One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• Diels–Alder reaction. Ghosh’s group reported an exclusive peri-, regio-, and stereoselective cycloaddition reaction of 5H-benzo[7]annulen-5-one (Scheme 35) [137]. The intermolecular [4 + 2] cycloaddition of 2,3-benzotropone (12) with cyclopentadiene (202) in the presence of boron trifluoride occurred

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• adducts. Due to the important pharmacological activities of these reactive o-QM intermediates, special attention is paid to the biological activity of these compounds. Keywords: aminophenols; [4 + 2] cycloaddition; dienophile; Mannich reaction; ortho-quinone methide; Review Introduction The Mannich

• at 78 °C, [4 + 2] cycloaddition took place between the o-QM generated from the corresponding aminonaphthol as diene component and cyclic imines playing the role of heterodienophiles (Scheme 5). Fülöp and co-workers then extended their studies by applying both 2-aminoalkyl-1-naphthols and 1-aminoalkyl

• intermediate 3. Asymmetric syntheses of triarylmethanes starting from diarylmethylamines. Proposed mechanism for the formation of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyrans 32. Cycloadditions of isoflavonoid-derived o-QMs and various dienophiles. [4 + 2] Cycloaddition reactions between

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• laboratory scale with high yields, from affordable, commercially available starting materials. Keywords: [4 + 2] cycloaddition; Diels–Alder; isobenzofuran; trapping reagent; Introduction Isobenzofurans have been described as the most reactive dienes for Diels–Alder reactions [1][2][3][4][5]. Their high

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• , sensing and display applications [41]. 4-Phenylnaphtho[2,3-c]furan-1,3-diones can well serve as reactive intermediates in multicomponent reactions, e.g., for synthesizing the corresponding imides. A particularly intriguing access to 4-phenylnaphtho[2,3-c]furan-1,3-diones is the intramolecular [4 + 2

• ]-cycloaddition of phenylpropiolic acid anhydrides. Usually, this synthesis requires harsh reaction conditions starting from phenylpropiolic acids [42][43]. However, employing bis(2-oxooxazolidin-3-yl)phosphinic chloride as an activating agent represents a suitable access [44]. Alternative approaches include the

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

• substituents were formed. Polycyclic products 35 were prepared through a concerted [4 + 2]-cycloaddition of E-1a with thiophene-functionalized fulvenes 36 [42] (Scheme 12). These cycloadducts are reported to undergo reversible intramolecular photocyclization to give products of type 37. The formation of the

• observed by 1H NMR spectroscopy [8]. Similar systems were prepared on solid phase and used as a new molecular recognition system [44]. The [4 + 2]-cycloaddition reactions of E- and Z-1b with electron-rich 1,3-dienes have been studied extensively by Sustmann and collaborators. Thus, 1-methoxybuta-1,3-diene

• carried out [45][48][50][51]. A stepwise reaction has also been suggested for the formal [4 + 2]-cycloaddition of E- and Z-1b with ethyl prop-1-enyl ether leading to a mixture of the corresponding 3,4-dihydro-2H-pyran and cyclobutane derivatives in a non-stereospecific manner [31]. A mechanism with the

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

• -bromooxime 26 with lithium enolate 27 to give oxime 28 via the Michael addition to transient nitrosoalkene NSA6 [31]. Oxime adduct 28 existed predominantly in a cyclic 1,2-oxazine form (Scheme 11). Subsequent benzylation of oxime 28 and the thermal retro-[2 + 2]/[4 + 2]-cycloaddition cascade followed by

• oximes 67 and 68 can occur not only via an SEAr mechanism, but also through an alternative [4 + 2]-cycloaddition/elimination pathway (for cycloaddition chemistry of nitrosoalkenes see reviews and accounts: [6][7][8][9][10][57][58]). In the recent work by Palacios and co-workers, the reaction of

• suggest that the [4 + 2]-cycloaddition process (2) is thermodynamically favored for nitrosoalkenes bearing electron-donating group R, whereas the presence of an electron withdrawing group at the same position promotes the electrophilic substitution pathway (1). Pinho e Melo and co-workers developed a one

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• the D-series thiopeptides have been explored, (i) the late-stage construction of the pyridine core through [4 + 2] cycloaddition reaction flanked with the main difficulties to prepare the dienophile and alkene bearing the adequate thiazolyl moieties or (ii) the direct connection and construction of

• within five Hantzsch thiazole building steps [14]. Nicolaou and Moody reported then the synthesis of the heterocyclic core of GE2270 by using a late-stage [4 + 2] cycloaddition of a sophisticated bithiazolylazadiene with alkynylated thiazole [15][16]. As highly innovative strategy, Bach reported in 2005

• of thiopeptides GE2270 in which the macrocylization and heterocyclic core was simultaneously achieved through a late-stage Negishi cross-coupling [18][19]. Last year, Yamaguchi’s group proposed a novel elegant [4 + 2] cycloaddition Kondrat’eva reaction between a 2-alkenylated thiazole-4-carboxylate

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• . Results and Discussion We set out to synthesise two diene substrates for a photochemical [4 + 2]-cycloaddition with singlet oxygen to provide two different endoperoxides (Scheme 1, n = 1–2). Based on literature precedent Boc-protection was utilised for the amino group (Scheme 2) [13][14]. Moreover, the

• Herein, we report the development of a synthetic strategy using [4 + 2]-cycloaddition reactions to yield endoperoxides 18–23 that contain a protected primary amine. Such intermediates serve as useful new building blocks for organic synthesis. Preliminary exploration of the chemistry of these compounds

• endoperoxide synthesis. TBA-Cl = tetrabutylammonium chloride, NCS = N-chlorosuccinimide. Synthesis of endoperoxides 17–19 by [4 + 2]-cycloaddition of dienes 14–16 with singlet oxygen. The photochemical reactor was modified with a gas inlet fitted with a filter at the bottom of the reactor, and the original

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• ranged from 1:2 to 2:3 with a preference to 310a–315a regioisomers. An interesting approach to the synthesis of 1-indanones and 1-indenones is based on the hexadehydro-Diels–Alder (HDDA) reaction in which an alkyne reacts in the [4 + 2] cycloaddition with diyne and forms a reactive benzyne species as a

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• thorough literature search using Reaxys indicates that cyclohexanone has been made by [5 + 1] and [4 + 2] cycloaddition strategies thus validating the patterns of assembly shown in the third and fourth entries of Scheme 1 and the fourth entry of Scheme 2. The [5 + 1] literature examples involved insertion

Highly chemo-, enantio-, and diastereoselective [4 + 2] cycloaddition of 5H-thiazol-4-ones with N-itaconimides

• Shuai Qiu,
• Choon-Hong Tan and
• Zhiyong Jiang

Beilstein J. Org. Chem. 2016, 12, 2293–2297, doi:10.3762/bjoc.12.222

• chemoselectivity and excellent yield of 98% (Table 1, entry 10). With the optimal reaction conditions in hand, we examined the substrate scope of the enantioselective [4 + 2] cycloaddition between 5H-thiazol-4-ones 1 and N-itaconimides 2, catalyzed by DP-UAA V (Scheme 1). Firstly, with 1a as the model 5H-thiazol-4

• decreases the free energy of the second formal Mannich reaction, thus improving the reaction rate and chemoselectivity of the [4 + 2] cycloaddition. To extend the usefulness of this reaction, we demonstrate that the adduct can be efficiently reduced with borane. As shown in Scheme 2, 3a was readily reduced

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• , requiring a detailed examination of the kinetic versus thermodynamic effects. The nitroso hetero-Diels–Alder reaction involves the formation of the 3,6-dihydro-2H-1,2-oxazine scaffold 3 from nitroso dienophiles 1 and dienes 2 in a [4 + 2] cycloaddition reaction (Scheme 1). The first nitroso hetero-Diels

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• the Michael products [19] which are the dominant products in polar solvents [25]. Previous mechanistic studies by Koerner and Rickborn [25] have collected strong arguments for a fast concerted [4 + 2]-cycloaddition of the deprotonated anthrone. Michael products were shown to be secondary products of 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

• analogous acetylation–elimination process was experimentally confirmed for quartromicin D1 (151) biosynthesis (Scheme 22) [145]. VstJ has been identified as a probable candidate for the enzyme-catalysed [4 + 2] cycloaddition in versipelostatin A (153) biosynthesis by heterologous expression, gene knockout

• the fact that four [4 + 2] cycloaddition events need to take place to assemble the four monomers into the highly symmetrical natural product [147]. Thiotetronates. Recently, Leadlay et al. presented their findings on the biosynthesis of thiotetronate antibiotics (Scheme 24) [148]. These small

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• , dehydropiperidine or piperidine is consistent with a [4 + 2] cycloaddition across two dehydrated serine residues [79][80]. Genetic disruption of tclM from the thiocillin pathway showed that TclM was responsible for this transformation [81], although the precise cyclisation mechanism (concerted or stepwise) could

(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