Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• [39][40], consisting of a [2 + 2 + 1] cycloaddition between an olefin, alkyne, and carbon monoxide. This reaction has been also applied in cascade approaches [41], and in combination with RCM [42], Diels–Alder [43] and Staudinger [44] reactions to produce novel structurally complex chemical entities

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• analogy to nature’s biosynthetic strategies outlined above, cationic, Diels–Alder, oxidative, and radical cyclization strategies have been successfully applied in total syntheses of terpenoids [53]. In addition, chemists are currently creatively exploring means to mimic classical terpene cyclases and

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• ]. Following this invention, many derivatives were produced to find new viable targets. These studies mostly focused on Diels–Alder cycloadditions to create structures that resemble terpenoids readily available from easily accessible and affordable starting materials like myrcene (1). One of the newly found

• ) (Scheme 3) [17][18][19][20][21]. To produce Ambrelux (32), myrcene (1) is reacted with dienophile (31) in a Diels–Alder cycloaddition promoted under Lewis-acidic conditions. In order to obtain Iso E Super® (33), Brønstedt acid-mediated cyclisation, similar to the one utilised for the first synthesis of

• conditions for the synthesis of all Iso E Super® related compounds vary slightly. The main difference lies in a prolonged isomerisation process of the Diels–Alder product 32 before and after the second cyclisation step. Georgywood® (35) named after Georg Fráter is industrially produced with, e.g., methanol

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• both secondary allylic alcohols and afforded 2 in good overall yield (Scheme 3). Bisacremine E (7) was proposed to be formed in nature via [4 + 2] cycloaddition involving two acremine F (5) units [4]. Although dimerization of 5 through a Diels–Alder cycloaddition is not electronically favorable, we

• undergo Diels–Alder reactions with electron-rich dienophiles [13][14][15][16][17], treatment of 5 with Fukuzumi’s catalyst [18] under illumination with blue light only led to decomposition of the starting material (Table 1, entry 15). Notably, a photoredox catalyst with a lower oxidation potential could

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• Diels–Alder transition state, whilst those which were electron-withdrawing (e.g., NO2, CN, NMeAc) decreased the reaction rate. Interestingly, strong EDG (e.g., OMe, NMe2) exhibited a slower reaction rate than predicted, but this is likely due to the increased stabilisation of the reactant, rather than

• spectroscopically at −20 °C [4]. There have been numerous reports of pentafulvenes undergoing dimerization via Diels–Alder cycloadditions (DACs) (Scheme 8) at room temperature [6][66][108][109][114][115][117][119]. In some cases, the resulting dimers can undergo subsequent cycloadditions to form trimers via [6 + 4

• , when the fulvene has an EWG attached, it is more likely to function as a dienophile in an inverse electron-demand Diels–Alder (iEDDA) reaction [153][154][156]. This requires the other reactant to have strong EDGs in order to function as a diene, otherwise fulvene dimerization becomes the preferred

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

• Kenta Tanaka,
• Yuta Tanaka,
• Mami Kishimoto,
• Yujiro Hoshino and
• Kiyoshi Honda

Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208

• green light irradiation [24][25]. In the course of this study, we found that these thioxanthylium photocatalysts efficiently oxidized styrene derivatives such as trans-anethole, and promoted radical cation Diels–Alder reactions. Based on the background mentioned above, in order to expand the utility of

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• reaction and as organocatalysts in Diels–Alder reactions [27]. The group of Metrangolo also reported halogen bonding-promoted catalysis in water by exploiting a halogen bonding amino acid, which combines excellent donor properties with good water solubility [28], in addition to their seminal contributions

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• reviewed in this article. Syntheses were clustered based on: i) syntheses using tetralone (Figure 2, route A nad B), ʟ-abietic acid and/or ʟ-dehydroabietic acid as starting materials (route C, D and E); ii) syntheses using Diels–Alder reactions for the construction the A, B and C-rings (route F and G); iii

• -elimination and acid hydrolysis to give the key triptophenolide methyl ether (8) in racemic form (16.5%). In 2008, Sherburn and co-workers developed an approach to the formal synthesis of triptolide (Figure 2, route G, Scheme 5) [71]. Key features of the synthesis include two intermolecular Diels–Alder

• reactions and a newly developed deoxygenative aromatization procedure. The first enantioselective Diels–Alder reaction, which is an intermolecular cycloaddition and lactonization between (Z)-3-iodo-4-methylpenta-2,4-dien-1-ol (29) and methyl acrylate (30) in the presence of Mikami’s (binol)TiCl2 catalyst to

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