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

• –Kishi coupling of haloalkenes with aldehydes. The first synthesis of the unusual nine-membered carbocyclic ring was reported by Corey for the total synthesis of β-caryophyllene in 1963 (Scheme 4) [29][30][31]. Starting with a photochemical [2 + 2] cycloaddition between 2-cyclohexen-1-one (37) and

• aldehyde 67 in six steps in 34% yield. After saponification of the ester functionality, treatment with tosyl chloride and trimethylamine resulted in the formation of a ketene that underwent a diastereoselective intramolecular [2 + 2] cycloaddition to provide bicyclic ketone 69. Addition of TMS cerium

• + 2] cycloaddition (Scheme 12) [60]. The synthetic route commenced with known aldehyde 119 which was converted to triol 120 in five steps (Scheme 13). The introduction of the benzyl ether next to the alkyne moiety was necessary to control the stereochemical outcome of the key annulation, and further

Evidencing an inner-sphere mechanism for NHC-Au(I)-catalyzed carbene-transfer reactions from ethyl diazoacetate

• Manuel R. Fructos,
• Juan Urbano,
• M. Mar Díaz-Requejo and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2015, 11, 2254–2260, doi:10.3762/bjoc.11.245

• skeletal rearrangement of the [2 + 2] cycloaddition of 1,6-enynes [4] is shown in Scheme 1, where three different gold–carbene intermediates are involved in the possible transformations. A different reaction in which the formation of gold–carbene intermediates has been proposed arises from the interaction

• relative substrate:catalyst ratio, at a constant catalyst value. Bottom: Plots of kobs vs substrate concentration showing a direct correlation between both magnitudes. The experimental device for the measurement of N2 evolution. The Au(I)-catalyzed skeletal rearrangement of the [2 + 2] cycloaddition of 1,6

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

• accomplished in a one-pot reaction under Wolff–Kishner reaction conditions to generate 223 and 259, respectively (Scheme 41). Cycloaddition reactions [2 + 2] Cycloaddition: Roemer and Lentz [175] have reported the synthesis of fluorinated ferrocenophanes from 1,10-bis(trifluorovinyl)ferrocene and 1,4-(1,10

• -ferrocenediyl)-1,1,2,2,3,3,4-heptafluorobutane. The authors have reported a [2 + 2] cycloaddition reaction under thermal conditions. 1,10-Bis(trifluorovinyl)ferrocene (261) was synthesized starting with diiodoferrocene 260 by Negishi-type coupling. Compound 261 was subjected to a [2 + 2] cycloaddition sequence

• the application of a [2 + 2 + 2] cycloaddition sequence (Scheme 45). To this end, [2 + 2 + 2] cycloaddition of 1,10-diyne 274 was carried out with methyl propiolate (275) in the presence of a cationic rhodium(I)-(S)-BINAP complex (10 mol %) as a catalyst. The desired [2 + 2 + 2] cycloaddition was

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• distance between two double bonds that successfully undergo a [2 + 2] cycloaddition (between 3.5 and 4 Å, the so-called “topochemical reaction control”). Furthermore, in derivatives 2 two adjacent polyolefin chains are orthogonal to each other, because of the steric bulk of the tert-butyl moieties. The p

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• organizing the multivalency of sugar ligands. We planned for a divalent system to start with, in which the dynamics of two at first flexible branches can be controlled by an intramolecular [2 + 2] cycloaddition reaction (Figure 1A). In order to control the [2 + 2] cycloaddition process, it was planned to

• install both branches on a carbohydrate scaffold. This would allow to favour the intramolecular [2 + 2] cycloaddition over an intermolecular reaction and moreover, a multifunctional carbohydrate scaffold facilitates further ligation or immobilization, respectively, of the final molecular construct. After

Enhancing the reactivity of 1,2-diphospholes in cycloaddition reactions

• Almaz Zagidullin,
• Vasili Miluykov,
• Elena Oshchepkova,
• Artem Tufatullin,
• Olga Kataeva and
• Oleg Sinyashin

Beilstein J. Org. Chem. 2015, 11, 169–173, doi:10.3762/bjoc.11.17

• dimerization was observed only upon heating to 190 °C leading to the product of the [2 + 2] cycloaddition reaction [9]. At the same time, 3,4,5-tri(p-fluorophenyl)-1-ethyl-1,2-diphosphole (1e) is stable at room temperature and undergoes the [4 + 2] cycloaddition reaction only upon heating at 60 °C resulting in

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• result of intermolecular [2 + 2] cycloaddition. The photochemical reactivity of these three compounds, which differ from each other by the length and structure of the linker unit, varies considerably. In Figure 8 the photochemical decay curves of 32b, 33a and 39 as well as the irradiation UV spectrum of

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• palladium nanoparticles, that were generated in situ in water with the elimination of acetone. One of the major issues is the preparation of polysubstituted phenanthridines, in particular asymmetrically positioned on one of phenyl side-rings. An intriguing approach over rhodium-catalysed alkyne [2 + 2 + 2

• ] cycloaddition reaction [36] (Scheme 15) offered a highly efficient method with excellent regioselectivity (in case of bulky groups), with additional advantage of the C-6 fluorinated methyl substituent – promising for PET probe development. Most of the metal catalysts employed for phenanthridine synthesis are

Design and synthesis of novel bis-annulated caged polycycles via ring-closing metathesis: pushpakenediol

• Sambasivarao Kotha and
• Mirtunjay Kumar Dipak

Beilstein J. Org. Chem. 2014, 10, 2664–2670, doi:10.3762/bjoc.10.280

• ) [27] were assembled by employing various novel synthetic routes. Results and Discussion In connection with our interest to prepare annulated PCUD, we proposed various dialkylated pentacyclic diones such as 1,9-dialkylpentacyclo[5.4.0.02,6.03,10.05,9]undeca-8,11-dione 12 by using [4 + 2] and [2 + 2

• ] cycloaddition strategies, which involve the DA reaction of 2,5-dialkyl-1,4-benzoquinone 10 and 1,3-cyclopentadiene (9) followed by the formation of the cyclobutane ring through a [2 + 2] photocycloaddition reaction (Figure 2). Later on, one can introduce two allyl groups by using traditional carbonyl chemistry

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• -Dieckmann condensation. Palladium-catalyzed oxidative arylation. Tandem cross-coupling/Dieckmann condensation. Rhodium-catalyzed double [2 + 2 + 2] cycloaddition. Silver oxide-mediated alkyne–arene annulation. Silver acetate-mediated alkyne–arene annulation. Cyclization through phosphinylation/alkylation of

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• - [31], elastase- [32][33][34][35], and HIV-1 protease [36] and papain [37]. For the design of β-lactams, the Staudinger reaction involving a [2 + 2] cycloaddition of ketenes and imines is the most common method used [38]. However, Ugi reactions starting form β-amino acids are also described. In 2002

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

Triphenylene discotic liquid crystal trimers synthesized by Co₂(CO)₈-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

• Bin Han,
• Ping Hu,
• Bi-Qin Wang,
• Carl Redshaw and
• Ke-Qing Zhao

Beilstein J. Org. Chem. 2013, 9, 2852–2861, doi:10.3762/bjoc.9.321

• trimers using Co2(CO)8-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition reaction is reported. The trimers consist of three triphenylene discotic units linked to a central 1,2,4-trisubstituted benzene ring via flexible spacers. The trimers were synthesized in the yields up to 70% by mixing the monomers

• synthesis of discotic oligomers [46][47][48][49][50]. The transition metal-catalyzed [2 + 2 + 2] cycloaddition of three alkynes for the synthesis of polysubstituted benzene derivatives was studied due to its high efficiency and atomic efficiency [51]. The use of Co2(CO)8 as a catalyst has been extensively

• applied to the synthesis of hexabenzocoronene DLCs through diarylethyne cyclotrimerization [51]. In this paper, we report four star-shaped DLC trimers with triphenylene discotic units by using a Co2(CO)8-catalyzed terminal alkynes [2 + 2 + 2] cycloaddition, and the trimers exhibit ordered rectangular

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• /AgClO4] (5/15 mol %) furnished corresponding functionalized pyrrolidines in good yields and moderate stereoselectivity (Scheme 22) [58]. The preferred alkene activation versus allenes was recently observed in the cascade 1,3-migration/[2 + 2] cycloaddition of 1,7-enyne benzoates (Scheme 23) [59]. When 83

• with simple ketones. Proposed reaction mechanism for the intramolecular [Au(I)]-catalyzed hydroalkylation of alkenes with ketones. Tandem Michael addition/hydroalkylation catalyzed by [Au(I)] and [Ag(I)] salts. Intramolecular [Au(I)]-catalyzed tandem migration/[2 + 2] cycloaddition of 1,7-enyne

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• last years to the development of enantioselective versions of these processes by using chiral gold catalysts. In this section, we highlight the most important developments in this area. In 2007, Toste and coworkers described an intramolecular [2 + 2] cycloaddition of allenenes by using gold catalysts

• catalyst provides a gold–allyl cationic species of type IX, which is the species undergoing the cycloaddition process with the diene [73]. Simple alkenes do also react with gold-activated allenamides to provide cyclobutane products, formally resulting from a [2 + 2] cycloaddition. Thus, independent

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• in 88% overall yield (over two steps). Another approach to non-linear systems utilizes a cobalt-mediated intramolecular [2 + 2 + 2]-cycloaddition of a triyne system 9 leading to the fourfold annulated ring system 10 in only one step [16]. Late stage functionalization led to the anticipated structural

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

• Sylvestre Bachollet,
• Kimitada Terao,
• Shin Aida,
• Yasuhiro Nishiyama,
• Kiyomi Kakiuchi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2013, 9, 2015–2021, doi:10.3762/bjoc.9.237

• (---) vs the pathlength in the microcapillary (···). General [2 + 2]-cycloaddition of furanones with alkenes. [2 + 2]-Cycloadditions of furanone 1 with cyclopentene (2). [2 + 2]-Cycloadditions of furanone 1 with 2,3-dimethylbut-2-ene (4). Experimental results for the cycloaddition of 1 with 2. Experimental

Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

• Jungho Jun,
• Hyu-Suk Yeom,
• Jun-Hyun An and
• Seunghoon Shin

Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198

• + 2] cycloaddition [4][5] where JohnPhos ligand showed the best performance, the optimal ligand for the current carboalkoxylation was different. While the role of electron density of the ligand was less obvious, the steric bulk on the ligand clearly seemed to retard the reaction and a less bulky PPh3

• = di-t-butyl-o-biphenylphosphine, JohnPhos) formed in situ was used as catalyst, the reaction was more efficient in chlorinated solvents rather than polar aprotic or aromatic hydrocarbon solvents (Table 1, entries 1–7). Contrary to the previous [4 + 2] cycloaddition, formal enyne cross metathesis or [2

Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• a mechanism for caryolene formation that involves a concerted but asynchronous [2 + 2] cycloaddition, deprotonation by an enzyme active-site base (as yet, with identity unknown [55][58][59][60][61][62][63][64]), and concerted but asynchronous reprotonation/cyclization (Scheme 2, right). However

Polar reactions of acyclic conjugated bisallenes

• Reiner Stamm and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 36–48, doi:10.3762/bjoc.9.5

• and epoxides, hydrohalogenation (HCl, HBr addition), halogenation (Br2 and I2 addition), and [2 + 2] cycloaddition with chlorosulfonyl isocyanate. The resulting adducts were fully characterized by spectroscopic and analytical methods; they constitute interesting substrates for further organic

• conjugated dihalodienes and trienes. Finally, the reaction of 2 with chlorosulfonyl isocyanate provides a β-lactam derivative formed in a formal [2 + 2] cycloaddition via a zwitterionic intermediate. Taken together, these studies show that conjugated bisallenes [39], which are readily available by high

• intramolecular chlorine shift from its resonance structure 73 to provide the sulfenimide intermediate 74. Hydrolysis of the latter then provides product 75. In another heterocumulene addition Skattebøl and Boanhave studied the addition of dichloroketene and diphenylketene to 2 [38]. In both cases [2 + 2

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• santonin. It is generally regarded that the systematic and ground-breaking investigations of Ciamician and Silber [3] paved the way for modern synthetic photochemistry. At the turn of the 20th century they described the first examples of now common reactions such as intramolecular [2 + 2] cycloaddition

• quantities of materials without the need for particularly specialist equipment. By using an inexpensive peristaltic pump, the [2 + 2] cycloaddition of maleimide (76) and n-hexyne was run continuously for 24 hours under optimised conditions for a custom-built Pyrex reactor (Scheme 25). This reaction produced

• product and recycling of the solution. A gas-liquid slug flow was also recently used for the [2 + 2] cycloaddition of a chiral cyclohexenone 89 with ethylene (Scheme 30) [83]. The reactor comprised of FEP tubing (1.0 mm i.d.) wrapped around a quartz immersion well with nine windings. The reaction was

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• product (Scheme 41), the reaction of 24 with either dichloro (170: R = Cl) or diphenylketene (170, R = phenyl) furnished largely the [2 + 2] cycloadducts 171. Only traces of the Diels–Alder adduct 172 are observed in this case. This example seems to be the only one in which the [2 + 4] and [2 + 2

• ] cycloaddition mode compete [123]. Occasionally highly alkylated bisallenes such as 24 also provide ene-addition products. If the double-bond dienophile is replaced by an activated triple-bond dienophile 173, another course of events is observed (Scheme 42) [21][124][125][126]. In this case the Diels–Alder step

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

•  5) [38]. This reaction is important for the hydroamination of alkynes by Cp2ZrX2 complexes, which proceeds through zirconium imido intermediates [39]. A similar [2 + 2] cycloaddition of symmetrical alkynes across a tungsten nitride is the initial step in Johnson's nitrile-alkyne cross metathesis

• silylenes [54][55], insertion of olefins into hydrosilylenes [56], and bimolecular redistribution of thiolates between ruthenium silyl and silylene complexes [57]. Reactivity that involves metal-ligand cooperation (in the sense described in this article) has been reported in the formal [2 + 2] cycloaddition

• ) imide [42]. Formal [2 + 2] cycloaddition of methyl isocyanate at a ruthenium silylene [58]. Oxygen-atom transfer from phenyl isocyanate to a cationic terminal borylene [60]. Coupling of a phosphorus ylide with an iridium methylene [62]. Reactions of (PNP)Ir═C(H)Ot-Bu with oxygen-containing

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• Tantillo [6] regarding the thermal [2 + 2] cycloaddition reaction suggest that the energy barrier for this reaction should not be effected by the presence of two radical stabilizing groups over one, it was postulated that this cycloaddition process was facilitated by exposure to incident light [7]. Thus

• , the mixtures of compounds 2 and 9 were reconstituted in CH2Cl2 and placed in front of two 6 W UV lamps for 16 h at rt to afford the desired cyclobutenes (Method B, Table 2, entries 5–8). During optimization of the conditions for the [2 + 2] cycloaddition reaction (Method A), it was found that reducing

• not be identified (see spectral data in Supporting Information File 1). Aryl-substituted alkynones 9{1,5}–9{1,8} were not available for the molybdenum-mediated cyclocarbonylation process due to competing [2 + 2] cycloaddition reactions (Table 2). The majority of these β-carboline-containing products

Facile isomerization of silyl enol ethers catalyzed by triflic imide and its application to one-pot isomerization–(2 + 2) cycloaddition

• Kazato Inanaga,
• Yu Ogawa,
• Yuuki Nagamoto,
• Akihiro Daigaku,
• Hidetoshi Tokuyama,
• Yoshiji Takemoto and
• Kiyosei Takasu

Beilstein J. Org. Chem. 2012, 8, 658–661, doi:10.3762/bjoc.8.73

• , Japan 10.3762/bjoc.8.73 Abstract A triflic imide (Tf2NH) catalyzed isomerization of kinetically favourable silyl enol ethers into thermodynamically stable ones was developed. We also demonstrated a one-pot catalytic reaction consisting of (2 + 2) cycloaddition and isomerization. In the reaction

• procedure would be required. In this communication, we describe isomerization of silyl enol ethers by an organocatalyst under mild conditions and its application to a one-pot catalytic reaction involving isomerization of silyl enol ethers and (2 + 2) cycloaddition. Results and Discussion During our research

• ) cycloaddition of silyl enol ethers with acrylates generating substituted cyclobutanes [10]. We are intrigued that the isomerization of silyl enol ethers and successive (2 + 2) cycloaddition could be promoted by Tf2NH in a one-pot reaction. When 1a was treated with Tf2NH (1 mol %) under the isomerization