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

• possibility of using a copper-catalyzed one-pot 1,4-addition of vinylmagnesium bromide to sugar-derived cyclic α,β-unsaturated ketones (such as 9), followed by an aldol reaction with an optically pure derivative of but-2-enal 10 to obtain a mixture of diastereomeric dienes, such as 11 (Scheme 2). As a result

• result of this three-step sequence of reactions, derivatives 15 and 16 were formed, respectively. Addition of vinylmagnesium bromide to 15 and 16 afforded the corresponding dienes, which – without further purification – were subjected to the RCM reaction with the Hoveyda–Grubbs II generation catalyst. As

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

• Juliane Adrian Leona J. Gross Christian B. W. Stark Fachbereich Chemie, Institut für Organische Chemie, Universität Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany 10.3762/bjoc.12.200 Abstract The direct oxidative cyclization of 1,5-dienes is a valuable synthetic method for the (dia

• the trans-isomer from cis-THFs see the examples section below). For all three procedures (using Mn(VII), Ru(VIII) and Os(VIII)) the scope of the reaction is very broad and a large number of 1,5-dienes with any kind of substitution pattern and double bond geometry have been used as substrates [4][5][6

• ][16][17]. In addition, for Ru(VIII) [17][18][19] and Mn(VII) [21] it has been shown that also 1,6-dienes serve as substrates and can thus be directly converted to tetrahydropyrans [20][21][22]; ruthenium tetroxide even oxidizes 1,7-dienes to oxepans [23]. However, it has to be noted that the latter

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

• 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

• , requiring a detailed examination of the kinetic versus thermodynamic effects. The nitroso hetero-Diels–Alder reaction involves the formation of the 3,6-dihydro-2H-1,2-oxazine scaffold 3 from nitroso dienophiles 1 and dienes 2 in a [4 + 2] cycloaddition reaction (Scheme 1). The first nitroso hetero-Diels

• regio- and stereoselectivity of the hetero-Diels–Alder reaction as well as the possibility of controlling the regio- and stereoselectivity of 3,6-dihydro-2H-1,2-oxazine formation. Nitroso compounds and dienes Nitroso compounds: Nitroso compounds are highly reactive dienophiles often used for the hetero

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ) or versipelostatin A (153) result from formal [4 + 2] cycloaddition reactions between exo-methylene groups and conjugated dienes. The required exo-methylene groups are installed by formal dehydration of 5-hydroxymethyltetronates. Leadlay et al. have confirmed that the respective reaction in

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• 4:1 in the presence of 4 Å molecular sieves (Scheme 59) [97]. A sequential three-component enamine–azoene annulation reaction of primary aliphatic amines 292, activated methylene compounds 293, and 1,2-diaza-1,3-dienes (DDs, 294) has been reported to give polysubstituted pyrroles 295 (Scheme 60) [98

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• (MeCN)3PF6-catalyzed variant of the same reaction that proceeds even at room temperature [10]. The ruthenium process differs from the initially-discovered palladium reaction in that it produces cyclic 1,4-dienes exclusively; no olefin isomerization is detected (Scheme 1, path b). Moreover, ruthenium can

• simple 1,6-enynes displayed a broader scope than Mikami’s palladium system, although none of the examples contained a quaternary stereocenter [25]. Asymmetric enyne cycloisomerization reactions can be extended beyond the construction of 1,4-dienes, depending on the transition metal used and the adjacent

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• also point out that the 66:67 ratio was 2:1 regardless of the rhodium source (Rh2(OAc)4, Rh2(pfb)4, Rh2(TFA)4, Rh2(TPA)4) or solvents (hexane, benzene) used in this reaction. The dienes 100a–d were submitted to 2nd-generation Grubbs–Hoveyda catalyst (101), under dichloroethane reflux, to afford the

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• -fused pyran-3-ones and the results are reported herein. Results and Discussion For a long time, the Diels–Alder reaction of simple heterosubstituted 1,3-dienes has been considered a standard procedure to prepare highly functionalized ring systems [28]. Taking advantage of diazalactones to act as the

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• spectroscopic difference between these molecules and how these compared to analogous steroids whereby the cyclopropane group in the A-ring is replaced with a conjugating C=C double bond. To cut a long story short, vinyl cyclopropanes are conjugated, albeit to a lesser degree than dienes, and NMR, IR and UV–vis

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• , the asymmetric Diels–Alder (D–A) reaction between the N-sulfonamide-3-hydroxy-2-pyridone-based dienes 52 and different dienophile substrates was developed using the bifunctional cis-2-trialkylaminoindanol organocatalyst ent-41 [56]. We show herein the reactivity of this family of dienes with several

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• malononitriles 104 and α,α-dicyanoalkenes 105. The process yielded highly functionalized spiro-oxindole dienes 106. The products were obtained in good to excellent yields (up to 97%) and enantioselectivities (up to 96%), but the diastereoselectivities were moderate (up to 7.9:1) (Scheme 34) [53]. In 2015, Soós

Thermal and oxidative stability of Atlantic salmon oil (Salmo salar L.) and complexation with β-cyclodextrin

• Daniel I. Hădărugă,
• Mustafa Ünlüsayin,
• Alexandra T. Gruia,
• Cristina Birău (Mitroi),
• Gerlinde Rusu and
• Nicoleta G. Hădărugă

Beilstein J. Org. Chem. 2016, 12, 179–191, doi:10.3762/bjoc.12.20

• with the corresponding saturated compound, i.e., stearic acid. Furthermore, it was observed that the concentration of conjugated dienes (not counted as PUFAs) remarkably increased after oxidative degradation of fish oil [17][21]. These studies also support our results on thermal and oxidative

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify. Keywords: chromane derivatives; metathesis catalyst; nitrogen heterocycles; olefin metathesis; Ru-carbene; Introduction Olefin metathesis is

• potency of the new catalyst 9 was tested not only in standard, model metathesis reactions but was also examined in more demanding systems, such as conjugated dienes and polyenes (Table 4). The CM reaction between alkene and diene (or polyene) often suffers from low regio- and stereoselectivity control

• reactions of dienes with different olefins as efficiently as commercial Grubbs 2nd generation and Hoveyda–Grubbs 2nd generation complexes 1 and 2. Complex 9 catalysed the reactions of ethyl 3-methylhexa-2,4-dienoate in a completely selective manner taking into account product regio- and stereoselectivity

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• -catalyzed allyl–allyl cross-coupling of allylmetal species with allylic electrophiles represents one of the powerful methods to establish 1,5-dienes. These compounds are abundant in natural terpenes as well as highly versatile intermediates in organic synthesis [71][72][73]. However, highly enantioselective

• allyl Grignard reagents with allyl bromides, leading to chiral 1,5-dienes in good yield and with high enantioselectivity (Scheme 30). Cu-catalyzed enantioselective allylic substitutions with silylboronates Enantioenriched allylsilanes are very useful building blocks in synthetic organic chemistry [76

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• trapped by hetero-Diels–Alder reaction with dienes [54][55], and detection of the resulting hetero-Diels–Alder adducts used to confirm the formation of free nitroso intermediates. Thus trapping experiments were conducted using isoprene (14) to investigate the formation of a nitroso species in this

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• . Different strategies for the construction of E- or Z-cyclononenes have been reported to date and common reactions are summarized in Scheme 3. Transition metal-catalyzed ([M] = Ru, Mo, W) ring-closing metathesis (RCM) reactions of 1,10-dienes A can be employed for the synthesis of cyclononenes. The E/Z

• commonly employed method for the synthesis of cyclononenes due to the predictability of the stereochemical outcome of the product. The construction of cyclononenes can furthermore be achieved by thermal [3,3]-sigmatropic rearrangements of 1,5-dienes C. When the reaction proceeds via a chairlike transition

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• catalyst (Scheme 15). The use of an acidic additive also allowed the synthesis of fused bicyclic imidazoles through a GII-catalyzed RCM reaction (Scheme 16) [53]. Only few examples of RCM involving dienes that contain N-heteroaromatics were described on non-protonated species. In 2001, in the course of

• hindrance may be invoked to explain the absence of catalyst deactivation (Scheme 24). Similarly, 15- to 18-membered ring macrocycles that incorporate an imidazole group were synthesized using a RCM of the corresponding dienes using GII as the catalyst (Scheme 25) [64][65][66]. By examining all these

Olefin metathesis in air

• Lorenzo Piola,
• Fady Nahra and
• Steven P. Nolan

Beilstein J. Org. Chem. 2015, 11, 2038–2056, doi:10.3762/bjoc.11.221

• -workers synthesized the first well-defined ruthenium(II) complex (5, Scheme 2) bearing a carbene moiety, able to perform ring-opening metathesis polymerization (ROMP) reactions of low-strained olefins [34][35] and ring-closing metathesis (RCM) reactions of functionalized dienes [36]. In the solid state

• stability to air and water, compared to Grubbs 1st and 2nd generation catalysts [7]. RCM reactions were performed in air with 5 mol % of the catalyst, showing high yields for terminal dienes (Table 6, entry 1). In the absence of SIMes, increasing the olefin substitution led to low yields in all catalytic

• catalysts in technical grade solvents.a RCM and ene–yne reactions catalysed by 93a–f and 94 in air.a Yield (%) of RCM reactions using catalysts 105a–f, 106a–f and 107a–f in air.a RCM of representative dienes catalysed by 108a–c under air.a RCM of N-allyl-N-(methallyl)tosylamide (79) with complexes 111a–f in

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• -3-carboxylic acid derivatives 3, constrained analogues of tryptophan, could be synthesized by Diels–Alder reactions between 2-vinylindoles 1 [22] as dienes and methyl 2-acetamidoacrylate (dehydroalanine) 2 [23] as dienophile (Scheme 1). Reported [4 + 2] cycloaddition reactions of methyl 2

• -acetamidoacrylate (2) and its congeners with cyclic/acyclic dienes and azadienes occur under conventional heating or microwave irradiation [24]. Moreover, the use of titanium tetrachloride as Lewis acidic promoter has been reported [25]. Finally, simple functionalization reactions of indoles with 2 are reported in

• efficiency (Table 2, entry 4). As a consequence, we choose toluene as solvent for further cycloaddition reactions. Under these conditions, alkyl- (Table 2, entries 5 and 6) and aryl- (entries 7 and 8) substituted dienes smoothly react with methyl 2-acetamidoacrylate (2) affording the desired cycloadducts in

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• under conditions which require high stability of the active species. Macrocyclization of dienes having low effective molarity provides access to a number of valuable musk-like compounds [27][28]. This type of transformation must be carried out at a very low concentration (usually <10 mM) in order to

• suitable for macrocyclization of dienes with low effective molarity. The diversity of Hoveyda-type complexes (Mes – 2,4,6-trimethylphenyl, DIPP – 2,6-diisopropylphenyl). Reaction profiles for RCM of DEDAM; toluene, 0.2 M, 18 °C, [Ru] 0.15 mol %; conversion determined by GC. RCM of 1 (toluene, 0.05 M, 25 °C

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• toluene, although prolonged reflux in toluene may cause degradation of the products. Small quantities (<10%) of isomeric products, presumed to be the corresponding 2Z,4E-dienes of 11a, 11b and 11c, were observed in the reaction mixtures derived from the primary alcohols. Only barely trace amounts of Z

Design and synthesis of propellane derivatives and oxa-bowls via ring-rearrangement metathesis as a key step

• Sambasivarao Kotha and
• Rama Gunta

Beilstein J. Org. Chem. 2015, 11, 1727–1731, doi:10.3762/bjoc.11.188

• otherwise difficult to synthesize following conventional retrosynthetic routes. This methodology can easily be extended for diversity-oriented synthesis [37] by employing different dienes and dienophiles during the DA reaction sequence. RRM route to propellane derivatives and oxa-bowls. Synthesis of the oxa

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• to generate conjugated 1,3-dienes under mild conditions. These 1,3-dienes are versatile building blocks suitable for further non-metathetic transformations, either in a step-wise or a tandem fashion. Thus, the enyne metathesis methodology has become a powerful tool for the generation of carbon–carbon

• new example of this tandem protocol CEYM–IMDAR with alkynes and α,ω-dienes as starting materials is reported, which will give access to a new family of linear bicyclic carbo- and heterocyclic scaffolds. We envisioned that the initial CEYM would occur in the electronically neutral olefin to generate

• the corresponding triene intermediate, which would evolve under the reaction conditions through the cycloaddition event to render the final products (Scheme 1). Results and Discussion The use of 1,5-, 1,6- and 1,7-dienes in cross metathesis-type transformations is not trivial since chemoselectivity

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• diverse crownophanes by using a cross-enyne metathesis and Diels–Alder (DA) reaction as key steps. Here, the macrocycles 146 and 149 were subjected to a cross-enyne metathesis protocol with ethylene to generate the dienes 147 and 150, respectively. These dienes were subjected to a DA reaction with