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

• . Gaich et al. [38][39] used the DVCPR in a biosynthetic investigation targeting the dimethylallyltryptophan synthase. In order to test the biosynthetic hypothesis of the mode of action of the 4-prenylation of indoles by Arigoni and Wenkert (starting from L-tryptophan and dimethylallyl pyrophosphate

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• prepared in a straightforward manner. A part of the azetidine structure distinct scaffolds have been obtained from the interaction of different reactant combinations: α-aminoamides, α-aminoamidines, indoles, bis(imino)tetrahydroquinolines and tris(imino)pyrrolidines. Finally, a unified reaction mechanism

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

• . In this context, in situ made [Ph3PAuOTf] was found to be an efficient catalyst for the addition of indoles 62 to styrenes and aryldienes in toluene at 85 °C (Scheme 17a,b). Less reactive aliphatic alkenes required harsher reaction conditions, however the corresponding hydroarylation products 66 were

• by Bandini and Miscione [66][67][68] that documented on the intramolecular enantioselective allylic alkylation of indoles. Combined computational and experimental studies revealed the presence of a complex H-bond network between the indole ring, the counterion (i.e. OTf−) and the leaving OH group

• indoles to alkenes. Intermolecular [Au(III)]-catalyzed hydroarylation of alkenes with benzene derivatives and thiophene. a) Intramolecular [Au(III)]-catalyzed hydroarylation of alkenes. b) A SEAr-type mechanism was hypothesized by the authors. Intramolecular [Au(I)]-catalyzed hydroalkylation of alkenes

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• CF3-source. A single study on palladium-catalyzed trifluoromethylation of sp2-C–H bonds was reported by G. Liu and coworkers [72]. It described the introduction of a CF3 group at the 2-position of indoles using palladium acetate as a catalyst and the Ruppert–Prakash reagent TMSCF3. A screening of

• trifluoromethylation of the benzene ring as a side reaction. With these optimized reaction conditions, a series of indoles was successfully trifluoromethylated (Table 10). The nature of the substituent on nitrogen had a strong influence on yields. Alkyl or alkyl-derived groups as well as phenyl gave moderate to good

• results, but N-tosyl or N–H gave almost no desired product, if any. Indoles bearing substituents at the 2 or 3 positions were suitable substrates for respective 3- or 2-functionalization, although an ester group in position 3 led to a lower yield; a “naked” indole ring could be trifluoromethylated in a 39

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• , the copper-catalyzed N-arylation has been extensively utilized for C–N coupling, especially for the arylation of N-containing heterocycles such as indoles, imidazoles, indazoles, pyrroles, pyrazoles and triazoles [25][26][27][28] to construct more fused heterocycles. In recent years, several

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• sequence is atom economic and the application of a multicomponent reaction assures diversity. Keywords: alkynes; gold; indoles; multicomponent; spiroindolines; Ugi; Introduction The importance of nitrogen containing heterocyclic molecules in chemical biology is undisputed. The synthesis of such

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

• developed (Figure 1). Compared to the synthesis of indoles, where a number of named-reactions have been reported, only conventional methods are used for the related isoindole motif. For the construction of this rare skeleton inter- and intramolecular Diels–Alder reactions are one of the most powerful

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• ] and Rueping [83] independently reported that N-arylglycine derivatives 65 are viable substrates (Scheme 16). They are presumably converted to imines 65a that are intercepted by indoles to give the Mannich-like adducts 67. The conditions used by Li were 10 mol % Ru(bpy)3Cl2 and 1 atm O2 at 40 °C with a

• and indoles are then added to the N-acyliminium ions 68b to provide the amidoalkylation products 69. Alternatively, the use of only persulfate at 55 °C afforded the same products. However, higher yields and better selectivities were generally observed with the photocatalytic process. Intercepted by

• strategy to bypass the iminium ions and use α-amino radicals such as 112 instead to construct C–N bonds. Treatment of N,N-acetal product 111 with Grignard reagents (Scheme 26, entry 1) or indoles in the presence of TsOH (Scheme 26, entry 2) provided nucleophilic substitution products at the α carbon. This

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• knowledge, the direct alkynylation of benzofurans is still an unknown process. Since 2009, our group has developed a mild gold-catalyzed [14][15][16][17] method for the alkynylation of electron-rich aryls such as indoles and pyrroles [18], thiophenes [19], anilines [20] and furans [21]. Key for success was

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• /bjoc.9.160 Abstract This paper describes the preparation of indoles, azaindoles and benzofurans in pure water by using a new heterogeneous Pd–Cu/C catalyst through a cascade Sonogashira alkynylation–cyclization sequence. Details of the optimization studies and the substrate scope are discussed. This

• materials. Amongst the variety of heterocycles, indoles and benzofurans have emerged as privileged structures, especially in medicinal chemistry [1]. This great interest stimulated organic chemists to design efficient and diverse synthetic accesses, abundantly reviewed in the past few years [2][3][4][5][6

• ][7]. A detailed survey of the recent literature revealed that both indoles and benzofurans can be attained by a cascade Sonogashira alkynylation–cyclization sequence (Scheme 1). Many efficient catalytic systems have been reported since the pioneering studies of Yamanaka [8] and this approach is now a

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

• [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

• -linked bis(oxazoline)-Zn(II) complexes. On the other hand, indole and its derivatives are one of the most intensively investigated classical heterocycles owing to their prevalence in bioactive compounds. Indoles have been successfully utilized in asymmetric Friedel–Crafts reactions with nitroolefin and

Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

• Adam Trawczyński,
• Robert Bujok,
• Zbigniew Wróbel and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2013, 9, 934–941, doi:10.3762/bjoc.9.107

• Warszawa, Poland 10.3762/bjoc.9.107 Abstract Alkylation of 5-nitroindol-4-ylacetonitriles with ethyl chloroacetate, α-halomethyl ketones, and chloroacetonitrile followed by a treatment of the products with chlorotrimethylsilane in the presence of DBU gives 1-cyanopyrrolo[3,2-e]indoles substituted in

• -dihydropyrrolo[3,2-e]indole fragment is present in anticancer agents, such as CC-1065 [1], duocarmycin [1], and yatakemycin [2]. Some pyrrolo[3,2-e]indole derivatives show antimicrobial activity [3]. One method of synthesis of the 1,2-dihydropyrrolo[2,3-e]indoles is reduction of pyrrolo[3,2-e]indoles with sodium

• cyanoborohydride [4]. On the other hand there are many methods of synthesis of pyrrolo[3,2-e]indoles such as the copper-catalyzed transformation of tetrahydroquinoline derivatives [4], photochemical cyclization of 1,2-bis(2-pyrrolo)ethylenes [5], the Fischer indole synthesis from indol-5-ylhydrazones [3], or a

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• amines has been studied to evaluate the influence of the groups borne by the double bond on this cyclization. The results show that when this reaction takes place, it affords only the 5-exo-trig cyclization products, viz. dihydrobenzofurans or indoles. Depending on the tethered heteroatom (O or N), the

• , efficiently leading to a variety of functionalized 2-arylpyridines [17]. More recently, this nickel-catalyzed reaction provided a convenient and mild method for a one-pot synthesis of substituted benzofurans, chromans and indoles by carbonickelation of alkynes [18]. We finally decided to extend the scope of

Synthesis of 2,3-dihydronaphtho[2,3-d][1,3]thiazole-4,9-diones and 2,3-dihydroanthra[2,3-d][1,3]thiazole-4,11-diones and novel ring contraction and fusion reaction of 3H-spiro[1,3-thiazole-2,1'-cyclohexanes] into 2,3,4,5-tetrahydro-1H-carbazole-6,11-diones

• Lidia S. Konstantinova,
• Kirill A. Lysov,
• Ljudmila I. Souvorova and
• Oleg A. Rakitin

Beilstein J. Org. Chem. 2013, 9, 577–584, doi:10.3762/bjoc.9.62

• complex can convert N-substituted 2-methyl-1H-indoles to [1,2]dithiolo[4,3-b]indole-3(4H)-thiones [15]. A reaction of naphthoquinone 3a with a fivefold excess of complex 8 in chlorobenzene for 0.5 h at −20 °C with subsequent treatment with Et3N and heating at 100 °C for another 0.5 h, led to a blue solid

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• , namely isoquinolines represented by benzophenanthridines [8], oxoaporphines [9], aporphines [10] and benzylisoquinoline [11]; and quinolines represented by quinolones [12] and furoquinolines [10]. Others include carbazoles [13], pyrido-indoles [12] and quinazolines [14]. Arylethanamides and amines have

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• application in a three-component domino format are scarce [29][30]. In our laboratory, we had been employing functionalized indoles for the synthesis of annulated indole-based polyheterocycles either in a multicomponent or in a one-pot format [31][32][33][34][35]. In this continuation, we next directed our

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• closure and dehydration generates the substituted indoles 13 with high enantioselectivities (enantiomeric excess up to 86%) (Scheme 4). Different functional groups can be introduced at the C-2 position of the indoles by varying the electrophile [13][14]. The procedure has also been extended to the

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• imidazolylidene carbene ligands for the Pd-catalyzed direct arylation of pyrroles or indoles using bromobenzene and aryl iodides [42]. They observed that an important steric demand on the carbene ligand led to better results. Recently, the use of palladium(II) acetate complexes bearing both a phosphine and a

• (Scheme 1). The deviations from the accustomed structures of palladium–NHC complexes can be attributed to steric rather than to electronic factors [48]. The use of quite congested carbene ligands has been found to be required for the palladium-catalyzed direct arylation of pyrroles, indoles

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• aminoindolizines, 2-(aminomethyl)indoles, imidazopyridines, butenolides and 1,2-dihydroisoquinoline derivatives, respectively, combining these two approaches successfully. Along the same lines, we investigated a reaction between ethoxyacetylene, pyrrolidine and salicylaldehyde in the presence of a transition-metal

Palladium-catalyzed C–N and C–O bond formation of N-substituted 4-bromo-7-azaindoles with amides, amines, amino acid esters and phenols

• Rajendra Surasani,
• Dipak Kalita,
• A. V. Dhanunjaya Rao and
• K. B. Chandrasekhar

Beilstein J. Org. Chem. 2012, 8, 2004–2018, doi:10.3762/bjoc.8.227

• ][30]. Most of the literature reports are limited to aryl halides and indoles only. Clearly, each of these protocols has its own virtues; however, limitations still exist with respect to substrate scope, reagents and solvents, etc. Thus, palladium-catalyzed intra- and intermolecular cross-coupling

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• . Keywords: alkenylation; arylation; C–H functionalization; indoles; N–H functionalization; Pd catalysis; Introduction The development of mild and selective reactions for the direct conversion of carbon–hydrogen bonds into carbon–carbon and carbon–heteroatom bonds is a challenging goal in organic chemistry

• domino processes. Review Intermolecular reactions involving alkenes Alkenylation reactions of indoles run through a key C–H activation step involving an electrophilic palladation and an electron-deficient Pd(II) catalyst. The mechanism of these reactions involves the generation of a σ-alkyl complex I

• rearrangement that is operative during the alkylation of indoles [46]. In 1969, Fujiwara and Moritani reported the alkenylation of arenes catalyzed by Pd(OAc)2, using Cu(OAc)2 or AgOAc as oxidants [47]. This strategy provides a convenient method for the synthesis of olefins linked to heteroarenes, including

Arylglycine-derivative synthesis via oxidative sp³ C–H functionalization of α-amino esters

• Zhanwei Xu,
• Xiaoqiang Yu,
• Xiujuan Feng and
• Ming Bao

Beilstein J. Org. Chem. 2012, 8, 1564–1568, doi:10.3762/bjoc.8.178

• -(disubstituted amino)acetates with indoles to achieve indolylglycine derivatives (Scheme 2, reaction 1) [16]. In the course of our continuous research on the direct functionalization of sp3 C–H bonds, we found that this new strategy could also be applied to the coupling reaction of naphthols and phenols with

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

• indoles in moderate to good yields. Keywords: alkylation; C–H functionalization; cobalt; indole; vinylsilane; Introduction The indole ring ubiquitously occurs in biologically active natural and unnatural compounds [1][2][3]. Consequently, there has been a strong demand for catalytic methods allowing

• 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

• C2-lithiation with a stoichiometric lithium base or indol-2-yl radicals generated from 2-halogenated indoles [12][13][14][15][16][17]. Examples of direct C2-alkylation via transition-metal-catalyzed C–H activation are still limited [18][19][20], while Jiao and Bach recently reported an elegant

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• was the solvent of choice, and microwave irradiation was used for a shorter reaction time. The scope of the reactions was broad allowing different indoles and a variety of N,N-(dialkylamino)benzaldehydes to be employed, and the products 3 were obtained in good to excellent yields (Scheme 4) [16]. For

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

• 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

• ][19][20]. Indoles with an oxygenated stereogenic carbon at the β-position of the ring, such as indolmycin [21][22] and diolmycin [23], are known as antibiotics (Figure 1). The framework of these compounds could be constructed though the conjugate addition of an indole to α,β-unsaturated aldehydes

• FCAA reaction toward α,β-unsaturated aldehydes through iminium intermediates [32][37], and an asymmetric α-oxyamination of aldehydes via enamines [33], they are expected to be suitable for a one-pot sequential reaction to make the chiral indoles mentioned above. Herein, we report on an enantioselective