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

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• competition with a direct Friedel–Crafts-type cyclization reaction yielding 3. In previous work dealing with the cyclization of N-(3-iodoprop-2-ynyl)-N-tosylanilines to give related 1,2-dihydroquinolines (Scheme 4A, X = NTs) [43], we documented for a phosphite-based gold-catalyst, which render a more

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• ]. The synthesis commenced with the preparation of the isoindolinone building block 134. Friedel–Crafts acetylation of 132, followed by a Lieben haloform degradation gave the corresponding acid, which after methylation yielded 133. Bromination and lactam formation afforded isoindolinone 134. The

• oxalyl chloride and the Lewis acid tin(IV) chloride, a tandem cyclization (Bischler–Napieralski/Friedel–Crafts acylation reaction) was triggered to directly give 137 and 149 [122][127]. In 2006, another approach to aristoyagonine (136) was reported by the group of Couture (Scheme 20) [128]. For the

Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

• Eloi Coutant,
• Paul C. Young,
• Graeme Barker and
• Ai-Lan Lee

Beilstein J. Org. Chem. 2013, 9, 1797–1806, doi:10.3762/bjoc.9.209

• Eloi Coutant Paul C. Young Graeme Barker Ai-Lan Lee Institute of Chemical Sciences, Heriot-Watt University, Edinburgh, EH14 1LP, United Kingdom 10.3762/bjoc.9.209 Abstract A gold(I)-catalysed reaction of allylic alcohols and phenols produces chromans regioselectively via a one-pot Friedel–Crafts

• allylation/intramolecular hydroalkoxylation sequence. The reaction is mild, practical and tolerant of a wide variety of substituents on the phenol. Keywords: allylic alcohols; chromans; Friedel–Crafts; gold catalysis; heterocycles; Introduction Chromans (dihydrobenzopyrans) are important and ubiquitous

• structural motifs found in a variety of important biologically active natural products such as vitamin E and flavanoids [1][2][3][4][5]. One approach towards chromans [6][7][8][9][10][11][12], which is biosynthetically inspired, is the Friedel–Crafts allylation [13] of phenols followed by cyclisation of the

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• Jiahuan Peng Da-Ming Du School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, China 10.3762/bjoc.9.137 Abstract The enantioselective tandem Friedel–Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by a

• diphenylamine-linked bis(oxazoline)-Zn(OTf)2 complex was investigated. This tandem reaction afforded functionalized chiral chromans in good yields with moderate to high stereoselectivities (up to 95:5 dr, up to 99% ee). Keywords: asymmetric catalysis; bis(oxazoline); chroman; Friedel–Crafts alkylation; tandem

• [21][22][23][24][25][26][27][28][29][30][31][32]. Chiral indolyl(nitro)chromans have been successfully synthesized in our previous study [33]. Good results were obtained in the diastereo- and enantioselective Friedel–Crafts alkylation of indoles with 3-nitro-2H-chromenes catalyzed by diphenylamine

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• product within the microdroplets to be visualised accurately (Figure 6). Another beneficial way to use a camera to assist in a reaction optimisation is simply to see what is happening in an otherwise inaccessible reaction vessel or closed cavity. During studies on the Friedel–Crafts alkylation of anisole

• setup that might not otherwise be available. Suzuki–Miyaura reaction performed within a microfluidic system. The product is observed by high-speed microscope photography, which shows a precipitate forming within the microdroplets. Friedel–Crafts reactions performed by using solid-acid catalysis at high

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• nucleophiles [5][6][7][8][9][10], in Friedel–Crafts alkylations [11][12][13][14], and Baylis–Hillman reactions [15][16][17][18]. Furthermore, nitroalkenes can react as dipolarophiles in [3 + 2] cycloadditions [19][20][21][22], as dienophiles in [4 + 2] cycloadditions [23][24][25][26], and as heterodienes in

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• –cyclisation leading to indoline 97 with an intramolecular Friedel–Crafts reaction to afford a tricyclic derivative 98 substituted by a trifluoromethyl group [44]. The second exploits the presence of both a protected primary amine and an easily substitutable chlorine on the pyrimidine ring in 99a,b to afford

• , which smoothly undergoes an intramolecular Friedel–Crafts reaction to generate the last ring in intermediate 169. Finally, reduction of the lactam and unmasking of the ketone causes the migration of the olefin to complete the synthesis of the target structure 170. The generation of radicals using nickel

Polymerization of novel methacrylated anthraquinone dyes

• Christian Dollendorf,
• Susanne Katharina Kreth,
• Soo Whan Choi and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 453–459, doi:10.3762/bjoc.9.48

• absorption in two different areas of the visible spectrum. Polymerizable blue dye 6 based on anthraquinone For the synthesis of the blue anthraquinone based monomeric dye 6, the precursor 1,4-dichloroanthraquinone (3) was prepared by the reaction of 1,4-dichlorobenzene with phthalic dichloride by Friedel

• –Crafts acylation followed by an acidic ring closure (Scheme 1, step b). In further reaction steps, 1,4-dichloroanthraquinone (3) and hydroxyaniline were reacted to obtain 1,4-bis(4-hydroxyphenylamino)anthraquinone (4). Subsequent reaction with 2-bromoethanol gave 1,4-bis(4-((2-hydroxyethyl)oxy

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• reagents to afford 1,1-disubstituted olefins [27]. Alternatively, Friedel–Crafts-type alkenylation could be a better choice to prepare such regiospecific vinyl aromatic compounds. Yamaguchi et al. reported a direct ortho alkenylation of phenols with 1-alkynes using SnCl4 and Bu3N in acetonitrile under

• reflux [28]. Further developments include the metal trifluoromethanesulfonate-catalyzed Friedel–Crafts alkenylation of arenes using alkynes by Tsuchimoto et al. [29] and the addition of simple arenes to arylacetylenes to afford exclusive 1,1-diarylethylenes through a C–C coupling reaction catalyzed by a

• (III) chloride [32]. Nevertheless, all of these Lewis acid catalyzed Friedel–Crafts-type reactions have their own limitations. Being homogeneous catalytic systems, these methods suffer from drawbacks, such as difficulty in recovery and reusability of the catalysts and tedious work-up procedures. In

An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H)-one derivatives

• Wentao Gao,
• Guihai Lin,
• Yang Li,
• Xiyue Tao,
• Rui Liu and
• Lianjie Sun

Beilstein J. Org. Chem. 2012, 8, 1849–1857, doi:10.3762/bjoc.8.213

• , is described, involving the intramolecular Friedel–Crafts acylation reaction of 2-(phenoxymethyl)-4-phenylquinoline-3-carboxylic acid derivatives 3a–l aided by the treatment with PPA (polyphosphoric acid) or Eaton’s reagent. The required starting compound (2) was obtained by Friedländer reaction of 2

• three-step route, offers easy access to tetracyclic-fused quinoline systems in short reaction times, and the products are obtained in moderate to good yields. Keywords: Eaton’s reagent; Friedel–Crafts acylation; Friedländer reaction; one-pot; PPA; quinoline; tetracyclic-fused; Introduction Polycyclic

• nature of the bulky tert-butyl group at the o-position of aryl. Thus, the resulting substrates, quinoline-3-carboxylic acids 3a–l, further served as active synthons for the intramolecular Friedel–Crafts acylation reaction to construct the desired tetracyclic benzoxepino-fused quinoline systems. Of the

C2-Alkylation of N-pyrimidylindole with vinylsilane via cobalt-catalyzed C–H bond activation

• Zhenhua Ding and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2012, 8, 1536–1542, doi:10.3762/bjoc.8.174

• different when it comes to direct C–H alkylation [10][11]. The intrinsically nucleophilic C3 position of indole is amenable to a variety of catalytic alkylation reactions such as Friedel–Crafts reaction [5]. On the other hand, C2-alkylation of indoles has traditionally required 2-lithioindoles generated by

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• -functionalized indole or pyrrole derivatives in a highly enantioselective manner. Keywords: Friedel–Crafts-type alkylation; laccase; one-pot reaction; organocatalysis; α-oxyamination; resin-supported peptide catalyst; Findings Indole derivatives represent a class of biologically active compounds [1][2][3], and

• they often have chiral carbon chains attached to indole rings. A Friedel–Crafts-type asymmetric alkylation (FCAA) to indoles is a versatile method for synthesizing such chiral indole derivatives. To date, a number of FCAA reactions by either metal catalysts or organocatalysts have been reported [4][5

• -pot sequential Friedel–Crafts-type alkylation/α-oxyamination. Examples of the one-pot synthesis of oxygenated heteroaromatic compounds. Supporting Information Supporting Information File 340: Typical experimental procedure, spectroscopic data for products, determination of stereochemistry, 1H and 13C