Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• abstracted, resulting in d8-α-cubebene [M]+• with m/z = 212 as highly labeled isotopologue (Figure 4, lower mass spectrum). Biosynthesis of sesquiterpene hydrocarbons via (R)-(+)-germacrene D Lodewyk, Gutta and Tantillo postulated an α-ylangene-forming carbocation cascade based on computer calculations [34

Inherent atomic mobility changes in carbocation intermediates during the sesterterpene cyclization cascade

• Hajime Sato,
• Takaaki Mitsuhashi,
• Mami Yamazaki,
• Ikuro Abe and
• Masanobu Uchiyama

Beilstein J. Org. Chem. 2019, 15, 1890–1897, doi:10.3762/bjoc.15.184

• the first detailed analysis of the inherent atomic mobility in carbocation intermediates during sesterterpene biosynthesis. We identified two methyl groups as the least mobile of all the carbons of the carbocation intermediates in the first half of the cyclization cascade. Our analysis suggests that

• ) triggering the biosynthetic cyclization cascade by the elimination of pyrophosphate or by protonation; (ii) preorganization of the substrate to generate the reactive conformation; (iii) protection of reactive intermediates from water; and (iv) termination of the reaction by deprotonation or hydration. We

• previously established the importance of conformation in the carbocation cyclization cascade [1], focusing on two sesterterpenes, i.e., quiannulatene [1][2] and sesterfisherol [3][4][5], as representative examples. These two sesterterpenes are synthesized via a 5/12/5 tricyclic intermediate, which leads to a

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• together with 1.5 equivalents of 3a led to a higher conversion (ca. 90%), affording acceptable yield and selectivity (Table 1, entry 5). With optimized reaction conditions in hand (Table 1, entry 5), we then examined the generality of this four-component radical cascade reaction using xanthates 1, olefins

• functionalized keto-aldehydes [22], aminoalcohols [30], triazoles [31], just to name a few. A reaction mechanism is finally proposed for the four-component cascade reaction, which is depicted in Figure 2 [22][23][24][32][33][34]. Initially, α-carbonyl radical A [8] was generated by the reaction of the

• radical which sustains the radical chain. Since radical B can also add to sulfonyl oxime ether 3a, we used high CO pressure conditions to encourage the radical carbonylation to form acyl radical C. Conclusion In summary, we demonstrated that a four-component radical cascade reaction, between xanthogenates

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• a trans relationship between the C4 and C5 substituents [13][14][15]. It is believed that the 4π conrotatory electrocyclization step that converts the pentadienyl cation 5 into the corresponding cyclopentenone adduct 6 is responsible for controlling the relative diastereoselectivity in this cascade

• furan ring required to initiate the cascade sequence. This highlights that a balance between nucleophilicity and hydrogen bond capabilities are required to obtain an efficient and selective reaction. Compared to the rearrangement of furylcarbinol 1a, sterically bulky aryl groups attached to the

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• been developed between isocyanides, sulfur and alcohols or thiols under mild reaction conditions to afford O-thiocarbamates and dithiocarbamates in moderate to good yields. The one-pot reaction cascade involves the formation of an isothiocyanate intermediate, thus a catalyst-free synthesis of

• functional group tolerance to halogen, olefin and nitrile groups among others. Moreover, this multicomponent reaction is suitable for a one-pot cascade annulation providing a thioxo dihydroquinazolinone derivative in a metal-free approach. Compared to other reported syntheses of thiocarbamates, this method

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• nanoreactor which is a single molecule as catalyst in the earliest steps of the mechanistic pathway (Figure 6). This multicomponent reaction is expected to comprise a series of condensations and subsequent ring-closure cascade reactions (Scheme 3). To demonstrate the mechanistic pathway, dimedone (2), isatin

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• -coupling reactions. Herein, stereodefined 1,3-enynes, including tetrasubstituted ones, were straightforwardly synthesized from cis or trans-alkynylated oxiranes in good to excellent yields by a one-pot cascade process. The procedure relies on oxirane deprotonation, borylation and a stereospecific

• -enynes through lithiation, borylation and rearrangement of cis or trans-alkynyloxiranes. This cascade reaction is stereospecific, probably due to the stereocontrolled group transfer from boron to the adjacent oxiranyl carbon in an oxiranylborate complex intermediate, followed by an internal bora-Wittig

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

• stepwise Pd(II)-catalyzed cascade process or a [4 + 2] cycloaddition reaction, both providing the cis stereochemistry at C-2 and C-3. When the reaction was carried out with the epimer of substrate 33 (having the 5β-hydroxy group), the cis stereochemistry was also achieved at the newly formed C-2 and C-3

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• ionisation of the substrate FPP and the formation of a humulyl cation as an intermediate in the biosynthesis of pentalenene [45][46][48][49], while the later steps of the cyclisation cascade were subject to revision based on the findings of quantum chemical calculations [50][51]. The α-amorphene synthase

• -MIB (2). First, GPP is methylated to 14 by a SAM-dependent methyltransferase, followed by a terpene synthase catalysed cyclisation through a cationic cascade to 2. Oxidation products derived from 3 by the cytochrome P450 monooxygenase that is genetically clustered with the epi-isozizaene synthase in

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

• cascade – transformations [6][7][8][9][10][11] as well as annulation reactions [12][13][14][15] occupy a special place as they facilitate the synthesis of a variety of complex cycles in a single synthetic operation, through sequential and mechanistically independent bond-forming steps. In the frame of our

• [32]. Furthermore, when the newly formed annulation product contains an ortho-haloaryl moiety at the nitrogen substituent, an additional intramolecular keto α-arylation step can be involved in the cascade, thereby forming two new cycles and three new bonds in the same synthetic operation (Scheme 1

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

• structure. Those starting materials must be added all together in the reaction container and, therefore, other approaches [67][68][69] featuring sequential (domino, tandem or cascade) [70][71] reactions, where one intermediate is initially preformed before additional reagents are added, are not included in

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• aminoazole fragments. In all earlier described experiments with participation of different α-aminoazoles as binucleophiles the reaction cascade readily accomplished by the formation of fused heterocyclic systems [25]. An analogous three-component reaction involving indole or imidazo[1,2-a]pyridine

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• or multiple compounds, are terpene synthases (TSs). These enzymes are able to guide complex cascade reactions from structurally simple oligoprenyl diphosphates to often complex, polycyclic products [4][5][6] circumventing the low selectivity observed for carbocationic reactions by a defined active

• be straightforward at first sight, the details proofed to be challenging as deeper insights for the stereochemistry of each step were obtained by incubation experiments. The question, whether (R)-NPP or its enantiomer (S)-NPP is involved in the HcS catalysed cyclisation cascade, was addressed by

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

• provided by the putative sesquiterpene synthase AAE3_04120. Combining these indications, an enzymatic cascade coded by the AAE3_04120 cluster is transforming Δ6-protoilludene into illudine(s) and the corresponding bovistol in C. aegerita (Figure S2, Supporting Information File 1). Further research has to

SO₂F₂-mediated transformation of 2'-hydroxyacetophenones to benzo-oxetes

• Revathi Lekkala,
• Ravindar Lekkala,
• Balakrishna Moku,
• K. P. Rakesh and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 976–980, doi:10.3762/bjoc.15.95

• through a catalyst-free cascade method (Scheme 1c). Results and Discussion Initially, we screened various reaction conditions (see Supporting Information File 1) using 1-(2-hydroxyphenyl)ethanone (1a) as a model substrate. As illustrated in Table 1, the desired product 2a was produced in 50–76% yield when

• protocol for the transformation of 2'-hydroxyacetophenones to benzo-oxetes. This SO2F2-mediated cascade reaction showed exceptional functional group tolerance and a broad substrate scope which, to the best of our knowledge, is the first example of employing cheap and abundant 2'-hydroxyacetophenones as

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

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

• achieved from benzyl alcohol using a Br+ source as the catalyst (Figure 16). In the reaction pot subcomponents such as benzaldehydes and H+ were formed which further participated in a cascade transformation to give dihydropyrimidones 29. Dynamic combinatorial chemistry and mechano-milling Dynamic

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, People’s Republic of China 10.3762/bjoc.15.76 Abstract A diastereoselective approach to axially chiral imidazopyridine-containing biaryls has been developed. The reactions proceed through a radical cyclization cascade to construct

• ] have studied the reactions of electrochemically generated NCRs. Particularly, we have recently reported an electrochemical synthesis of imidazo-fused N-heteroaromatic compounds via a radical cyclization cascade [31]. Building on this work, we report herein an atroposelective synthesis of

• diastereoselective approach for the synthesis of axially chiral biaryls through an electricity-powered cyclization cascade. The reactions employ easily assembled starting materials and afford functionalized imidazopyridine-based biaryls in good to high yields and diastereoselectivity. Reaction design. Scope of

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• stereochemical imprint of a TS on achiral products is not directly visible, there still can be a chiral cyclisation cascade behind these terpenes. This is true as well for examples featuring a mirror plane like the monoterpene 1,8-cineol (eucalyptol, 3), for which the absolute configuration of the intermediary

• products, showing that both enantiomers of NPP were converted with similar efficiency. These results clearly rule out (S)-NPP, but rationalise (R)-NPP as an intermediate in the cyclisation mechanism of BbS, and are in favour of the (S)-bisabolyl cation (A) to be deprotonated to 5 within the cascade

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• -ketoenamide and the pyridin-4-ol has been discussed earlier [21][22][23], but the essentials of the involved cascade reactions have to be presented again in order to understand the formation of the crucial β-ketoenamide intermediates (Scheme 2). The protonation of the primarily formed allenylimine A by the

• % yield (1:1 mixture of the two possible diastereomers). Probably due to the bulkiness of the acyl group, the migration to the nitrogen is strongly hampered and hence the three-component cascade almost completely stops at the stage of aminobutadiene C (see Scheme 2) that is hydrolyzed during work-up to

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• highly substituted olefins using acrylamides. However, most of them are limited to one-step coupling or annulation and just a single ring is formed [15][16][17][18][19][20][21][22]. Therefore, it is necessary to explore a new cascade annulation of acrylamides to construct a polyfused-heteroarene skeleton

Low-budget 3D-printed equipment for continuous flow reactions

• Jochen M. Neumaier,
• Amiera Madani,
• Thomas Klein and
• Thomas Ziegler

Beilstein J. Org. Chem. 2019, 15, 558–566, doi:10.3762/bjoc.15.50

• step reaction arrangement starting from pyranose 4 was set up. Scheme 4 shows this setup of a suitable cascade reaction in which DBU, trichloroacetonitrile and pyranose 4 were pumped through the first flow reactor (R1) followed by the addition of the alcohol and TMSOTf through the second reactor. Table

• glycosides 3–7 were obtained. To the best of our knowledge similar cascade flow glycosylations have not been described in the literature so far. Finally, the herein developed flow system devices could also be applied to the continuous flow preparation of glycosyl azides. For example, we were able to convert

• -budget lab equipment for continuous flow chemistry could be manufactured for under 300 €. With this equipment, consisting of Arduino controlled syringe pumps and microreactors, the preparation of glycosyl donors and glycosylation reactions were performed in a cascade fashion to show the viability of this

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• through a cascade of several reactions (Scheme 4, pathway a). The first step was the addition of thioacetamide to PBT 2 by subsequent nucleophilic attacks of S and N atoms. The formed compound 3 had a strong nucleophilic center – the exo-methylene group, which could attack the other molecule of compound 3

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• indole moiety to afford the target product 64 along with the regenerated Rh(III) catalyst. A silver-catalyzed intramolecular cascade amination/ring-opening/cyclization of a variety of substituted MCPs 69 was proposed by Fan and co-workers, which provided a simple and efficient way for the building of

• photoredox catalysis oxidative radical ring-opening and cyclization of cyclopropyl olefins 83 with bromides 84 for the synthesis of partially saturated naphthalenes 85 in moderate to excellent yields (Scheme 19) [97]. It was the first example for alkylation, ring-opening and cyclization cascade reaction of

• excellent enantioselectivity (Scheme 36) [116]. This transformation merged a stereocontrolled radical pattern with a classical ionic process in a cascade sequence. In 2018, Orellana et al. developed the Ag(II)-catalyzed ring-opening and functionalization of cyclopropanols 91 with electron-poor aromatic

Selective ring-opening metathesis polymerization (ROMP) of cyclobutenes. Unsymmetrical ladderphane containing polycyclobutene and polynorbornene strands

• Yuan-Zhen Ke,
• Shou-Ling Huang,
• Guoqiao Lai and
• Tien-Yau Luh

Beilstein J. Org. Chem. 2019, 15, 44–51, doi:10.3762/bjoc.15.4

• ][8][9][10][11][12][13][14][15] or from biscyclobutene [16] linked with a range of different rigid linkers. When a flexible linker is used, bisnorbornene derivatives undergo cascade metathetical cyclopolymerization giving the corresponding polynorbornenes with hammock-like pendants [17][18

• relevant peaks. We have previously found that two norbornene derivatives connected by a flexible linker 15 may undergo cascade ring-opening–ring-closing metathesis polymerization to give single-stranded hammock-like appended polynorbornenes 17 (Scheme 6) [17][18]. The linker in 8 is flexible, and

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• phosphoribosyltransferase; catalysis; enzyme; hypoxanthine phosphoribosyltransferase; multi-enzyme cascade; nucleotides; thermophiles; Introduction Bacterial phosphoribosyltransferases are used in multi-enzymatic cascades that perform nucleotide synthesis de novo [1][2]. Recently, we reported on the possibility of cascade