Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• separation. This problem was resolved by the introduction of scandium triflate (Sc(OTf)3) as a promising reusable Lewis acid in Diels–Alder reactions by Kobayashi [78]. However, in recent years scandium(III) trifluoromethanesulfonate (Sc(OTf)3) has emerged as an efficient, mild, commercially available

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• mixture of 19 and 18 (3:2 ratio), accompanied with a small amount of 22. As a substitute for dianthracene 19, thermally more stable substrate, anthracene-N-methyl maleimide adduct 25 [54] was prepared by Diels–Alder reaction under high pressure conditions as well as by microwave-assisted reaction and

Enantioselective Diels–Alder reaction of anthracene by chiral tritylium catalysis

• Qichao Zhang,
• Jian Lv and
• Sanzhong Luo

Beilstein J. Org. Chem. 2019, 15, 1304–1312, doi:10.3762/bjoc.15.129

• of a highly active carbocation Lewis acid catalyst. The stereocontrol potential of the chiral tritylium ion pair was demonstrated by its application in an enantioselective Diels–Alder reaction of anthracene. Keywords: anthracene; carbocation catalysis; Diels–Alder reaction; Fe(III)-based phosphate

• presence of strong Lewis acids [36]. We herein report the design and exploration of a new trityl carbocation that has a chiral weakly coordinating Fe(III)-based phosphate anion for the effective asymmetric catalysis in the Diels–Alder reaction of anthracenes. Results and Discussion In our previous work, we

• ; see Supporting Information File 1 for details). We next tested the metal phosphate strategy in the Diels–Alder reaction of anthracene, for which a catalytic asymmetric version has not been achieved yet. Recently, we reported that the tritylium salt [Ph3C][BArF], in situ generated by Ph3CBr and NaBArF

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• , which allows to obtain chiral cyclic sulfones with high enantioselectivity [10][11][12]. Also non-racemic cyclic sulfones can be obtained by the Diels–Alder reaction, catalyzed by chiral Lewis acids or organocatalysts. Rh- and Cu-catalyzed CH-insertion reactions occurring at moderate or high

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• presence of I2 as catalyst. The mechanism follows the initial formation of the imine compound between the aldehyde and the arylamine, followed by an imino-Diels–Alder reaction with the enolate generated from the ketosteroid. The reaction is highly regioselective for the enolization of the ketone, thus

• nitrogen atom in their nucleus) [53][54]. This strategy employs domino Knoevenagel/hetero-Diels–Alder procedures for the assembly of such steroid mimics. However, we have decided not to include it in this review because several book chapters and reviews have already covered this chemistry [55][56]. 4

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• atmosphere to relative degrees depending on equipment [5][26][27][28][29][30][31][32][33][34]. In particular, the Mack group has used an elegant strategy to evaluate the energy delivery for a Diels–Alder reaction performed under mechanochemical conditions and was able to correlate reactivity, or lack thereof

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• -supported catalysts amenable for continuous-flow asymmetric enamine catalysis [9][10]. The acid-catalyzed polymerization of furfuryl alcohol renders a dark polymer featuring a complex cross-linked polyunsaturated scaffold derived from polycondensation and Diels–Alder reactions [11][12]. Worldwide, there is

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• be protected as a cyclic acetal instead of the more labile acyclic acetal [5][6]. The maleimide group was incorporated into ODNs as a Diels–Alder adduct with dimethylfuran. Besides the need of an additional step for deprotection, only examples of 5'-end modification was given probably due to the

Switchable selectivity in Pd-catalyzed [3 + 2] annulations of γ-oxy-2-cycloalkenones with 3-oxoglutarates: C–C/C–C vs C–C/O–C bond formation

• Yang Liu,
• Julie Oble and
• Giovanni Poli

Beilstein J. Org. Chem. 2019, 15, 1107–1115, doi:10.3762/bjoc.15.107

• cyclopentenone 4-benzoate (2b) under conditions A did not allow the formation of the corresponding C–C/O–C annulated product. Instead, elimination of the benzoate anion, very likely from the transiently formed η3-allylpalladium complex, gave cyclopentadienone, which underwent the known self-Diels–Alder

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• analogues of these compounds by a sequential Ugi/Diels–Alder approach and, in this context, they were able to separate the enantiomers using chiral chromatography. Some of these compounds showed good in vitro potency blocking the cardiac ion channel Kv1.5 and, therefore, are promising agents to treat atrial

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• illudine [11], aromadendrane [12], marasmene [13] and fomannosane [14] type skeletons. Although bovistol could formally be supposed to be a triterpene, it is thought to be derived by a hetero-Diels–Alder reaction of two sesquiterpenes to form a dimeric sesquiterpenoid [15]. In the recently published genome

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• formation of a supramolecular structure whereas that of 6, containing additional CF3 substituents, shows the formation of a monomeric structure. Diols 1–6 were found to be active organocatalysts in oxo-Diels–Alder reactions in which 2 recorded a 72% ee with trimethylacetaldehyde as a substrate. Keywords

• : asymmetric organocatalysis; axial chirality; biaryls; hydrogen bond; oxo-Diels–Alder reaction; Introduction The Diels–Alder (DA) reaction is a useful and easy-to-perform method for the synthesis of six-membered rings through the direct formation of C–C bonds between a diene and a dienophile (a substituted

• alkene); it is called a hetero-Diels–Alder (HDA) reaction when one or more heteroatoms (most often oxygen or nitrogen) are present among the reactants, such as the use of carbonyl compounds or imines as dienophiles [1][2][3][4][5]. An asymmetric HDA reaction is capable of introducing up to four

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• applied a Diels–Alder reaction of 1,2,4,5-tetrazine with a terminal alkyne unit in a 21-crown-7-based [2]pseudorotaxane 14. The [2]rotaxane 15 was produced in 81% yield having pyridazine groups as stoppers (Figure 7). Very recently, Nierengarten and co-workers reported a solvent-free mechanochemical

Coordination chemistry and photoswitching of dinuclear macrocyclic cadmium-, nickel-, and zinc complexes containing azobenzene carboxylato co-ligands

• Jennifer Klose,
• Tobias Severin,
• Peter Hahn,
• Alexander Jeremies,
• Jens Bergmann,
• Daniel Fuhrmann,
• Jan Griebel,
• Bernd Abel and
• Berthold Kersting

Beilstein J. Org. Chem. 2019, 15, 840–851, doi:10.3762/bjoc.15.81

• drastically alter its structural properties and reactivities. Prominent examples are the cis-bromination of α,β-unsaturated carboxylato ligands [2], regioselective Diels–Alder reactions of encapsulated dienoate ligands [3], and the stabilization of unusual co-ligand conformations, respectively [4]. The

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• -methoxy-ortho-xylene in only 5% yield [14]. 4-HO-OPA was also described in 1997 by Taylor et al. as a crude product (via a Diels–Alder reaction of commercially available Danishefsky diene with 4,4-diethoxybut-2-ynal) for the synthesis of an antitumor analogue [15]. This aforementioned strategy was applied

• (MAOS) protocol for 2 was also tested in a basic medium with tetrabutylammonium bromide [18]. Nevertheless, this convenient time-saving procedure (15 minutes) shows a lower 74% yield due to the presence of a byproduct (propargylic alcohol) as evidenced by NMR spectroscopy. An intramolecular Diels–Alder

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• glycoengineering (MGE). They readily react with tetrazines in an inverse electron-demand Diels–Alder (DAinv) reaction, a prime example of a bioorthogonal ligation reaction, allowing their visualization in biological systems. Here, we present a comparative study of six cyclopropene-modified hexosamine derivatives

• Diels–Alder reaction; metabolic engineering; Introduction Carbohydrates are an important class of biological molecules involved in many fundamental biological processes [1]. An important tool to visualize glycoconjugates in vitro and in vivo is metabolic glycoengineering (MGE) [2][3][4]. In this

• can be ligated through the inverse electron-demand Diels–Alder (DAinv) reaction with 1,2,4,5-tetrazines [13][14][15][16][17]. This reaction is advantageous since it is fast, irreversible, and does not require a toxic heavy metal catalyst. Different terminal alkenes that are connected to sugars by an

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• not show any toxicity against L6 cells (a primary cell line derived from rat skeletal myoblasts). These results contribute to a better understanding of artemisinins mechanism of action. Keywords: artemisinin; biomimetic synthesis; Diels–Alder reaction; malaria; peroxides; Introduction The isolation

• the propargylic moiety with Red-Al. BAIB/TEMPO oxidation of this alcohol gave ketone 7. By a Reformatsky reaction of 7 using Zn/ethyl bromoacetate derivative 8 was obtained, which was subjected to a thermal (190 °C, toluene) intramolecular Diels–Alder reaction resulting in the formation of the β

• prove this hypothesis. Experimental Experimental details, NMR spectra and other physical data are shown in Supporting Information File 1. Structures of the natural (+)-artemisinin (1) and the synthesized (+)-3-hydroxymethylartemisinin (2). Synthesis of the Diels–Alder precursor 8 over four steps in 71

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• Diels–Alder [43], Asinger–Ugi [44], etc. Another class of reactions highlight the importance of the distinct kinetic reactivity of similar FGs present in the reactants and in the initial adducts of the first transformation, then enabling productive and selective combinations of the MCRs. The synthesis

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• palladium-catalyzed reaction that results in phenanthrene derivatives using aryl iodides, ortho-bromobenzoyl chlorides and norbornadiene in one pot. This dramatic transformation undergoes ortho-C–H activation, decarbonylation and subsequent a retro-Diels–Alder process. Pleasantly, this protocol has a wider

• compound z-6 was isolated in 88% yield. Based on the above experimental results and the use of norbornadiene in Catellani reactions followed by retro-Diels–Alder reaction firstly reported by Lautens et al. [22][23][24], which is mentioned in recent works [11], a proposed mechanism for this domino reaction

• , G will experience immediate retro-Diels–Alder reaction after the catalytic cycle to afford the target product while taking off cyclopentadiene. Conclusion In summary, we have developed a novel and efficient protocol which allows us to construct a variety of phenanthrene derivatives starting from

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• tert-butyl ester function and finally hydrogenolytic opening of the isoxazolidine ring with simultaneous protection of the amino group (Scheme 18). By Diels–Alder reaction Acylnitroso derivative 74 prepared from methyl N-Boc-L-alaninate underwent Diels–Alder reaction with cyclopentadiene to produce

• [86][87][88] or a Diels–Alder reaction using acylnitroso compounds [89]. However, when compared with these multistep approaches hydroxylation of pyroglutamic acid derivatives seems to be the simplest option. Treatment of the lithium enolate of benzyl N-Boc-pyroglutamate (S)-86 with Davis oxaziridine

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• -substituted tetrazines via a Diels–Alder reaction with inverse electron demand has been studied with NMR and with electrospray ionization mass spectrometry. A catalytic cycle with three intermediates has been proposed. An enamine derived from L-proline and acetone acts as an electron-rich dienophile in a [4

• + 2] cycloaddition with the electron-poor tetrazine forming a tetraazabicyclo[2.2.2]octadiene derivative which then eliminates N2 in a retro-Diels–Alder reaction to yield a 4,5-dihydropyridazine species. The reaction was studied in three variants: unmodified, with a charge-tagged substrate, and with a

• intermediates [4][5][6]. Various types of reactions have been studied successfully by ESIMS ranging from Ziegler–Natta polymerization [7] and coupling reactions [8][9] to organic reactions such as the Baylis–Hillman [10][11][12][13][14][15], aldol [16][17][18] or Diels–Alder reactions [19][20]. An advantageous

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• [50]. Further mutations within the cavity of NB provide a hydrophobic cavity. Several studies reported on the utilization of NB as scaffold for incorporated metal complexes, including the work of Hayashi et al. capitalizing on the polymerization of phenylacetylene [50][51], the Diels–Alder reaction

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• functional group and the substrate structure and may follow a different reaction course than what is usually observed. In cases where ROM–RCEYM occurred, the resulting 1,3-diene reacts in situ with the dienophile to provide condensed tetracyclic systems. Keywords: Diels–Alder reaction; domino process; enyne

• ] of norbornene derivatives with a suitably located alkynyl side-chain on the nucleus (path 2, Scheme 1) to form carbocycles has been less explored. The greatest advantage of this protocol lies in its potential in increasing the molecular complexity through Diels–Alder reaction of the resulting ring

• system. Domino metathesis of oxa- and aza-norbornenes with alkyne side chains [38][39][40] as well as norbornene derivatives having ether linked alkynes [41][42] in combination with Diels–Alder reaction of the resulting 1,3-dienes have been investigated to construct polycycles with heteroatoms. In spite

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• reactions [27] to achieve cis-hydrindan-2,4-diones, their application to rapidly assemble the five-membered ring of the targeted 6,5-bicylic system has not been reported until now. Two examples using cycloaddition processes in this field should be mentioned: Diels–Alder [28] and Pauson–Khand [29] reactions

Design and synthesis of C₃-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

• Sambasivarao Kotha,
• Saidulu Todeti and
• Vikas R. Aswar

Beilstein J. Org. Chem. 2018, 14, 2537–2544, doi:10.3762/bjoc.14.230

• groups and a benzene ring as a central core. The synthesis of these C3-symmetric molecules involves simple starting materials. Our approach to C3-symmetric compounds relies on a Diels–Alder reaction, cyclotrimerization and ring-closing metathesis as key steps. Keywords: cyclotrimerization; Diels–Alder

• (−)-aspidophytine (5) differs from 1-acetylaspidoalbidine (4) only in the degree of unsaturation and the substitution pattern on the aromatic ring (Figure 1). The design of propellanes demands unique synthetic methods and these include: manganese or palladium-catalyzed transformations [10], the Diels–Alder (DA