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

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh3)4 as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3

• and/or HMBC measurements. The influence of the basic (13αE1OH, 13αE1OMe and 13αE1OBn) and new compounds 8–13 on the transport function of OATP2B1 was investigated by measuring Cascade Blue uptake (Table 3) [31]. 13α-Estrone (13αE1OH) itself displayed weak inhibitory action with an IC50 value above 50

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• compounds operate by inhibiting proteins or enzymes that regulate cell cycles, including cyclin-dependent kinases [9], tyrosine kinase [10], glycogen-synthase kinase and mitochondrial malate dehydrogenase [11]. These interesting biological activities led us to develop one-pot sequential or cascade protocols

• rearrangement of 6,7-dihydroindol-4(5H)-ones. However, after implementing this approach, an undesirable isomer was obtained [21]. Although a number of acid- [22][23] and metal-catalysed cascade processes [24][25] have been developed (for example, Pictet–Spengler [26] and Ugi-type reactions [27], the acyl

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• various potential drug targets present within pqs QS. These range from enzymes within the biosynthesis cascade of the signal molecules PqsABCDE to the receptor of these autoinducers PqsR (MvfR). This review shortly introduces P. aeruginosa and its pathogenicity traits regulated by the pqs system and

• been published based on the design and optimisation of pqs targeting QSI, which is the topic of this review. The biosynthetic cascade of the pqs QS system PQS is the abbreviation for Pseudomonas quinolone signal and actually refers to the signal molecule 2-heptyl-3-hydroxyquinolin-4(1H)-one (Figure 2

• including their own biosynthetic enzyme cascade (PqsABCDE). Together with PqsH and PqsL, which are under the control of LasR from the las QS system, these enzymes manage to build up PQS and related molecules from anthranilic acid (Figure 2). This initial building block can be provided either through the

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

• from an acyclic compound by a cascade radical process using Mn(OAc)3 [21], although a trans-fused ring system was formed. Also of note, is the approach of Mori [22] to a dihydroindenedione based on an initial cyclization of an allyl iodide in a 1,3-cyclohexanedione side chain via an allyl anion

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• action of QSSMs leads to the activation of NFκB signaling cascade, resulting in the upregulation of pro-inflammatory cytokines IL-6, IL-8, and TNFα. However, our results demonstrated that TNFα expression is inhibited by all tested QSSMs, excepting HHQ (Figure 5). The expression of inflammatory molecules

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• modulator effect of the conjugates The dissemination of tumor cells is an important aspect of the tumor progression and could significantly affect the success of the targeted tumor therapy, as well. The first crucial steps in metastasis cascade are the impaired adhesion contacts and in parallel the

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• product 4a. Its treatment with a solution of sodium hydroxide in water promoted a quantitative lactone-opening/decarboxylation cascade sequence, yielding 2,4-dihydronaphthalene 6a in quantitative yield without the need of chromatographic purification. Interestingly, scaffold 6a is a valuable intermediate

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• , including those reactions involving valuable C–C [7][8][9][10][11], C–heteroatom [12][13][14][15][16], heteroatom–heteroatom [17][18] bond formation as well as divergent cascade reactions [19][20][21][22][23], are presently taking place to guide the progress of sustainable organic synthesis. 1,2,3-Triazole

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• into carbonyls [8][9][10][11][12][13][14][15][16][17], and application to cascade or domino reactions [18][19]. More recently, our group has used benzyl epoxides for the photoredox generation of carbonyl ylides which are leveraged in the synthesis of cyclic ethers [20]. This work has led us to search