New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• atoms covalently bonded to a benzylic carbon (Scheme 8). In 2016 Maruoka and Shirakawa followed up the aforementioned studies by demonstrating that tetraalkylammonium salts L5, L6, L11 and L12 as well as TBAI could activate imines toward aza-Diels–Alder reaction with Danishefsky’s diene (Scheme 9) [51

• coordinating TfO− anion did not accelerate the cycloaddition. In 2015, Takeda, Minakata and co-workers demonstrated that 2-iodoimidazolium salt L24 could serve as an efficient catalyst of the aza-Diels−Alder reaction of aldimines and Danishefsky diene (Scheme 19) [90]. Other organohalides such as

• bond-donor catalysts by Bibal and co-workers [53][54]. Tetraalkylammonium catalyst (L6)-catalyzed dearomatization of isoquinolinium salts [50]. Tetraalkylammonium catalyst L6 complexation to halogen-containing substrates [51]. Tetraalkylammonium-catalyzed aza-Diels–Alder reaction by Maruoka and co

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• -decalins and trans-hydrindanes (Scheme 1) [22][23][24][25]. It relies on the use of sugar-derived allyltin (such as 5) followed by ZnCl2-induced fragmentation into dienoaldehyde 6, subsequent Horner–Wadsworth–Emmons olefination, and intramolecular Diels–Alder reaction. In this paper, we explore the

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• donating (“pushing”) oxygen atom. Monomers with such substitution patterns are defined as captodative or push–pull monomers [1]. MLA was first synthesized in 1969 by Scheibelhoffer et al. through a bromination of L-lactide followed by a basic HBr elimination [2]. In 2008, the first Diels–Alder reaction

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• reaction, resulting in a highly selective catalyst for the cycloaddition reaction. Keywords: catalysis; Diels–Alder; retro-Diels–Alder; zeolites; Introduction The Diels–Alder reaction (DAR) is one of the most useful reactions in organic synthesis. In order to improve the yield and to avoid the

• ] in where different stereoisomers could be obtained. Lewis-acid centers contained within the framework of zeolite beta (Zr-β, Sn-β) are useful catalysts in the Diels–Alder reaction for the production of bio-based terephthalic acid precursors, one of the monomers for the synthesis of polyethylene

• Diels–Alder reaction selectivity [28]. The DAR of cyclopentadiene with p-benzoquinone is a well-known example of cycloadditions, and some results can be found on the control of the selectivity to the different isomers. In homogeneous phase, equimolar amounts of diene and dienophile afford two isomers

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• obtained via an intramolecular Diels–Alder reaction, epoxidation and protection (Scheme 22) [170]. Conclusion The direct oxidative cyclization of 1,5-dienes is known for more than 90 years, since the early finding by Kötz and Steche in 1924. While mechanistic and stereochemical aspects were in the center

Diastereoselective synthesis of 3,4-dihydro-2H-pyran-4-carboxamides through an unusual regiospecific quasi-hydrolysis of a cyano group

• Mikhail Yu. Ievlev,
• Oleg V. Ershov,
• Mikhail Yu. Belikov,
• Angelina G. Milovidova,
• Viktor A. Tafeenko and
• Oleg E. Nasakin

Beilstein J. Org. Chem. 2016, 12, 2093–2098, doi:10.3762/bjoc.12.198

• been recently described is the involvement of diazolactones in an inverse electron-demand Diels–Alder reaction [13]. At the same time the synthesis of 3,4-dihydro-2H-pyrans with a carboxamide group is a not sufficiently explored area. There is only one way to produce 3,4-dihydro-2H-pyran-4-carboxamides

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

• , Czech Republic Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA 10.3762/bjoc.12.184 Abstract The hetero-Diels–Alder reaction between a nitroso dienophile and a conjugated diene to give the 3,6-dihydro-2H-1,2-oxazine scaffold is useful for the synthesis of

• stereo- and regioselectivity for the synthesis of 1,2-oxazine scaffolds. Keywords: diene; hetero-Diels–Alder; nitroso compounds; regioselectivity; stereoselectivity; Review Introduction The hetero-Diels–Alder reaction represents one of the most important methods in organic synthesis, providing various

• biologically active compounds. It is a variant of the Diels–Alder reaction where either the diene or the dienophile contains a heteroatom. Hetero-Diels–Alder reactions between conjugated dienes and nitroso dienophiles affording 1,2-oxazines are utilized for the synthesis of many biologically active molecules

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• reported the synthesis of a novel chiral auxiliary that demonstrated to be very efficient in an asymmetric Diels–Alder reaction between the acrylic ester derivative and cyclopentadiene [16]. The facial selectivity of this reaction proved to be due to an aryl–vinyl π-stacking intramolecular interaction that

• room temperature, account for this explanation. With the aim to determine if the strength of the intramolecular π-stacking interaction can have any influence in the inductive capacity, we studied the Diels–Alder reaction of acrylates 6a,b with cyclopentadiene (Table 2). All cycloadditions were endo

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• ions produced via retro-Diels–Alder reaction [5][6]. Such diagnostic fragment ions are of high value to delineate structural proposals for unknown analytes from their mass spectra, but for unambiguous proof of the suggested structures a synthesis of reference material is essential. Back in the 1960s

Artificial Diels–Alderase based on the transmembrane protein FhuA

• Hassan Osseili,
• Daniel F. Sauer,
• Klaus Beckerle,
• Marcus Arlt,
• Tomoki Himiyama,
• Tino Polen,
• Akira Onoda,
• Ulrich Schwaneberg,
• Takashi Hayashi and
• Jun Okuda

Beilstein J. Org. Chem. 2016, 12, 1314–1321, doi:10.3762/bjoc.12.124

• . Copper(II) was attached by coordination to a terpyridyl ligand. The spacer length was varied in the back of the ligand framework. These biohybrid catalysts were shown to be active in the Diels–Alder reaction of a chalcone derivative with cyclopentadiene to preferentially give the endo product. Keywords

• reported. The Diels–Alder reaction is a powerful C–C bond formation reaction, widely used in organic chemistry, e.g., for the synthesis of natural products [28]. This reaction is known to be catalyzed by Lewis acids such as a Cu(II) complex [29]. Additionally, structurally defined catalysts are found to

• = 6301 Da). The signal of m/z = 6111 Da results from saponification of the ester and the maleimide moiety (calcd (M + H2O + Na+): m/z = 6111 Da, found: m/z = 6111 Da). We were unable to detect the copper ion in the MALDI–TOF–MS. The isolated biohybrid catalysts were tested in the Diels–Alder reaction of

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• Diels–Alder reaction as the late stage key step. After extensive purification, the authors were able to isolate keramaphidin B in just 0.3% yield, but nevertheless they provided evidence for the biosynthesis [3]. A year later, Baldwin et al. completed an alternative synthesis by performing an

• intermolecular Diels–Alder reaction and a double late stage RCM reaction to close the two macrocyclic rings; albeit the last stage afforded 1 in 1% yield after separation of various oligomeric byproducts [4]. Our group has had a long-standing research program dedicated towards the total syntheses of the

The synthesis of functionalized bridged polycycles via C–H bond insertion

• Jiun-Le Shih,
• Po-An Chen and
• Jeremy A. May

Beilstein J. Org. Chem. 2016, 12, 985–999, doi:10.3762/bjoc.12.97

• alternative positions, or the synthetic strategy must be completely altered as the original method is not capable of synthesizing other isomers. For example, multiple research groups have shown that the bridged bicyclo[2.2.2]octane core 1 of maoecrystal V may be constructed via an intramolecular Diels–Alder

• reaction from a functionalized 1,3-diene like 2 (Figure 2) [13][14][15][16]. However, such a reaction would not be applicable to synthesize the bicyclo[3.2.1]octane core 3 of taxuspine C, as the mechanistic requirements in a Diels–Alder cycloaddition are not met with a 1,4-diene. Strategies that may access

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• two other examples (Scheme 7b), however, rhodanines of type 45 have been employed to produce spirocyclic compounds. The first case is an enamine/Michael tandem reaction to unsaturated enones [81] (Scheme 7b,1) and the second one is the Diels–Alder reaction with 2,4-dienals which occurs via trienamine

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• -fused pyran-3-ones and the results are reported herein. Results and Discussion For a long time, the Diels–Alder reaction of simple heterosubstituted 1,3-dienes has been considered a standard procedure to prepare highly functionalized ring systems [28]. Taking advantage of diazalactones to act as the

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• hydroxy group) exhibited poor enantioselectivity. These effects may suggest and support the bifunctional role played by the catalyst (Figure 8). Diels–Alder reaction An important contribution in the construction of highly substituted carbocyclic compounds was disclosed by Tan’s group in 2009. In this work

• . Diels–Alder reaction catalyzed by the aminoindanol derivative ent-41. Asymmetric Michael addition of 3-pentanone (55a) to the nitroalkenes 3 through aminocatalysis. Substrate scope extension for the asymmetric Michael addition between the ketones 55 and the nitroalkenes 3 through aminocatalysis. A

(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

• a variety of transformations. Utilizing the primary amine-thiourea 18, an enantioselective formal aza-Diels–Alder reaction of enones 12 and 13 was reported. In this reaction the enamine is formed from the side of the methyl ketone, which is conjugated with the pre-existing double bond, providing the

• electron-rich diene, which reacts with substituted dihydroisoquinoline 14 and dihydro-β-carboline 15, so that cyclohexanone derivatives 16 and 17 will be produced, respectively (Scheme 8) [19]. Also, a cyclic derivative of 13 was utilized (not shown). This aza-Diels–Alder reaction provides products with

• , the product was obtained in 78–90% yield and 15–92% ee. Finally, β-substituted α,β-unsaturated aldehydes were completely unreactive. In 2012, a proposed inverse electron-demand Diels–Alder reaction was reported by Wang and co-workers, obtaining enantiopure products 33, starting from diene 31 and

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• Melchiorre. A Diels–Alder reaction of indole-2,3-quinodimethane 76 (generated from 77 and the prolinol catalyst 78 ) with the enone 79 affords a tetrahydrocarbazole derivative 80. The NHC precatalyst 22 then promotes an intramolecular cross-benzoin condensation of the keto-aldehyde to furnish the tetracyclic

• cycloadducts 84 in good yield and enantioselectivity [63]. Initially, the trienamine 85 is generated by the action of prolinol catalyst 86 on the dienal 82. The former (85) then undergoes a Diels–Alder reaction with the sulfonylimine 83 to generate the keto-aldehyde 87. Finally, the NHC precatalyst 22 mediates

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• isoindolinones have been developed. The first method was the synthesis of 3-substituted isoindolinones from the corresponding N-methylmaleimides by the Diels–Alder reaction with 1,3-butadiene followed by hydrogenation. The second and the third methods employed the corresponding dicarboxylic acids and the

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• –Alder reaction at higher temperatures, causing a mass loss during polymerization if higher temperatures are applied for the reaction. To test the pre-catalysts regarding their performance in the polymerization of DCPD, two different test-reactions were carried out: a) STA measurements to gain an insight

• polymerization of DCPD is their outstanding solubility in the neat monomer. The main challenge of the polymerization of DCPD is to guarantee an adequate mixing of monomer and catalyst to obtain a homogenous reaction mixture and moreover a steady polymerization product. DCPD is also prone to undergo a retro-Diels

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

• : dearomatization; decarboxylation; Diels–Alder reaction; oxidation; pentafluorosulfanyl group; Introduction Fluorinated organic compounds have been one of the foci of chemical industry for the last several decades. The unique properties of fluorine atoms and fluorinated groups have been exploited in various

• oxidation of aromatics. Benzoquinone 12 is a solid material with good stability at −20 °C. Several standard reactions were investigated. Reduction to hydroquinone 15 using catalytic palladium was very efficient (Scheme 5). The Diels–Alder reaction with cyclopentadiene proceeded in a high yield at ambient

• acid 4, some basic chemical reactivity studies were performed. When heated to about 125 °C under reduced pressure, acid 4 eliminated water to afford anhydride 20 in a good yield. Anhydride 20 underwent a Diels–Alder reaction with cyclopentadiene at ambient temperature to provide a mixture of endo and

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• ][24][25][26]. Several new developments in the related hetero-Diels–Alder reaction of acylnitroso species have also been reported recently [27][28][29][30]. These methodologies generally involve in situ generation of the acylnitroso species, achieved using a variety of oxidants including vanadium- [28

• trapped by hetero-Diels–Alder reaction with dienes [54][55], and detection of the resulting hetero-Diels–Alder adducts used to confirm the formation of free nitroso intermediates. Thus trapping experiments were conducted using isoprene (14) to investigate the formation of a nitroso species in this

• reaction. First a 1:1 mixture of cycloadducts 15 and 16 was synthesised as a reference sample using Kirby’s conditions for the hetero-Diels–Alder reaction (N-Boc-hydroxylamine (8), isoprene (14) and sodium periodate, Scheme 3a) [54][55]. Then isoprene (14) and N-Boc-hydroxylamine (8) were combined in

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• ester 75. Finally, an elegant cascade reaction involving an aldol condensation, followed by a hetereo Diels–Alder reaction closed the last three rings and antheliolide A (18) was obtained in 74% yield. In summary, the successful total synthesis of antheliolide A proceeded in 25 linear steps with an

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• group. The energy barrier of a distorted benzene ring would then be compensated by rearomatization in 23 after intramolecular Diels–Alder reaction. This mechanism would involve a 1,2-hydride shift and a nucleophilic attack of water at C-2’. The second discussed route starts with a nucleophilic attack of

• the phenolic oxygen at C-6 to close the macrocycle in 25. In this mechanism, the aromaticity of the phenol ring remains untouched. Intramolecular Diels–Alder reaction gives rise to the hexacyclic system 26, which would then be oxidized to pyrrocidine A (24) at C-2’. In contrast to route A, the

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

• yields, referred to the starting compounds 3/3', are reported in Scheme 2. No epimerisation reactions occurred during the hydrolytic processes as demonstrated via 2D NMR experiments (COSY, HSQC). Discussion In the Diels–Alder reaction of vinylindoles 1 with methyl 2-acetamidoacrylate (2), among tested

• and 4). It is well known that reaction rates and selectivity in Diels–Alder reactions are affected by solvents [30][31][32]. In particular, polarity and hydrogen bond donor ability of the solvent can impact the diastereoisomeric ratios in a Diels–Alder reaction. Such an effect seems negligible in the

Stereochemistry of ring-opening/cross metathesis reactions of exo- and endo-7-oxabicyclo[2.2.1]hept-5-ene-2-carbonitriles with allyl alcohol and allyl acetate

• Piotr Wałejko,
• Michał Dąbrowski,
• Lech Szczepaniak,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 1893–1901, doi:10.3762/bjoc.11.204

• reaction may be improved by using neat reaction conditions. Experimental A mixture of 1 and 2 (1.6:1) is readily available from the Diels–Alder reaction of furan and acrylonitrile according to the literature procedure [28][29]. The pure isomers were isolated by column chromatography. The 1H and 13C NMR