Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• tested in the asymmetric Friedel–Crafts alkylation of N-methylpyrrole with α,β-unsaturated aldehydes. A variety of substituted enals was investigated to explore the activity of the catalytic system which was also compared with monovalent analogues. The catalyst 4b showed excellent turnover rates and no

• loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. Keywords: Friedel–Crafts; homogeneous catalysis; hyperbranched polyglycerol; imidazolidin-4-one

• support in asymmetric organocatalysis. The use of chiral imidazolidinones in organocatalysis has been extensively reported for a wide range of enantioselective reactions involving α,β-unsaturated aldehydes, such as the Diels–Alder reactions [50], 1,3-dipolar cycloadditions [51] and Friedel–Crafts

TTFs nonsymmetrically fused with alkylthiophenic moieties

• Rafaela A. L. Silva,
• Bruno J. C. Vieira,
• Marta M. Andrade,
• Isabel C. Santos,
• Sandra Rabaça,
• Dulce Belo and
• Manuel Almeida

Beilstein J. Org. Chem. 2015, 11, 628–637, doi:10.3762/bjoc.11.71

• between compounds III and IV, respectively, following a general procedure for non-symmetrically substituted TTFs [13] as first described by Underhill and co-workers [14] (Scheme 2). 5-(tert-Butyl)thieno[2,3-d][1,3]dithiol-2-one (I) was prepared by a low temperature Friedel–Crafts alkylation of 5,6-thieno

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• their profound biological importance, there are different routes reported for their synthesis but the common ones are: nucleophilic substitution of an activated glycosyl donor with organometallic aryl derivatives, cross-coupling of aryls with glycals, Friedel–Crafts arylation at the anomeric centre of

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

•  7). Compounds 30–34 were obtained through Friedel–Crafts acylation of 29 with corresponding acyl chlorides in 55–81% yield. Subsequent alkylation with geranyl bromide gave products 35–39 in moderate yields from 55 to 60%. Finally, p-toluenesulfonic acid (pTSA)-catalyzed cyclization afforded the

• target compounds 40 and 41 in 53 and 65% yield, respectively. The synthesis of the second series is shown in Scheme 8 [59]. Amberlyst 15 efficiently catalyzed the condensation of 1,3,5-trihydroxybenzene (29) with isoprene in 53% yield. The following Friedel–Crafts acylation gave the intermediates 43–46

• inhibited angiogenic processes in various in vitro and in vivo models [82][83]. The typical synthesis of genistein starts from 1,3,5-trihydroxybenzene (29, Scheme 10) [84]. After the Houben–Hoesch reaction or Friedel–Crafts acylation, the cyclization of the resulting hydroxyketone 59 in the presence of BF3

Electrochemical selenium- and iodonium-initiated cyclisation of hydroxy-functionalised 1,4-dienes

• Philipp Röse,
• Steffen Emge,
• Jun-ichi Yoshida and
• Gerhard Hilt

Beilstein J. Org. Chem. 2015, 11, 174–183, doi:10.3762/bjoc.11.18

• the halonium source. Several reactions using bromonium- and iodonium cations such as iodo-etherification, lactonisation or Friedel–Crafts alkylation reactions can be found in literature. However, these procedures often use expensive or toxic halonium sources like molecular bromine [10][28][29] or

Redox active dendronized polystyrenes equipped with peripheral triarylamines

• Toshiki Nokami,
• Naoki Musya,
• Tatsuya Morofuji,
• Keiji Takeda,
• Masahiro Takumi,
• Akihiro Shimizu and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2014, 10, 3097–3103, doi:10.3762/bjoc.10.326

•  2. Di(p-bromophenyl)carbinol (1) was treated with SOCl2 to obtain di(p-bromophenyl)methyl chloride (2) in quantitative yield. A Friedel–Crafts-type alkylation [29] of diphenylsilane 3 with 2 in the presence of boron trifluoride etherate as a Lewis acid gave 4 in 86% yield. The oxidation potential of

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• -acyliminium ion pool and under Friedel–Crafts conditions mono-alkylation products are formed (Scheme 8) [43][44]. A problem with conventional Friedel–Crafts alkylation is the mono-alkylated product is more reactive than the starting material making di- and tri-alkylation products more likely. Improved yields

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

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

• fluoride ion under formation of an S–F bond. Radical 49 is then further oxidized to the corresponding cationic species 50, which undergoes elimination of HF under formation of cationic intermediate 51. Finally, intramolecular trapping by the aromatic ring in a Friedel–Crafts type reaction leads to

Gold(I)-catalysed synthesis of a furan analogue of thiamine pyrophosphate

• Amjid Iqbal,
• El-Habib Sahraoui and
• Finian J. Leeper

Beilstein J. Org. Chem. 2014, 10, 2580–2585, doi:10.3762/bjoc.10.270

• synthesis of a furan-based analogue of thiamine. This analogue was converted to its diphosphate, which is another extremely potent inhibitor of ZmPDC, and could also be functionalised at the 2-position using a Friedel–Crafts acylation. Results and Discussion Synthesis of ThDP analogue 17 The key step in our

• strong inhibitor of ZmPDC with picomolar affinity. Friedel–Crafts acetylation of the furan at C-2 was successful which opens the possibility of synthesising furan analogues of the enzymic reaction intermediates. Structure of thiamine diphosphate (ThDP, 1). Time course inactivation of ZmPDC by various

Superoxide chemistry revisited: synthesis of tetrachloro-substituted methylenenortricyclenes

• Basavaraj M. Budanur and
• Faiz Ahmed Khan

Beilstein J. Org. Chem. 2014, 10, 2531–2538, doi:10.3762/bjoc.10.264

• -di-tert-butyl-4-methylphenol) improved the yields of methylenenortricyclenes. A complete deuterium incorporation was observed in the superoxide-mediated reaction in DMSO-d6. Friedel–Crafts acylation reactions of 3-methylenenorticyclenes yielded 2-propanone-substituted pentachloronorbornenes

• . Keywords: BHT; dehydrohalogenation/rearrangement; Friedel–Crafts acylation; methylenenortricyclene; superoxide ion; Introduction The chemistry of the superoxide ion (O2−·) has been a subject of growing interest because of its presence in all aerobic organisms as a respiratory intermediate [1][2][3][4][5

Scalable synthesis of 5,11-diethynylated indeno[1,2-b]fluorene-6,12-diones and exploration of their solid state packing

• Bradley D. Rose,
• Peter J. Santa Maria,
• Aaron G. Fix,
• Chris L. Vonnegut,
• Lev N. Zakharov,
• Sean R. Parkin and
• Michael M. Haley

Beilstein J. Org. Chem. 2014, 10, 2122–2130, doi:10.3762/bjoc.10.219

• Kitamura gave tetrahalide 12 in good yield on >10 g scale [25]. Suzuki cross-coupling with 12 furnished p-terphenyl 14, followed by oxidation of the methyl groups to produce diacid 15. Intramolecular Friedel–Crafts acylation then afforded 5,11-dibromo-IF-dione 11. The yields for the Sonogashira cross

• . Black lines represent the molecules with circles denoting the centroid. Transannular cyclization route to diethynyl-IF-diones 8. Suzuki/Friedel-Crafts route to diethynyl-IF-diones 8. Diethynyl-IF-diones synthesized and yields for Sonogashira cross-coupling. Electrochemical and optical data for ID-diones

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• with Friedel–Crafts acylation of 1-methoxynaphthalene (11) yielding 1-acetyl-4-methoxynaphthalene (12, 73%). α-Bromination with copper(II) bromide gave 13 (44%) which was converted to the phosphate ester using tetramethylammonium diethyl phosphate in dimethoxyethane (DME) at room temperature to give

• ) and comparison with an independently synthesized sample obtained from Friedel–Crafts alkylation of 1-methoxynaphthalene (11) with methyl bromoacetate and ferric oxide [27]. Quantum yields for disappearance and percentage conversions for 14a are higher than that of 14b as indicated in Table 1. After

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

• compounds 2 we previously prepared precursors such as 5 (easily available by Wittig–Horner reaction of the appropriate bis-formyl cyclophanes) and subjected them to catalytic hydrogenation followed by a double Friedel–Crafts cyclization. However, it appeared to us that a more direct route to these useful

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• (Dha) derivatives under Lewis acid-mediated conditions has been investigated. The formation of 2-substituted tryptophans is proposed to occur through a selective alkylative dearomatization–cyclization followed by C3- to C2-alkyl migration and rearomatization. Keywords: Dehydroalanine; Friedel–Crafts

• indole migration and rearomatization (Scheme 1, path b). Therefore, the aim of this study was to exploit the C3 Friedel–Crafts (FC) alkylation/C3- to C2 alkyl migration sequence for the synthesis of 2-substituted tryptophans [45][46][47][48][49][50]. The known methods for the synthesis of 2-substituted

• species generated in situ after the Dha/Friedel–Crafts-type reaction with indoles. Attempts to carry out the alkylation/migration reaction with 3-benzhydrylindole (1e) were unfruitful (Table 2, entry 5). When 3-(tetrahydronaphthalen-1-yl)indole (1f) was used, a very low conversion to the corresponding 2

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

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• sequence as shown in Scheme 27-ii [82]. Firstly, a Friedel–Crafts reaction produced the para-substituted phenol in 42% yield. Then, the phenol group was transformed in diethyl aryl phosphate with an AT reaction in 99% yield. Finally, the reduction of the phosphate was achieved in 74% yield. Similar

• reaction [102], Michael addition [103], Diels–Alder reaction [104], Friedel–Crafts alkylation [105]) illustrate the use of phosphoramidates as organocatalysts. These phosphoramidates were not synthesized by an AT reaction. Instead, the reaction of an amine with an electrophilic phosphorus species (P–Cl

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• N-aryl-3-hydroxyisoindolinones with diethyl malonate and subsequent hydrolysis, decarboxylation and Friedel–Crafts acylation sequence also result in the formation of isoindolo[2,1-a]quinolones [16][17]. N-aryl-3-hydroxyisoindolinones with an aptly positioned alkene moiety at the ortho position of

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• subjected to an acid-mediated condensation to give the 9,9’-spirobifluorene. Friedel–Crafts acylation with acetyl chloride gave rise to the racemic 2,2’-diketone which was transformed to the racemic diester in a Baeyer–Villiger oxidation. Saponification of the ester functions then afforded (rac)-1. One part

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• Friedel–Crafts acylation of arenes by the acid chloride of 10. This possibility was repudiated, however, because the similar acyl chloride t-Bu2CH–CO–Cl did not acylate benzene [37][38]. Instead, the technique [39] of acylating an aryllithium compound such as 34 by a lithium carboxylate such as 36 to form

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• defined geometry. Introducing a new motif, Shea et al. have synthesized achiral tridentate (thio)phosphorus triamides and assessed their catalytic activity relative to the established (m-(CF3)2-Ph)2thiourea [18]. In the Friedel–Crafts reaction of N-methylindole with β-nitrostyrene and the Baylis–Hillman

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

• formal [4 + 3] cycloaddition [82]. Starting from 4-methoxyphenol (90) Friedel–Crafts acylation and cyclization provided bicycle 91. Wittig olefination furnished benzofuran 92. Diazotransfer using p-ABSA yielded the crucial diazo compound 93, which was used in the following enantioselective

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

• (Scheme 18, DCE, 50 °C) [55]. To be underlined that despite of efficiency, isomerization of the C=C was found competing with the desired Friedel–Crafts-type alkylation under the optimized reaction conditions. Analogously, [Au(III)] catalysis was employed in the intramolecular hydroarylation of olefins. It

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• substituted Grignard reagent 1.26. A Friedel–Crafts type acylation promoted by either triflic acid or polyphosphoric acid (PPA) furnishes the tricyclic structure 1.28 which upon N-demethylation affords clarinex (1.22). One of the top-selling classes of pharmaceuticals containing the pyridine ring are the

• moderate yield the benzoxazine 1.118; via the imine intermediate. This material can then be condensed with diethyl ethoxymethylenemalonate (1.123), and further cyclised via an intramolecular Friedel–Crafts acylation promoted by polyphosphate. Aluminium tribromide assisted demethylation of the pendant

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• also observed in particular cases affording methylenecyclohexene derivatives like VI [14]. On the other hand, 1,6-enynes VII, bearing an aryl substituent at the alkyne, undergo a formal intramolecular [4 + 2] cycloaddition through an initial 5-exo cyclization followed by a Friedel–Crafts-type reaction

• and 4a’, is generated in preference to 3a which would be the expected product derived from a formal [4 + 2] cycloaddition initiated by a 5-exo cyclization followed by a Friedel–Crafts-type process in intermediate 5a or 5a’, as described by Echavarren and co-workers [18][19]. Prompted by this result

• subsequent Friedel–Crafts reaction (Scheme 6). Both compounds were isolated as single stereoisomers with a high overall yield [43]. In this case, the 5-exo pathway was more competitive compared to the result of model substrate 1a, probably due to the Thorpe–Ingold-type effect caused by the methyl group at

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

• Peter A. Wade,
• Alma Pipic,
• Matthias Zeller and
• Panagiota Tsetsakos

Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251

• formal cycloadducts of (Z)-3-methyl-1,3-pentadiene. A Friedel–Crafts alkylation product from the reaction of the diene, β-nitrostyrene, and toluene was also obtained in 10% yield. The tin(IV)-catalyzed reaction of β-nitrostyrene with (Z)-3-methyl-1,3-pentadiene in dichloromethane afforded four nitronic

• Friedel–Crafts alkylation product of toluene and the zwitterion 11a. Zwitterion 11a would also lead to cycloadducts 4 and 7 if it cyclized. Possibly zwitterion 11a is less prone to cyclization than zwitterion 11b which leads to cycloadducts 5 and 6. The yield of cycloadduct 7 is very low in experiments