Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• reaction requires a reduction of palladium(II) back to palladium(0) which is apparently achieved by the present triethylamine. Keywords: 1,2-addition; aryl iodides; ketones; nucleophilic addition; palladium catalysis; Introduction For our systematic studies on samarium diiodide promoted cyclizations

• lower and higher homologs. With cycloheptanone derivatives 5a/b less efficient cyclizations were observed. The mixture of diastereomers 5a/5b (ca. 1:1) provided a mixture of compounds containing the two isomers 15a and 15b, from which pure 15a could be isolated (Scheme 6). A diastereomerically enriched

• -substituted ketone 2 to compounds 8, 9 and 10. Palladium-catalyzed cyclization of diastereomeric cyclopentanone derivatives 3a/3b to products 11a and 11b and synthesis of p-nitrobenzoate 12a. Palladium-catalyzed cyclizations of diastereomeric cyclohexanone derivatives 4a and 4b leading stereoselectively to

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• formed. Instead, we isolated the trisubstituted oxazole derivative 6 in 55% yield. The scope of this reaction has not been studied by us, however it is known in the literature that enamides can undergo related oxidative cyclizations to oxazoles in the presence of the reagent cocktail employed or under

• -ketoenamines 2c–e and of β-ketoenamides 3c–h. Synthesis of α-methoxy-β-ketoenamine 2i, its N-acylation to 3i and the reaction of β-ketoenamide 3a with iodosylbenzene to 5-acetyloxazole 6. Cyclizations of β-ketoenamide 3i leading to 2,2´-bipyridine derivative 4i or to the related 2-(2-pyridyl)pyrimidine 7 or

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• ]. Carreira et al. have developed a ring expansion of 3-oxetanone to synthesize substituted piperazines [18]. Transition metal (such as Ti, Au, and Pd) catalyzed cyclizations of linear starting materials have been used by several groups including the Schafer, Nelson, Huang, and Wolfe groups to synthesize

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• ), and of derivatives (by post-PKS reactions) is shown in Figure 18. The authors suggested that seven malonyl-CoA building blocks are connected via Claisen-condensation reactions, followed by aldol-type cyclizations between C-2 and C-7, as well as between C-8 and C-13. The subsequent lactonization yields

Study on the synthesis of the cyclopenta[f]indole core of raputindole A

• Nils Marsch,
• Mario Kock and
• Thomas Lindel

Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36

• were 6-hydroxyallylated indolines which gave good yields of cyclopenta[f]indolines after treatment with SnCl4, as soon as sterically demanding β-cyclocitral adducts were reacted. Most successful were Pt(II) and Au(I)-catalyzed cyclizations of N-TIPS-protected indolin-6-yl-substituted propargylacetates

• reaction [34]. By installation of a triflyloxy group in the indole 5-position, Pd-catalyzed cyclization also would become possible. As an alternative to the cyclization of enones, Lewis acid-induced cyclizations of allylic alcohols could afford the desired cyclopenta[f]indole system (C, D). Here, it was

• ketone 26 proceeded in the highest yield of all our Meyer–Schuster rearrangements. With triflated α,β-unsaturated ketone 26 in hand, we attempted reductive Heck cyclizations to the raputindole core structure. For instance, we employed Pd(dba)2 (12 mol %), QPhos (24 mol %), and NEt3 (1.20 equiv) in DMF at

Solving the puzzling competition of the thermal C²–C⁶ vs Myers–Saito cyclization of enyne-carbodiimides

• Anup Rana,
• Mehmet Emin Cinar,
• Debabrata Samanta and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 43–49, doi:10.3762/bjoc.12.6

• pathway if the trapping reaction by hydrogen transfer is no more rate determining. Keywords: DFT computation; diradical; enyne-carbodiimides; hydrogen transfer; thermal cyclization; Introduction The thermal cyclizations of enediynes [1][2][3][4][5][6], enediallenes [7][8][9][10], bisallenes [11], enyne

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• cell death [4]. The natural chromene rhodomyrtone (Figure 1) is known to exhibit potent antibacterial activity [5]. As a consequence, a number of methods have been developed for the synthesis of substituted 4H-chromenes [6]. This includes, inter alia, transition metal-mediated cyclizations [7

Synthesis of cyclic N¹-pentylinosine phosphate, a new structurally reduced cADPR analogue with calcium-mobilizing activity on PC12 cells

• Ahmed Mahal,
• Stefano D’Errico,
• Nicola Borbone,
• Brunella Pinto,
• Agnese Secondo,
• Valeria Costantino,
• Valentina Tedeschi,
• Giorgia Oliviero,
• Vincenzo Piccialli and
• Gennaro Piccialli

Beilstein J. Org. Chem. 2015, 11, 2689–2695, doi:10.3762/bjoc.11.289

• diluted conditions. In our opinion, the target intramolecular cyclizations failed because of the poor mobility of the 5’-OH ribose function, as well as because of the unfavourable anti conformation of the N-glycosidic bond induced by the presence at the N1 position of the purine base of the bulky ω

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• rearrangements and cyclizations experimentally. The structure elucidation of terpenoids can be challenging because of the multicyclic carbon skeletons with several contiguous stereocenters. The assistance of 13C labels can in such cases be especially helpful, and if completely 13C-labeled carbon backbones can be

• interesting insights into terpene synthase catalyzed cyclizations. Labeled oligoprenyl diphosphates, the substrates for these enzymes, can be made available by synthesis and provide an excellent tool for such investigations, as recently demonstrated for sesquiterpenes by the synthesis of all 15 singly 13C

• are in line with the proposed cyclization mechanism starting from geranylfarnesyl diphosphate (GFPP, 53), which undergoes two cyclizations yielding cation 54. A 1,5-hydride shift at C-12 to C-19 leads to the allylic cation 55. Additional ring closure fuses the tricyclic system 56, which rearranges to

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• Hanmo Zhang E. Ben Hay Stephen J. Geib Dennis P. Curran Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA 10.3762/bjoc.11.181 Abstract Two new fates of imine intermediates formed on radical cyclizations of ene-sulfonamides have been identified, reduction and hydration

• /fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3

• ; radical cyclization; radical fragmentation; spiro-indoles; Introduction Radical additions and cyclizations of ene-sulfonamides are useful reactions in a number of settings. The primary products of these reactions, α-sulfonamidoyl radicals, are often thought to undergo elimination reactions of sulfonyl

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