Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• reactivity is mainly due to the resonance energy gained by formation of a benzene ring in the cycloaddition product (Scheme 1) [6]. Isobenzofurans have been extensively used as 4 electron (diene) components in Diels–Alder reactions, and moreover in other cycloaddition reactions such as [4 + 3], [4 + 4], [8

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• configuration, thereby facilitating an intramolecular cyclization to a cyclodeca-1,5-diene by electrophilic attack of the allylic carbocation onto the corresponding double bond. A 1,3-hydride shift by Wagner–Meerwein rearrangement followed by another cyclization would then give rise to an octahydronaphthalene

• in an actinomycete led to a product, which was identified as the soft coral-derived diterpene obscuronatin [25][26]. The biosynthesis of this compound can be easily rationalized via the proposed herpetopanone pathway (route b in Figure 4). Following the formation of the cyclodeca-1,5-diene

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• -dienes such a buta-1,3-diene, isoprene, cyclopentadiene and anthracene. In all cases the reaction occurred at elevated temperature and afforded the expected cycloadducts in good to excellent yields [41]. The problem of the configuration of the substituents has not been discussed, but it seems likely that

• observed by 1H NMR spectroscopy [8]. Similar systems were prepared on solid phase and used as a new molecular recognition system [44]. The [4 + 2]-cycloaddition reactions of E- and Z-1b with electron-rich 1,3-dienes have been studied extensively by Sustmann and collaborators. Thus, 1-methoxybuta-1,3-diene

• reacted with both dienophiles in a stereospecific manner, and in both cases mixtures of two stereoisomeric cyclohexenes with preserved stereochemistry in the dienophile fragment were obtained [45]. On the other hand, reactions with 1,1-dimethoxybuta-1,3-diene (42) led, in both cases, to similar mixtures

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• , including dichloromethane, is sold under the trade name Brom-55 and used as swimming pool sanitizer, as industrial brominating agent for ethylene propylene diene monomer rubber to improve ozone resistance, as additive in plastics to promote photodegradation and as a fungicide to preserve fresh fruits [27

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• 200 and 300 °C, but some structural changes in the diene, such as the anionic oxy-Cope transformation allows the reactions to happen at temperatures below 0 °C [9]. The Cope rearrangement is a [3,3]-sigmatropic reaction and in general, occurs through a single transition state (TS), which has, normally

• , a chair conformation due to the higher energy of the boat conformation [2][7][10][11][12][13][14][15][16][17][18][19]. In this mechanism, the electron density of the TS is delocalized into the six carbon atoms [20][21][22]. However, if the diene contains free radical stabilizing groups, this

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• previously reported to have germacrene A synthase activity during heterologous expression in Escherichia coli, was identified by extensive NMR-spectroscopic methods as 18-hydroxydolabella-3,7-diene. The absolute configuration of this diterpene alcohol and the stereochemical course of the terpene synthase

• reaction were addressed by isotopic labelling experiments. Heterologous expression of the diterpene synthase in Nicotiana benthamiana resulted in the production of 18-hydroxydolabella-3,7-diene also in planta, while the results from the heterologous expression in E. coli were shown to be reproducible

• neighbours. Diagnostic NOESY correlations between H11 and H2β, H3 and H7, between H12 and H2β, and between H10α and H15 established the relative configuration of 3, resulting in the structure of (1R*,3E,7E,11S*,12S*)-18-hydroxydolabella-3,7-diene and identifying the terpene synthase from C. pinensis as 18

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• functionalized alkene 14 which is suited for a sequential cross-coupling strategy (Scheme 2). Under the catalytic conditions, we did not encounter isomerization of the alkene and diene configurations in vinyl boronate 13. The preparation of the newly modified western fragment started from known IMDA product 9 [7

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• three dimensional conformation of the archazolids by NMR methods, molecular modelling and chemical derivatizations [59][60]. During these studies, they became aware that C2–C5 diene of acyclic analogs would be very labile towards isomerization. However, such processes would be suppressed in the

• was planned which would likewise set the labile C2–C5 diene and thus concomitantly stabilize this functionality by macrocyclic constraints. Menche’s total synthesis of archazolid A Synthesis of the north-eastern fragment As shown in Scheme 3, the construction of the north-eastern fragment 5 relied on

• synthesis, also on highly elaborate substrates. Considerable efforts were invested before the challenging Heck coupling with the thiazole fragment 6 could be effected with useful selectivities. Besides the desired E,E-diene 34 formation of other double bond isomers both in the southern and northern part of

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• synthase domain indicating different catalytical properties. The natural product of PaFS is fusicocca-2,10(14)-diene, an intermediate in the biosynthesis of the phytotoxin fusicoccin A by P. amygdali. Interestingly, a recent work by Qin and co-workers [71] even revealed the conversion of a fungal diterpene

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• + 2]-cycloaddition between a diene and singlet oxygen. The endoperoxides were dihydroxylated and protected to provide a series of endoperoxide building blocks for organic synthesis, with potential use as precursors for the synthesis of branched azasugars. Preliminary exploration of the chemistry of

• . Results and Discussion We set out to synthesise two diene substrates for a photochemical [4 + 2]-cycloaddition with singlet oxygen to provide two different endoperoxides (Scheme 1, n = 1–2). Based on literature precedent Boc-protection was utilised for the amino group (Scheme 2) [13][14]. Moreover, the

• TEMPO, whereas oxidation of 6 using the Parikh–Doering method gave a good yield of aldehyde 10. Next, aldehydes 7, 9 and 10 were subjected to a Mannich reaction using the method by Erkkilä and Pihko to give the α,β-unsaturated aldehydes 11–13 in good yields [20]. The final step of the diene synthesis

Unpredictable cycloisomerization of 1,11-dien-6-ynes by a common cobalt catalyst

• Abdusalom A. Suleymanov,
• Dmitry V. Vasilyev,
• Valentin V. Novikov,
• Yulia V. Nelyubina and
• Dmitry S. Perekalin

Beilstein J. Org. Chem. 2017, 13, 639–643, doi:10.3762/bjoc.13.62

• cycloisomerization in the presence of the cobalt catalytic system CoBr2/phosphine ligand/Zn/ZnI2 giving cyclohexene, diene or cyclopropane structures depending on the type of the phosphine ligand. This unpredictable behaviour suggests that, although the availability of the cobalt catalytic system is appealing, the

• the diene compounds 3a,b in 90–95% yields. These compounds were also obtained using a 1,2-bis(diphenylphosphino)benzene (dppbz) ligand. Despite the extensive studies of enyne transformations, this type of cyclization has been achieved only recently, using a cyclobutadiene rhodium complex as a catalyst

• -membered metallacycle 7, which can undergo reductive elimination to give the cyclohexene 2, or β-hydride elimination followed by the reductive elimination to give the diene 3. It may be speculated that the steric crowding in the intermediate 7 determines the direction of the reaction. In contrast to the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , this compound polymerizes rapidly even at low temperatures, such as −50 °C. Therefore, until 1989 abicoviromycin (168) has not been successfully synthesized. The unit which probably determines the reactivity and unstability of abicoviromycin (168) is the diene-imine fragment. Due this fact, the authors

• similar way to synthesize 5-hydroxy substituted 1-indanone 250 by utilizing the 1,3-diene 248 and the sulfoxide 249, has been described by Danishefsky et al. [98]. As a result of the cycloaddition, 5-hydroxy-1-indanone (250) has been obtained in 68% yield (Scheme 69). Lee, Kim and Danishefsky have

• synthesized halogenated 1-indanones 253 from 2-halogenocyclopent-2-enones 252 and diene 251 [99]. As a result of the Diels–Alder reaction, bromo- and chloro-substituted 1-indanones 253a and 253b have been obtained in 91% and 72% yield, respectively (Scheme 70). Harmata et al. have synthesized 1-indanones 257

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• 1,3,6,8-tetraenes. Contrary to related decarboxylative coupling reactions, an anion-stabilizing group is not required adjacent to the carboxyl group. Of mechanistic importance, it appears that both the diene of the acid and the diene of the alcohol are required for this reaction. To further understand

• this reaction, substitutions at every unique position of both coupling partners was examined and two potential mechanisms are presented. Keywords: decarboxylation; diene; dienoate; palladium; pentadienyl; tetraene; Introduction The construction of sp2–sp3 carbon–carbon bonds remains a difficult and

• ], nitro [26][27], or alkyne [21][28][29][30][31][32], Scheme 1), or use an aryl carboxylate [33][34] which typically requires the assistance of silver or copper(I) salts for the decarboxylative step. It is rare to use a pentadienyl electrophile [35], or to have a diene or simple alkene adjacent to the

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• . Rojas et al. proposed a convenient two-step pathway for the preparation of alkyl α,ω-dienes 3. These dienes are well-known precursors in ring-closing metathesis (RCM) and acyclic diene metathesis (ADMET) chemistry [32]. They first reported the quantitative α-alkylation of primary nitriles 1 [33]. In a

• second part of their work, they developed adequate conditions to carry out the decyanation reaction without olefin isomerization [18]. They explored several methods for the preparation of 12-butyltricosa-1,22-diene 3 (R = n-C4H9). The reaction was carried out in a slurry of K/Al2O3 in hexane, hexane

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• fragrances are based on myrcene, such as geraniol, nerol, linalool, menthol, citral, citronellol or citronellal [3]. The terminal diene moiety present in myrcene allows for a reaction with a suitable dienophile following the Diels–Alder reaction mechanism. Dahill et al. describe the synthesis of the Diels

• . Results and Discussion The solution-phase Diels–Alder reactions presented herein follow the general reaction pathway shown in Scheme 1. The conjugated diene myrcene (1) was reacted with a series of dienophiles 2 to form the Diels–Alder adducts 3. Before investigating this reaction for continuous-flow

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• catalysts for aza-Diels–Alder reactions of Danishefsky’s diene with imines (Scheme 5) [52]. A variety of ammonium salts (L7–L10) including chiral cinchonidine derivatives L7 and catalyst L10 were found to promote the reaction in low-to-good yields albeit with no enantioselectivity. Although it is perhaps

• atoms covalently bonded to a benzylic carbon (Scheme 8). In 2016 Maruoka and Shirakawa followed up the aforementioned studies by demonstrating that tetraalkylammonium salts L5, L6, L11 and L12 as well as TBAI could activate imines toward aza-Diels–Alder reaction with Danishefsky’s diene (Scheme 9) [51

• coordinating TfO− anion did not accelerate the cycloaddition. In 2015, Takeda, Minakata and co-workers demonstrated that 2-iodoimidazolium salt L24 could serve as an efficient catalyst of the aza-Diels−Alder reaction of aldimines and Danishefsky diene (Scheme 19) [90]. Other organohalides such as

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• theoretically upper limit of 50%. We discovered that 6, sold by Acros Organics as racemic compound, was actually enriched in the desired (R)-enantiomer (see Supporting Information File 1 for optical rotation values). Diene (R)-9 was obtained by reduction of the epoxide 6 with LiAlH4 to form alcohol (R)-7

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• 1,4-addition of vinylmagnesium bromide to sugar-derived cyclohexenone, followed by an aldol reaction with a derivative of but-3-enal. The obtained diene is then subjected to an assisted tandem catalytic sequence: ring-closing metathesis with the subsequent reuse of the Ru-catalyst in the syn

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• Diels–Alder reaction selectivity [28]. The DAR of cyclopentadiene with p-benzoquinone is a well-known example of cycloadditions, and some results can be found on the control of the selectivity to the different isomers. In homogeneous phase, equimolar amounts of diene and dienophile afford two isomers

• second molecule of the diene to give again the kinetic endo-endo isomer. It is remarkable that neither the thermodynamic exo isomer nor the secondary exo-endo and exo-exo products were detected under our reaction conditions. Thus, the observed products, endo-endo and endo-exo are obtained in different

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• . Likewise, syntheses of fragments of natural products applying an oxidative cyclization protocol [1][2] and sequential epoxidation/cyclization procedures [3] are not in the scope of this article and are therefore not covered. Previous review articles concerning oxidative diene cyclization chemistry can be

• = Ac) or neryl acetate but seemed to be fairly general to other 1,5-diene substrates. Finally, they speculated on possible intermediates which may account for the outcome and the overall stereoselectivity of this unusual reaction. A mechanism, however, was not provided (vide infra). To date it is

• protocols using the three different d0-metals are highly diastereoselective (vide infra) and have been shown over the past decades to be applicable to a broad range of starting materials. Mechanistic aspects, stereochemistry and substrate scope of the direct oxidative diene cyclization Intrigued by the

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• standard Ugi–Smiles adducts 3 (Table 3). The lack of oxatricyclic epoxyisoindoline formation is not surprising, given the more remote relative proximity of the diene and dienophile. Propargylamine and 3-butenylamine were also satisfying partners with 3-furaldehyde in this process. Ugi–Smiles reactions with

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• , Czech Republic Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA 10.3762/bjoc.12.184 Abstract The hetero-Diels–Alder reaction between a nitroso dienophile and a conjugated diene to give the 3,6-dihydro-2H-1,2-oxazine scaffold is useful for the synthesis of

• stereo- and regioselectivity for the synthesis of 1,2-oxazine scaffolds. Keywords: diene; hetero-Diels–Alder; nitroso compounds; regioselectivity; stereoselectivity; Review Introduction The hetero-Diels–Alder reaction represents one of the most important methods in organic synthesis, providing various

• biologically active compounds. It is a variant of the Diels–Alder reaction where either the diene or the dienophile contains a heteroatom. Hetero-Diels–Alder reactions between conjugated dienes and nitroso dienophiles affording 1,2-oxazines are utilized for the synthesis of many biologically active molecules

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• the substrate FPP is converted with a strict stereochemical course with respect to the fate of the diastereotopic methyl groups in FPP. These findings are in agreement with those reported for several other terpene cyclases [58][59][60], while the (1R,4R,5S)-guaia-6,10(14)-diene synthase from Fusarium

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• , Garner and co-workers have exploited a cycloaddition pathway between a poly-oxygenated diene and Garner’s aldehyde for constructing the carbohydrate core of amipurimycin [9]. Recently, Datta and co-workers reported the first synthesis of a fully-functionalized thymine analogue of amipurimycin, utilizing