Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• (Scheme 15) [50]. Among the compounds tested, 1-naphthaldehyde (63) provided a photostationary mixture rich in the trans-diene (trans/cis ratio ≈ 13). A year later, the same group further studied the cis/trans isomerization of the piperylenes 61 and 62 utilizing energy transfer from the triplet states of

• state quencher, as well as by the lowered rate of the reaction in the presence of the triplet energy quencher 2,5-dimethylhexa-2,4-diene or pyridazines, additives with lower triplet state energies than 4-anisaldehyde (52). The fact that the solvent polarity did not affect the sensitivity of the process

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

• that enyne metatheses are atom economical processes driven by the enthalpic stability of the conjugated diene products. Depending on the steric requirements of the transition metal carbene and of the starting enyne, the intramolecular reaction can proceed either via ene–yne or yne–ene pathways to yield

• (Scheme 3 (c)) leads to the expected 1,3-diene (Scheme 3 (d–f)). A particular advantage of the enyne metathesis is that the stereoselectivity can be readily controlled by the intramolecular vs the intermolecular process. Among the vast array of bioactive organic molecules already synthesized through enyne

• 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

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• yields (Scheme 48). They proposed a mechanism in which LCu(I)–Si coordinates first with the triple bond, which eventually forms a monosilylated diene. The resulting organocopper species then participates in a second catalytic cycle to furnish the disilylated products [86]. 2 Cu-catalyzed carbon–boron

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• semiochemicals. They have been frequently found as pheromones in lepidopteran species of the families Noctuidae, Arctiidae, Lymantridae, Geometridae and Erebidae [1]. (3Z,9Z)-6S,7R-Epoxyheneicosa-3,9-diene, a constituent of the female sex pheromone of the moth Tetanolita mynesalis (Erebidae) [2] is a

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

• presence of camphorsulfonic acid did not give the desired amine, supporting the hypothesis of steric hindrance at such position [57]. Similarly, Simmons–Smith cyclopropanation reaction [58] did not work, and so as for the cycloaddition reaction with Danishefsky’s diene, possibly due to steric hindrance

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• Zealand 10.3762/bjoc.16.15 Abstract A fast, protecting-group-free synthesis of dihydropyridinones has been developed. Starting from commercially available aldehydes, a novel one-pot amidoallylation gave access to diene compounds in good yields. Ring-closing metathesis conditions were then employed to

• generate the desired product. This stepwise addition was successful in affording an improved 88% yield of diene 5 as well as significantly reducing the overall reaction time (Scheme 3). Treatment of diene 5 under ring-closing metathesis conditions, using Grubbs I catalyst, then proceeded to generate the

• described above. Rewardingly, Hosomi–Sakurai allylation of the conjugated imine intermediate proceeded to afford the desired diene 10 in working yield (35%). The formation of diene 10 is significant as the corresponding α,β-enones and α,β-enals undergo exclusive conjugate addition under Hosomi–Sakurai

Synthesis and optoelectronic properties of benzoquinone-based donor–acceptor compounds

• Daniel R. Sutherland,
• Nidhi Sharma,
• Georgina M. Rosair,
• Ifor D. W. Samuel,
• Ai-Lan Lee and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2019, 15, 2914–2921, doi:10.3762/bjoc.15.285

• for C36H22N2O2, 515.1760; found, 515.1760. 4,4''-Bis(diphenylamino)[1,1':4',1''-terphenyl]-2',5'-dione (5): To a Schlenk tube equipped with a magnetic stirring bar were added 2,5-dibromocyclohexa-2,5-diene-1,4-dione (251 mg, 0.94 mmol, 1 equiv), 4-(diphenylamino)phenylboronic acid (809 mg, 2.80 mmol

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

• pathway (dxs, idi, ispD, ispF, fps/ggps) or the entire exogenous MVA pathway in E. coli have been demonstrated to raise terpene titers dramatically [77] and have been applied for the production of several plant-derived terpene backbones, including amorpha-4,11-diene (21) [78][79] and taxadiene (22, Figure

• [116]. In some cases, bacterial TCs are able to accept oligoprenyl diphosphates with different lengths. Spata-13,17-diene (39) synthase is an extreme example that can convert FPP (9), GGPP (10), and geranylfarnesyl diphosphate (GFPP, 11) into sesquiterpenes, diterpenes, and sesterterpenes, respectively

• oxidoreductase in the heterologous host S. avermitilis SUKA16. The native pathway is highlighted in blue. TC promiscuity and engineering. a) Spata-13,17-diene (39) synthase (SpS) can take C15 and C25 oligoprenyl diphosphate as substrates in addition to its C20 natural substrate. b) Selected examples of epi

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

• inexpensive carbon sources. Prominent examples of optimized terpene production pathways in E. coli are taxadiene, a precursor of the anticancer drug taxol [28], amorpha‐4,11‐diene, an antimalarial drug precursor [29], and cyclooctatin [30]. The scope of this review encompasses a detailed consideration of the

• the literature, other TPSs with modified aspartate‐rich motifs have been reported, encompassing selina‐3,7(11)‐diene synthase: 82DDGYCE87 [57] and (+)‐T-muurolol synthase: 83DDEYCD88 [58]. It is commonly observed that the aspartate-rich motif resides at the lower part of α-helix D in the structure of

• [11]. Structural information on selina-4(15),7(11)-diene synthase (SdS), revealed that upon substrate binding by an induced fit mechanism, R178 changes its side chain conformation thereby approaching and interacting with the diphosphate function of the substrate analogue and forming a salt bridge to

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• esters 9 and 12 (bpy – 4,4’-di-tert-butyl-2,2’-dipyridine; COD – cycloocta-1,5-diene; NBS – N-bromosuccinimide, DCM – dichloromethane). Photoswitchable diarylethenes AsTh1, SyTh1, AsTh2, SyTh2, AsOTh1, SyOTh1, AsOTh2, and SyOTh2 synthesized via a Suzuki–Miyaura coupling. Conditions: 60 °C, argon

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

• reduction conditions to afford cyclohexa-1,4-diene 13 [9]. Enantioselective Sharpless dihydroxylation proceeded in good chemoselectivity but with modest yield and optical purity (25% ee). Unfortunately, all attempts to improve the enantioselectivity of this reaction failed. We discovered, however, that at a

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• ). Remarkably, this was the first example to afford (Z)-allyl fluorides (Z:E ratio > 20:1). In 2015, Nguyen et al. [95] explored the asymmetric fluorination of racemic, secondary allylic trichloroacetimidates with Et3N·3HF using a chiral-diene-ligated Ir complex (Scheme 47). This process proceeded under mild

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• engineering; terpenes; Introduction Amorphadiene synthase (ADS) from Artemisia annua is a key enzyme involved in the biosynthesis of the antimalarial sesquiterpene drug artemisinin (1) [1][2][3][4]. ADS catalyses the Mg2+-dependent conversion of farnesyl diphosphate (FDP, 2) to amorpha-4,11-diene (3) with

• closure to form the bisabolyl cation (6). A [1,3]-hydride shift to form carbocation 7 and 1,10-ring closure yield the amorphyl cation (8). Finally, deprotonation generates amorpha-4,11-diene (3) [8][9]. Several sesquiterpene synthases including ADS accept FDP analogues containing a variety of heteroatoms

• : Mass spectra of 26 and 27. 1H NMR spectrum (400 MHz, CDCl3) of 12-methoxy-β-sesquiphellandrene (26) and 12-methoxyzingiberene (27) produced by ADS from 12-methoxy-FDP (12). Mechanism of the ADS-catalysed conversion of FDP (2) to amorpha-4,11-diene (3), a biosynthetic precursor of artemisinin (1

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

• reported as intermolecular cycloaddition reactions, there are some interesting reports regarding the intramolecular cycloaddition of fulvenes, summarised in Table 1. For the intramolecular cycloadditions of pentafulvenes, the fulvene has been reported to react as both diene and dienophile depending on the

• length of the extended pentafulvene chain, and the role of the fulvene in the reaction (diene or dienophile) [127]. In these examples, kigelinol and neoamphilectane are of great interest in biomimetic and natural product chemistry, as they exhibit antitrypanosomal [128][129] and antimalarial [130

• function as 2π, 4π, 6π or 10π components (Table 2). This functionality is dependent both on the other reactant partner, and the electronic effects of the fulvene substituents [96][97][98][99][153][156]. As an example, in [4 + 2] cycloadditions, fulvenes will participate as 4π components (diene), provided

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• two new alkane derivatives colisiderin A and (7E,9E)-undeca-7,9-diene-2,4,5-triol [35] and from the organic extract of the red alga Laurencia obtusa [36]. However, to the best of our knowledge, ours is the first report of these brasilane-type sesquiterpenes obtained via biosynthetic genes. Metal ion

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

• was isomerized in the presence of base and dehydrated to give diene 45. Reduction of 45 with 10% Pd/C afforded 8 in good yield (60%) after recrystallization. Benzylic oxidation of 8 (CrO3/HOAc, 45%), followed by C-14 ether cleavage (BBr3) and subsequent sodium borohydride reduction afforded 46 with

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

• selina-3,7(11)-diene and γ-elemene via (E,E)-germacrene B are consistent with our results (Scheme 6) [9]. In Figure 9 the recorded mass spectra of d0-γ-elemene and d9-γ-elemene are shown as examples. Biosynthesis of guaiazulene, δ-elemene, guaia-6,9-diene and δ-selinene The formation of the aromatic

• described by Steele et al. for the formation of guaia-6,9-diene and δ-selinene via germacrene C could also be confirmed by feeding experiments (Scheme 7) [9]. Biosynthesis of (E)-β-caryophyllene and α-humulene The biosynthetic pathway postulated by Boland and Garms for the formation of (E)-β-caryophyllene

• A. *An incorporation of deuterium atoms into (+)-valencene could be detected, but due to coeluting substances no characteristic mass spectrum of d9-(+)-valencene could be obtained. Mechanistic rationale for the generation of the sesquiterpene hydrocarbons γ-elemene and selina-3,7(11)-diene via (E,E

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

•  2). This compound in reaction with AlCl3 without benzene afforded a mixture of allyl alcohol Z-9 and diene E-10a after aqueous work-up (Table 2, entries 1 and 2). The amount of 2.1 equivalents of AlCl3 is sufficient for activation of this transformation (compared to the amount of AlCl3 in entries 1

• and 2, Table 2). On the other hand, 1 equivalent of AlCl3 is not enough to activate allene 1a; thus, under these conditions, only acid 2 was obtained as a product of the hydrolysis of starting compound 1a (Table 2, entry 3). Methanolysis of the reaction mixture gave diene E-10b (Table 2, entry 7). The

• 1 equivalent of AlCl3 (see Table 2, entry 3). Addition of more than 1 equivalent of AlCl3 (2–5 equivalents) to a solution of 1a in CD2Cl2 in an NMR tube resulted in an immediate formation of diene E-14 as a part of a complex mixture (Scheme 8, see Supporting Information File 1 for NMR). Compare with

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• system, where the corresponding diene 39 was isolated in up to 36% yield. In our earlier studies, typically approximately equimolar quantities of tartrate and alkylating agent were used, but with the halide now being synthetically more valuable, efforts focused on conditions which gave the best yields

• temperature before slow addition of the pre-cooled LDA minimised diene formation, with the excess residual unreacted tartrate being most conveniently removed by distillation on large-scale. Our second synthesis of DDSQ (2) introduced the full side-chain through alkylation with iodide 40 to give the alkylated

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

• : 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

• hydrogen bonding organocatalyst for the reaction between 1-dimethylamino-3-tert-butyldimethylsilyloxy-1,3-butadiene (Rawal’s diene) and aldehydes with excellent enantioselectivities (aromatic aldehyde: up to 86–98% ee) in 2003 [27]. Activation via a single-point hydrogen bond between one of the hydroxy

• form strong hydrogen bonds could perform the same catalytic role in oxo-DA reactions as reported in the literature. Inspired by Rawal’s work on TADDOL and BAMOL organocatalysts, we, in this work, have adopted a similar reaction of Rawal’s diene with benzaldehyde as a starting point of our study and

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• , ring-opening metathesis polymerization – ROMP and acyclic diene metathesis – ADMET. This motivates the investigations into the development of new, efficient, stable, and highly selective catalytic systems based on ruthenium complexes. However, in reality, a limited set of commercially available

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

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• due to cycloaddition with an olefin group in 2j (Table 3, entry 9). When 2k was applied in the reaction, the addition product was obtained with a yield of 44% with the alkyne group being involved in the reaction (Table 3, entry 10). The reaction with 2l mainly produced 1,3-diene product 4l with a

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• tags. c) PEG-tethered catalysts. Chemical structure and components of amphiphilic molecule PTS and derivatives. In vivo metathesis with an artificial metalloenzyme based on the biotin–streptavidin technology. Most common metathesis reactions. Ring-opening metathesis polymerization (ROMP), acyclic diene

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• silsesquioxanes (POSS) and POSS-containing polymeric materials. Three types of processes, i.e., cross metathesis (CM) of vinyl-substituted POSS with terminal olefins, acyclic diene metathesis (ADMET) copolymerization of divinyl-substituted POSS with α,ω-dienes and ring-opening metathesis polymerization (ROMP) of

• metathesis in chemistry of unsaturated derivatives of POSS is limited to three types of processes, i.e., cross metathesis (CM) of vinyl-substituted POSS with terminal olefins, acyclic diene metathesis (ADMET) copolymerization of divinyl-substituted POSS with α,ω-dienes and ring-opening metathesis

• catalyst permits selective CM. Another metathetic transformation – acyclic diene metathesis copolymerization – permits introduction of a POSS group to the copolymer main chain. This methodology has not been thoroughly studied so far. In turn, ring-opening metathesis (co)polymerization is a convenient tool