo-configured structure of azoalkanes AZc–g was determined by X-ray

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• developed as the most powerful synthetic routes to construct oxygen or nitrogen-containing six-membered heterocycles [4][5][6][7][8]. In recent years, the imine Diels–Alder reaction (also known as Povarov reaction) and the [4 + 2] cycloaddition reaction of imines (obtained from the corresponding aromatic

Asymmetric Brønsted acid-catalyzed aza-Diels–Alder reaction of cyclic C-acylimines with cyclopentadiene

• Magnus Rueping and
• Sadiya Raja

Beilstein J. Org. Chem. 2012, 8, 1819–1824, doi:10.3762/bjoc.8.208

• optically active aza-tetracycles in good yields with high diastereo- and enantioselectivities under mild reaction conditions. Keywords: BINOL phosphate; [4 + 2] cycloaddition; Diels–Alder reaction; organocatalysis; Introduction The enantioselective aza-Diels–Alder reaction is an important method for the

Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides

• Andrew Tigchelaar and
• William Tam

Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201

• solvent resulted in incomplete reaction after 3 h, so the most efficient reaction conditions for the intramolecular [4 + 2] cycloaddition of diene-tethered alkynyl bromide 1a were found to be [IrCl(COD)]2 (2 mol %), dppe (4 mol %) in DMSO at 90 ºC. In order to illustrate the general applicability of this

• the starting material was recovered. Changing the reaction conditions to the original system of Vaska’s complex in toluene (conditions B, Scheme 5) did not change this result. The previous Ir-catalyzed [4 + 2] cycloaddition work by Shibata and co-workers did not include any examples of similar

• found to undergo [4 + 2] cycloaddition under the reported conditions. The Ir-catalyzed reactions provided the cycloadducts in similar yields to the previous Rh-catalyzed reactions of alkynyl halides; however, the Ir-catalyzed reactions required higher reaction temperatures (90 versus 25 °C). Literature

Highly enantioselective access to cannabinoid-type tricyles by organocatalytic Diels–Alder reactions

• Stefan Bräse,
• Nicole Volz,
• Franziska Gläser and
• Martin Nieger

Beilstein J. Org. Chem. 2012, 8, 1385–1392, doi:10.3762/bjoc.8.160

• used method [3][4][5][6][7]. Some examples are shown in Figure 1. The first application was the total synthesis of the steroid Cortisone (1) in 1952 by Woodward et al. [8]. Another example, indicating the importance of the well-known [4 + 2] cycloaddition in natural-product synthesis, is the first

• published total synthesis of Taxol (2) by Nicolaou. Two different [4 + 2]-cycloaddition reactions were applied to set up each of the two six-membered rings of the target molecule [9][10]. As a final example, Dynemicin A (3) should be mentioned, which is an enediyne consisting of a complex heterocyclic

• skeleton and a network of sensitive functional groups, exhibiting antitumor and antibiotic activity [11]. Three independent research groups (Schreiber, Myers and Danishefsky) successfully applied [4 + 2]-cycloaddition reactions in elegant and divergent strategies to reach the target molecule [12][13][14

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• ] utilizing both Cu(I) and Pt(II) [19] catalysts afforded the desired cyclopropane 6 in moderate yield (40%) along with ketone 7 (45%), derived from [4 + 2] cycloaddition of the benzopyrylium intermediate with the pendent alkyne [20] (Scheme 2b). However, better yields were observed when the initial