Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• , cyclic amines were produced. Carboxylic acids were particularly fruitful affording C-centered radicals that alkylated alkenes and took part in tandem addition cyclizations producing chromenopyrroles; decarboxylative homo-dimerizations were also observed. Acceptors initially yielding radical anions

• included nitroaromatics and aromatic iodides. The latter led to hydrodehalogenations and cyclizations with suitable precursors. Reductive SCPC also enabled electron-deficient alkenes and aromatic aldehydes to be hydrogenated without the need for hydrogen gas. Keywords: carboxylic acids; free radicals

• methods could be enlisted in constructive molecular assembly applications. Our study of SCPC processes revealed that a wide range of carboxylic acids could be deployed in preparatively useful ways. Radical additions to alkenes, cyclizations and tandem addition–cyclizations, as well as homo-couplings, were

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

• also that boat-like conformations are preferred over chair-like ones. These studies accurately correlated with the experimental results observed in these types of cyclizations [32][33][34]. The preference of the boat-like transition state was ascribed to the co-planarity of the carbonyl group during

Azirinium ylides from α-diazoketones and 2H-azirines on the route to 2H-1,4-oxazines: three-membered ring opening vs 1,5-cyclization

• Nikolai V. Rostovskii,
• Mikhail S. Novikov,
• Alexander F. Khlebnikov,
• Galina L. Starova and
• Margarita S. Avdontseva

Beilstein J. Org. Chem. 2015, 11, 302–312, doi:10.3762/bjoc.11.35

• derivatives were reported [27][28][29]. As also known, the azomethine ylide derived from N-benzylideneanisidine and diazoacetylacetone under Rh2(OAc)4-catalysis undergoes 1,3-cyclization to an aziridine derivative in high yield, rather than 1,5-cyclization [22]. However, no cyclizations of azirinium ylides

• azirenooxazole 10j to azirinium ylide 9j. The cyclizations of betaines 14j,14′j into bicycles 6j,7j proceed with extremely low activation barriers (1.1 and 4.7 kcal/mol). The alternative pathway to compounds 6j,7j, involving reversible formation of carbonyl ylide 15j, can result in exclusive formation of [3.2.1

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• chloride via the intermediate formation of a methanesulfonothioate unit in 7a or 7b, from which the methylsulfonyl group departs after a nucleophilic attack from the adjacent N-center (cyclization-IIa) or S-center (cyclization-IIb). While in such multistep cyclizations the elucidation of the full mechanism

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• hypervalent iodine reagents [9][10][11][12], and homogeneously or heterogeneously catalyzed multicomponent reactions [13][14]. Moreover, radical cyclizations predominantly conducted using Bu3SnH in the presence of azobisisobutyronitrile (AIBN) play a crucial role [15][16]. However, all these methods require

• . Intermolecular cyclizations generally fall into two further categories. In the first scenario, an anodically generated nucleophile (cathodically generated electrophile) reacts with an electrophile (nucleophile) present in solution. Consequently, an intermediate is formed, which undergoes ring-closure reaction

• Michael addition/ring closure with in situ generated quinones (section 2.2) and sequential cyclizations involving acyliminium species and alkoxycarbenium ions (section 2.3) represent the majority of recently reported intermolecular electrochemical cyclizations. Cases which do not fall into any of these

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• derivative afforded three condensed O,N-heterocycles containing tetrahydro-1,4-benzoxazepine and tetrahydroquinoline moieties. trans-Diastereoselectivity of the cyclizations was determined by the correlation of 3JH,H coupling constants with the geometry of the computed conformers, while (2R,15aR) absolute

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• synthetic procedure involves an addition/elimination protocol of selenium derivatives, the formation of isomeric endo-exo-dienes 2, 3 and 5, 6 resembles the zig-zag cyclizations of nonconjugated cyclic diynes of medium ring size reported by Gleiter [31][32]. In order to check the limits of these selenium

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• range of N-diphenylphosphinoyl aromatic imines underwent cyclizations (Scheme 33) with an allenoate in toluene at −25 °C for 48 h, affording dihydropyrrole derivatives in 68–90% yield and excellent ee (94–98%). The catalytic amounts of triethylamine and water significantly increased the reaction rates

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• with classical organic acylation reactions (Friedel–Crafts reaction, esterification, amide synthesis, Scheme 1). Some of these complexes have been used as organometallic gelators [19][20], as a novel class of cytostatic compounds [26], and catalysts for unusual radical cyclizations [27][28][29][30][31

• ] cyclizations [56][57][58]. Carboxylates employed as titanocene starting materials for azide-substituted complexes. Azides employed in this study and conditions for their synthesis. Most active titanocenes of this study and their AC50 values. Modular titanocene synthesis via acylation reactions [24]. Synthesis

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• (Heck-type cyclization), unfortunately, were unsuccessful. Heck-type cyclizations work nicely with planar PAHs and even on moderately curved PAHs, such as corannulene [15][23][24]. Nonetheless, when applied to the indenocircumtrindene synthesis, the reaction did not give any ring-closed products

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

• before a follow-up cyclization event can take place. An example of this is the use of N-Boc protected amino acids in the Ugi reaction. Subsequent deprotection of the linear Ugi-product allows cyclization and reactions of this type are classified as Ugi Deprotection–Cyclizations (UDC, Scheme 4). Moreover

• , cyclizations can also be initiated by activation of the Ugi-product via an Ugi Activation–Cyclization procedure and involves the use of convertible isocyanides as Ugi-substrates. An example of a convertible isonitrile is Armstrong’s isocyanide which can be cleaved after acidic treatment (Scheme 5). A

• disadvantage that cyclization of the linear dipeptide unit is difficult. Instead of relatively easy ester cyclizations, the Ugi-product contains a C-terminal amide that is more difficult to cyclize. Therefore, Ugi MCRs towards diketopiperazines require subsequent post-condensation modifications such as Ugi

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• nitriles is retained during this reaction [40]. In the present report we describe our efforts to further broaden the substrate scope of this multicomponent reaction and the subsequent cyclizations by employing aromatic dicarboxylic acids. This extension should allow a rapid access to fairly complex

• -methoxy-β-ketoenamides). With these products of a multicomponent reaction we performed cyclizations to rapidly construct symmetrically and unsymmetrically substituted pyridine and pyrimidine derivatives. Hence a very short approach to fairly complex functionalized oligoaromatic systems was established. In

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• derivatives. Keywords: benzoxazepines; diversity-oriented synthesis; multicomponent reactions; Mitsunobu reaction; Ugi reaction; Introduction Although the classical Ugi 4-component reaction (U-4CR) leads to acyclic peptide-like compounds, post-condensation cyclizations can afford a huge variety of drug-like

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• -exo-dig fashion. Radical quenching gave cis-arylvinylcyclopropane 238. Arylvinylcyclopropane rearrangement was followed by rearomatization to give tetracycle 239 (see Scheme 29). Padwa and coworkers [201] discovered an intermediate DVCPR during their investigation of rhodium-catalyzed cyclizations of

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

• synthesized in a similar way starting with the peroxidation of 2-methyl-2-(3-methylbut-3-enyl)oxetane (222), followed by oxetane-ring opening in triethyl(2-methyl-4-(2-methyloxetan-2-yl)butan-2-ylperoxy)silane (223) (Scheme 63) [250]. Dioxanes can also be synthesized by inramolecular cyclizations with the

• acetate-catalyzed synthesis of cyclic peroxides [336]. 3.10. Acid-mediated cyclizations of peroxides The intramolecular cyclization of unsaturated peroxyacetals 273a–d in the presence of TiCl4 or SnCl4 occurs via formation of peroxycarbenium ions to give methoxy- and chlorine-containing dioxanes 274a–d as

The renaissance of organic radical chemistry – deja vu all over again

• Corey R. J. Stephenson,
• Armido Studer and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 2778–2780, doi:10.3762/bjoc.9.312

• of organic radical chemistry that delivered groundbreaking results, especially in organic synthesis. By the 1990’s, radical reactions (especially cyclizations) were broadly recognized as powerful tools to make molecules. This Renaissance I in organic radical chemistry was built on prior renaissances

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• with Red-Al. Both isomers B and C can also be directly accessed from 1 with the corresponding cis- and trans-vinyl nucleophiles. Allylic alcohol B can be used as an intermediate in the synthesis of various natural products or intermediates thereof. The cis-double bond allows cyclizations to five- or

Gold(I)-catalyzed domino cyclization for the synthesis of polyaromatic heterocycles

• Mathieu Morin,
• Patrick Levesque and
• Louis Barriault

Beilstein J. Org. Chem. 2013, 9, 2625–2628, doi:10.3762/bjoc.9.297

• cyclizations of the enol ether 11a (R1 = p-BrC6H4, R2 = H) gave the corresponding benzothiophene 12a in 83% yield. The use of electron-poor silyl enol ether 11b (R1 = p-NO2C6H4, R2 = H) gave the desired product 12b, albeit in lower yield of 63%. Di- and trisubstituted silyl enol ethers 11c (R1 and R2 = H) and

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

• , aldol reactions, 1,3-dipolar cycloadditions, and cyclizations [13][14][15]. Other gold-promoted asymmetric induction strategies rely on the use of chiral counterions. Indeed, it has been shown that a tight chiral ion pair with the gold cation is able to induce excellent levels of asymmetry in certain

• cyclizations [16]. Cycloaddition reactions are very important synthetic processes that allow the transformation of simple acyclic precursors into complex cyclic or polycyclic adducts in a rapid and efficient way [17][18], usually providing a rapid increase in skeletal and stereochemical complexity. Moreover

Gold(I)-catalyzed formation of furans from γ-acyloxyalkynyl ketones

• Marie Hoffmann,
• Solène Miaskiewicz,
• Jean-Marc Weibel,
• Patrick Pale and
• Aurélien Blanc

Beilstein J. Org. Chem. 2013, 9, 1774–1780, doi:10.3762/bjoc.9.206

• construct the furan motif [4][5]. Among them, late transition metal-catalyzed intra- or intermolecular cyclizations of oxygenated functionalities on unsaturated carbon–carbon bonds proved to be powerful synthetic methods due to their mildness, efficiency and diversity [6][7]. In the last decade, gold

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• intermediates I encourages us to understand their behavior in the absence of a dipolarophile. This work reports gold-catalyzed intramolecular cyclizations of these allenyl acetals [19]. Results and Discussion We first tested the intramolecular cyclizations of allenyl acetal 1a with PPh3AuCl/AgSbF6 (5 mol

• highlights the diversified mechanism of such oxidative cyclizations. We prepared the additional substrates 5b–5g bearing an acetate group to examine the scope of the reaction, results are shown in Table 3. This gold-catalyzed cyclization was applicable to compound 5b bearing a cyclopentyl bridge, giving the

Anodic coupling of carboxylic acids to electron-rich double bonds: A surprising non-Kolbe pathway to lactones

• Robert J. Perkins,
• Hai-Chao Xu,
• John M. Campbell and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2013, 9, 1630–1636, doi:10.3762/bjoc.9.186

• form product 9. No product from sulfonamide trapping (8) was observed. However, when the reaction was run under more basic conditions (0.5 equivalents of lithium methoxide) cyclic voltammetry data indicated that the oxidative cyclizations were initiated by the oxidation of sulfonamide anion. This led

• to initial formation of N-localized radical 6. Depending on the reaction conditions, the experiment favoured either a sulfonamide or alcohol based cyclization. Density functional theory (DFT) calculations suggested that sulfonamide based cyclizations proceed by addition of the N-localized radical to

• the ketene dithioacetal in the absence of a trapping group [21]. The anodic coupling of a carboxylic acid group with a vinyl sulfide and an enol ether were also examined (Table 2). As with earlier alcohol and amine based cyclizations, reactions with the vinyl sulfide coupling partner proceeded much

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• the addition is about as fast as the 6-endo cyclization of the hexenyl radical. Such reactions and other even slower cyclizations are well documented in titanocene mediated and catalyzed radical processes [61][62][63][64][65][66][67][68][69]. Therefore, the relatively high computational rate constant