Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• under halofluorination conditions. We expected that the imide moiety of this molecule would fix the carbonyl oxygen atom in a position remote to the C=C bond to avoid cyclization. Indeed, the bromofluorination of tricyclic 19 was successful. However, the process required repeated reagent addition and

• . Since the treatment of the reaction mixture at reflux conditions significantly increased the yield, the formation of 22 may follow a radical pathway. Using a modified literature protocol [35], the tricyclic imide 24 was also prepared and investigated. In halofluorination reactions, the behavior of 24

• was inferior. Interestingly, the same type of tricyclic compound (rac)-28 was formed from all four substrates (Scheme 18). The stereochemistry of the product was determined using NOESY measurements. Since the structures of the substances in the mixture of (rac)-8a,b are unknown, a possible mechanism

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• efficiently via a triplet-mediated pathway without use of any external sensitizer. Similar to bicyclic systems, some of the tricyclic system like 1h yielded 1,2-AS product 2h under similar reaction conditions [16]. Initially we envisaged two mechanistic pathways: the oxa-di-π-methane (ODPM) path

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• )8 followed by the addition of NMO), and starting from the pure anti diastereoisomer of 1,7-enyne 20, the expected bicyclic enone was obtained in good yield and high diastereoselectivity (de > 95%). An attempt to extend the PKR to the formation of a fused tricyclic structure, starting from 1,7-enyne

• 21, was unsuccessful and no tricyclic product was formed. Bonnet-Delpon and co-workers reported the one-pot synthesis of several CF3-containing N-tethered amines in good yields (54–86% over 2 steps) [49]. These products were subjected to metathesis reactions in the presence of Grubbs catalyst

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• the construction of the tricyclic scaffold of phenanthrenes and their nitrogen-containing analogues, mainly phenanthridines. The adoption (in most cases) of visible light to promote the processes makes the photocatalytic approach one of the mildest methods available for the construction of these

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• with the use of succinic anhydride. The results are evidence of an unexplored method for the access of the aforementioned tricyclic annelated systems incorporating a bridgehead nitrogen atom. The structures and relative configurations of the new compounds were established by means of 1D and 2D NMR

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• used similar disulfide-catalyzed [3 + 2] cycloaddition reactions for the synthesis of polycyclic frameworks. The irradiation of vinylcyclopropanes with alkenes or alkynes in the presence of dibutyl disulfide afford the desired bi- or tricyclic products with 54–88% yield (Scheme 2) [6]. In 2014, Maruoka

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• underwent a thermal rearrangement to generate tricyclic isobenzofurans 313 through the ring-cleavage of the thietanes. It was assumed that the rearrangement was assisted through participation of the oxygen lone-pair electrons [17] (Scheme 57). The silicon-containing phenyl triphenylsilyl thioketone (316

• Synthesis via intramolecular photochemical [2+2] cycloadditions: In 1985, Machida’s group reported the intramolecular photo-assisted [2 + 2] cycloadditions of N-allylthiosuccinimides 327 applying 1 kW high-pressure mercury lamp irradiation under a nitrogen atmosphere, giving the highly strained tricyclic

• thietanes 328 [91] (Scheme 62). One year later, the same group reported the intramolecular photo [2 + 2] cycloadditions of 2-allyl-N-methyldithiosuccinimide (329) with the same irradiation source at room temperature for 1 h, generating another highly strained tricyclic thietane 330. 2-((6,6-Dimethylbicyclo

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis as a key step, we herein survey representative examples where this reaction is effectively associated with traditional chemical transformations to produce bioactive synthetic targets. Review Artemisinin and nanolobatolide Due to its biological relevance, artemisinin, a tricyclic compound bearing a

• key step, adding this protocol to the existing synthetic or hemisynthetic procedures. Along this line, Oguri et al. elaborated an excellent strategy for assembling the tricyclic diene scaffold of artemisinin and its analogs that combines classical transformations with tandem dienyne ring-closing

• catalyzed by Grubbs 2nd generation Ru-carbene, these intermediates then led to the tricyclic sesquiterpenoid-like scaffolds I–VIII (Scheme 4), as suitable precursors for the synthesis of artemisinin and its analogs (1a–c). After selecting the optimal tricyclic intermediate, the installation of the bridged

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• and 6b: Figure 2 and Table S2 in Supporting Information File 1). The BODIPY cores of 3a and 6b are almost planar with smaller mean-plane deviations (defined by the 12 atoms of the tricyclic ring system) of 0.075 and 0.025 Å, respectively. The meso-mesityl groups are oriented perpendicularly to the

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic Talaromyces sp. ECN211

• Ken-ichi Nakashima,
• Junko Tomida,
• Takao Hirai,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 290–296, doi:10.3762/bjoc.16.28

• , indicative of a tricyclic ring system in the structure of 1. HMBC correlations (Figure 2) from H-2 to C-4 (δC 107.4) and C-9a (δC 108.0), from H-4 to C-2 (δC 112.7), C-4a (δC 155.9), and C-9a, and from H3-11 to C-2 (δC 112.7), C-3 (δC 148.2), and C-4 (δC 107.4) indicated the presence of a tetrasubstituted

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

• that shows good overlap with drugs like levaquin, which is characterized by a complex tricyclic skeleton. The addition of a second aromatic ring, as the benzoyl or tosyl group of compounds 30–32, 34 and 35, increased the aromatic- and conjugation-related character of the structure, thus resulting in

• even more efficient in increasing the three-dimensional character of these compounds, as spiro tricyclic products were found to be more shifted towards the sphere-disc region of this chemical space, especially if compared to their corresponding starting materials (see Figure 4, compounds 5 and 26 with

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

• cationic species. For instance, remodeling the hydrophobic pocket of the active site by single-point mutation, epi-isozizaene (33) synthase was engineered to produce various linear, monocyclic, bicyclic, and tricyclic terpene skeletons (Figure 9b) [119][120][121]. Another prominent example is cyclooctat-9

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• DBE and thus requiring 1 to be tricyclic. The 1H and 13C NMR data also revealed the presence of one hydroxylated quaternary carbon (C-9), two aliphatic quaternary carbons (C-4, C-10), two oxymethines (C-1, C-6), one aliphatic methine (C-5), one oxymethylene (C-12), two aliphatic methylenes (C-2, C-3

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

• backbones. Thus, in the presence of presilphiperfolan-8-β-ol synthase (Bot2) a novel tricyclic product 70 was obtained from unnatural farnesyldiphosphate ether 69. The olfactory analysis revealed an ethereal, peppery and camphoric scent (Scheme 10) [39]. Future prospects of the fragrance industry will be

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• xanthone 6 [8]. A related strategy, adding lithium compound 7 to a preformed tricyclic system 8, was used by Nagano et al. to synthesize the Ge and Sn rhodamine analogues [14]. In a recent publication, Urano et al. synthesized the rhodamines 13–15 by coupling the triflate of xanthone 12 with boroxines 9b

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• deuterium labeling [33][34][35], to form the carbocation located at position C8 of dolabellatrienyl (B). By ring closure and formation of a novel C–C bond the tricyclic 5–8–5 ring system (C) is established. F107, F149, and the pyrophosphate moiety stabilize the carbocation at position C3 (Scheme 2 and

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• biosyntheses of known alkaloids, a “pyridoacridine family tree” which is claimed to be useful for designing total synthesis, but also for predicting yet undiscovered alkaloids from this chemotype [6]. Only two tricyclic benzo[c][2,7]naphthyridine alkaloids, perlolidine (6; from rye grass, Lolium perenne) [7

• natural products and analogues thereof. In combination with a Parham-type cyclization a novel approach to pyrido[4,3,2-mn]acridones could be shown. Marine pyridoacridine alkaloids amphimedine (1), ascididemin (2), kuanoniamine A (3), styelsamine D (4) and eilatin (5), as well as the two known tricyclic

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• (see Figure 2 and Supporting Information File 1) disclosed the structure of 6, bearing a novel, bridged tricyclic 1,5-methanopyrrolo[1,2-e][1,5]oxazonin-3-one ring system (Scheme 1). In contrast, submission of atorvastatin calcium trihydrate (1) to concentrated sulfuric acid for two hours at 60 °C

• elucidated by NMR and crystal structure analysis. The bridged tricyclic product 6 was formed with concentrated hydrochloric acid, whereas lactone 7 resulted from treatment with concentrated sulfuric acid. We propose mechanisms for the formation of the novel artefacts 6 and 7 here. But it has to be mentioned

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• -bromophenyl)imidazole (1i) with Se powder gave the corresponding tricyclic product 10 in low yield. Since the reaction conditions for the synthesis of the starting material 1 and the cyclization of 1 with Se powder are similar, we carried out a three-component reaction of benzimidazole, 1-bromo-2

• to be 304 nm, which is red-shifted by 21 nm compared with that of 11. The tricyclic compound 10 has a shorter λmax (297 nm). These results indicate the λmax is dependent on the number of rings. In 2-substituted derivatives (4–9), the maximum absorptions were very similar to each other (Table 2 and

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

• -phenylethylamine (49) to generate key tricyclic intermediates 51 and 52, a Pd(II)-catalyzed carbonylation–lactonization reaction of 9 to construct the butenolide (D-ring), and a Friedel–Crafts isopropylation to install the C-13 isopropyl group. Still, the construction of the C-5 trans junction A-/B-ring was

• mixture of 51 and 52, subsequent Pd/C-catalyzed hydrogenation and tetrabutylammonium fluoride (TBAF)-mediated desilylation yielding the desired tricyclic 54 (83% yield, 98% ee). Overall, the known intermediate 7-oxotriptophenlide 59 was obtained in an efficient, elegant and scalable way in 10 steps with

• key cyclization precursor ketoester 15, which was cyclized in the presence of SnCl4 to give tricyclic intermediate 83, followed by steps of functional group modification to install the butenolide (D-ring), and to finish the racemic synthesis of the key intermediate triptophenolide methyl ether (8) in

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

• the unlabeled and deuterated compounds, mechanisms for sesquiterpene formation in V. vinifera could be proposed and already known pathways could be confirmed or disproved. For example, the HS-SPME–GC×GC–TOF–MS measurements of fed sample material showed that the tricyclic sesquiterpene hydrocarbons α

• isopropyl group leads to the fragment with m/z = 166. At this point it becomes obvious why it can be assumed that the tricyclic sesquiterpene hydrocarbon α-cubebene is synthesized via (S)-(−)-germacrene D and not via (R)-(+)-germacrene D. Assuming the biosynthesis of α-cubebene takes place via (R

• ]. Tantillo and co-workers showed that germacrene D does not have to be involved in the formation of α-ylangene due to carbocation energetics. However, according to our results the formation of this tricyclic sesquiterpene hydrocarbon and its isomer β-ylangene occurs via the intermediate (R)-(+)-germacrene D

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

• 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

• coordinate. Highly mobile carbons are shown in red, moderately mobile carbons in yellow, and static carbons in blue. Phase I: 5/12/5 tricycle formation Based on our inherent mobility analysis, C1–C5, C15, C16, C20, C21 and C23 are static during 5/12/5 tricyclic formation in the biosynthesis of both

• biosynthetic outcomes in other terpene-forming reactions. We are currently applying this approach to sesterterpenes that are synthesized through a 5/6/11 tricyclic intermediate. Experimental All calculations were carried out using GRRM11 [21][22][23][24][25] with Gaussian 09 [26]. All TS structures were

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• with electron-poor alkenes occurs through a stepwise conjugate addition–cyclization process [23]. We were interested in the related quinolinium ylides that, on (formal) cycloaddition would provide pyrrolo[1,2-a]quinolines as products. These are tricyclic compounds consisting of a pyrrole ring fused

• tricyclic products 3 (Scheme 1) [41][49]. Similar examples with phenanthridinium and related ylides make use of ketones to stabilise the ylide [50][51][52][53][54]. The only exception (as far as we are aware) to the use of quinolinium ylides with ketones as stabilising groups are isolated reports with a

Selenophene-containing heterotriacenes by a C–Se coupling/cyclization reaction

• Pierre-Olivier Schwartz,
• Sebastian Förtsch,
• Astrid Vogt,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2019, 15, 1379–1393, doi:10.3762/bjoc.15.138

• -Wolff-Straße 13, 29699 Bomlitz, Germany 10.3762/bjoc.15.138 Abstract A new novel family of tricyclic sulfur and/or selenium-containing heterotriacenes 2–4 with an increasing number of selenium (Se) atoms is presented. The heterotriacene derivatives were synthesized in multistep synthetic routes and the

• heteroacenes via trimethylsilyl (TMS)-substituted selenolotriacenes, which served as intermediate building blocks [27]. In continuation of our work on heteroacenes, we now report synthesis and characterization of fused tricyclic selenium or selenophene-containing heteroacenes 2–4, which represent the so far