Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• traditional Pd-catalyzed aryl–heteroaryl coupling to biaryls [57]. Since then, KOt-Bu has been used as a mediator for various reactions including aryl–aryl coupling [58][59][60][61][62][63], inter- and intramolecular cyclizations [64][65][66][67][68], amidation [69], alkenylation [70], oxidation [71] and

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• , sultams have been prepared employing Diels–Alder reactions, radical cyclizations, reductions of sulfonylimines, ring-closing metatheses, nucleophilic aromatic substitutions and Heck cyclizations [14][15][16]. Earlier on, our group has developed versatile syntheses of sultams based on the transformation of

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• conditions to effect catalytic processes with sub-stoichiometric quantities of iodine compound in the presence of an oxidant [6][7][8][9][10][11]. In this regard, we have reported the use of iodoarenes as precatalysts in the cyclizations of N-alkenylamides 1 [12], δ-alkynyl β-ketoesters 2 [13] and 5-oxo-5

• -phenylpentanoic acid (3, Scheme 1a–c) [14]. These three cyclizations exemplify three different proposed reaction pathways, i.e., iodine(III) activation of alkenes, alkynes and ketones. These cyclizations can be rendered enantioselective by the generation of non-racemic chiral iodine(III) species from chiral

• attack by the amide and release of the iodoarene (Scheme 7). These two cyclizations are complementary, however, the reaction with β-amidoketones exhibits a superior substrate scope. In addition, the use of a chiral iodoarene should lead to enantioselective cyclizations of β-amidoketones; this is not

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• that use SelectfluorTM (8) as a simple and highly reactive electrophilic F-transfer reagent. Besides fluoro-cyclizations of olefines [56], also the asymmetric α-fluorination of prochiral carbonyl compounds or analogues like enamides 7 has been carried out with remarkable enantioselectivities by using

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• . There are literature reports about similar transition-metal-catalyzed cyclizations of o-alkynylphenols to construct benzofurans [34][35]. These heterocycles are important structural units in a variety of biologically active natural or synthetic compounds [36][37]. Full hydrogenation of the 2- or 4

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• -based MCRs as the Ugi four-component reaction (Ugi-4CR) and the Groebke–Blackburn–Bienaymé reaction (GBB-3CR) in combination with post-cyclizations are powerful tools to access diversity as well as complexity in a one-pot procedure; in this way they largely cover the available chemical space [9][10][11

• cyclizations [69][70]. There are examples of using aminoazoles as an amine component in GBB-3CR (Scheme 1). They mostly involve different substituted 3-amino-1,2,4-triazoles [71][72][73][74][75] and 2-amino(benzo)thiazoles [71][72][76][77][78][79][80][81][82][83][84][85][86][87][88]. Several publications deal

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• reactions to alkynyl selenides in the absence of transition metals [16] and the addition of p-toluenesulfonic acid [17] are applied to obtain vinyl organometallic compounds and key selenoester intermediates. Finally, electrophilic cyclizations [18][19] of systems bearing a selenide alkynyl group allow the

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• proposed the mechanism outlined in Scheme 4 for the formation of compounds 12 and 13. The first step is the formation of hydrazide 18. The electronic properties of the substituents designate the fate of the reaction at this step. The intermediate undergoes either 6-endo-dig or 6-exo-dig cyclizations to

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• (Table 2). Some important information of the reactions are listed below: (1) iodine-mediated cyclizations of terminal N-propargylthioureas 55 gave exclusively 4,5-dihydrothiazoles 57 through a 5-exo-dig cyclization, whereas internal N-propargylthioureas 55 under the same reaction conditions gave a

• 4,5-dihydrothiazoles and the competing 6-endo-dig ring-closing process affords 4H-1,3-thiazines after conversion of the charge-transfer complex into the ring-opened iodovinyl B or bridged iodirenium C ions; (2) bromine-mediated cyclizations of both electron-poor and electron-rich N-propargylthioureas

• 55 gave exclusively 4,5-dihydrothiazoles 57 in moderate to good yields; (3) phenyl hypochloroselenoite-mediated cyclizations of terminal N-propargylthioureas 55 underwent a regioselective 5-exo-dig cyclization giving the corresponding 4,5-dihydrothiazoles 57 in moderate yields. On the other hand

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

• demonstrated the greatest resemblance to combretastatin A-4. In 2008, Frontier et al. have examinated the impact of the dienone substitution in Nazarov cyclizations [69]. They synthesized a series of the Nazarov substrates 133 with electron-donating substituents at C-2 and electron-withdrawing substituents at

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• indicated that the two cyclizations of 1a did not happen simultaneously but followed a particular sequence. Further attempts to shorten the reaction time by enhancing the temperature from 120 °C to 140 °C significantly decreased the yield (Table 1, entry 8), on account of decomposition of both the starting

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

• reaction; cf. Scheme 3). In this case the diol and the metal oxide form a glycol ester intermediate which then undergoes an intramolecular oxidative addition to a remote double bond. Thereby, type B oxidative cyclizations converge to the same (or very similar) reactive intermediate as is passed through in

• in Scheme 3). The key intermediate and cyclization precursor may then involve a coordinative bond of that ether oxygen to the strongly Lewis acidic metal center. Due to the close relation to type B cyclizations, they can be classified as type B’ (Scheme 3). Reagents that mediate this type of reaction

• of the present review is to assemble key results of these applications and illustrate scope and limitations. Review Oxidative cyclizations in the synthesis of carbohydrates, amino acids and polyketide natural products (+)-Anhydro-D-glucitol and (+)-D-chitaric acid (+)-Anhydro-D-glucitol (6) was

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

• components. In the presence of these heterocyclic aldehydes, reactions tolerated variations in amine components and led to either isolated N-arylamide Ugi–Smiles adducts or N-arylepoxyisoindolines, products of tandem Ugi–Smiles Diels–Alder cyclizations, in moderate yields. A thienyl-substituted aldehyde was

Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes

• Jimena E. Díaz,
• María C. Mollo and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190

• synthetic methods can be attributed to the intrinsic difficulty of cyclizations leading to seven membered heterocycles. This is a consequence of the high activation energies involved in these reactions, which are also hindered by entropic factors [17][18][19][20][21][22]. In addition to this, due to the

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

• and 1,5-benzodiazepine 95, respectively (Scheme 21). 2.2.7 Isoquinolone-1-phosphonates: From Lewis acid catalyzed 6-endo-dig cyclizations of acetylenic Kabachnik–Fields adducts: A modified Kabachnik–Fields reaction for the synthesis of isoquinoline-1-phosphonate derivatives is the three-component

• reaction of acetylenic aldehydes with various amines and dialkyl phosphonates followed by Lewis acid catalyzed 6-endo-dig cyclizations. Wu et al. reported the one-pot reaction of 2-alkynylbenzaldehydes 96, amines 97, and diethyl phosphonate to afford (2,3-disubstituted-1,2-dihydroisoquinolin-1-yl

• acetylenic aldehydes 102. The Kabachnik–Fields adducts of various carbocyclic acetylenic aldehydes 104 and 105 in the presence of AuBr3, PdCl2, AgOTf, AgNO3 or I+ underwent a 5-exo-dig cyclization to give dialkyl 1H-pyrrol-2-ylphosphonates 106. However, iodine-mediated cyclizations lead to pyrrol-1

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