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

• amine counterpart under high reaction temperatures, preferably under heating to more than 180 °C or through the use of microwave irradiation, results in the amino-7-azaindole in moderate to low yield [5][7]. Primary alkylamines or anilines under similar reaction conditions provided the displacement

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

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

• ]. One well-known example of the “tert-amino effect” is the cyclization of N,N-dialkyl-substituted anilines with imines to generate cyclic aminals. The groups of Seidel and Akiyama independently reported mild organocatalytic approaches to cyclic aminals involving aminobenzaldehydes and primary amines [10

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• } (Figure 4). Interestingly, even with substoichiometric amounts considerable formation of indoles was observed. Very common byproducts are anilines [45][46][47]. It should be noted at this point that the anilines are more prone to cleavage during the Bartoli reaction, and this led to a high purity (albeit

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• good yields and high stereoselectivities. Follow-up transformations of the primary products provided (E)-1-alkenyl-(pentafluorosulfanyl)benzenes and 2-(2-arylethyl)-(pentafluorosulfanyl)anilines. Keywords: Horner–Wadsworth–Emmons reaction; pentafluorosulfanyl group; phosphonates; sulfurpentafluoride

• nitrogen [18] nucleophiles, and the oxidative nucleophilic substitution with Grignard and alkyllithium reagents [19]. Reduction of the nitro group in 1 or 2 to (pentafluorosulfanyl)anilines followed by acylation, SEAr halogenation or diazotization (with follow-up reactions) has also been described [11][20

• Raney nickel did not provide full conversion to the respective anilines. Furthermore, the reaction mixtures contained products 7 and 8. At higher pressure (20 atm), complete nitro group and C=C reduction of stilbenes 5 and 6 to compounds 7 and 8, respectively, took place (Table 4). Several other

Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• ]. Co(ClO4)2 hexahydrate could also be used in place of ZnI2, but was generally less efficient (Table 1). Anilines with electron-withdrawing (CF3, CN, CO2Et), electron-donating (OCH3), and halogen substituents (F, Cl, Br) in ortho-, meta- and para-positions were used (Figure 5). Furthermore

Regioselective chlorination and bromination of unprotected anilines under mild conditions using copper halides in ionic liquids

• Han Wang,
• Kun Wen,
• Nurbiya Nurahmat,
• Yan Shao,
• He Zhang,
• Chao Wei,
• Ya Li,
• Yongjia Shen and
• Zhihua Sun

Beilstein J. Org. Chem. 2012, 8, 744–748, doi:10.3762/bjoc.8.84

• Science, Shanghai, 201620, China 10.3762/bjoc.8.84 Abstract By using ionic liquids as solvents, the chlorination or bromination of unprotected anilines at the para-position can be achieved in high yields with copper halides under mild conditions, without the need for potentially hazardous operations such

• procedures. Regioselectivity with electron-rich substrates such as aniline will predominantly produce para- and ortho-substitutions. However, chlorination or bromination of aniline derivatives is often performed with protected anilines. This increases both the cost of synthesis and the environmental impact

• -substituted anilines excellent results were obtained in terms of isolated yields of the desired 4-Cl products, which ranged from 85–96% (Table 2, entries 1–9, see Supporting Information File 1). The substitutions ranged from electron-donating substituents, such as the methoxy group, to electron-withdrawing

Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

• Mohamed Abboud,
• Emmanuel Aubert and
• Victor Mamane

Beilstein J. Org. Chem. 2012, 8, 253–258, doi:10.3762/bjoc.8.26

• obtained in this reaction (Table 1, entries 1–6). Aniline 6g bearing an electron withdrawing trifluoromethyl group led to a low yield of 3g (Table 1, entry 7) whereas no cyclized product was observed with other electron-deficient anilines 6h–j and carbamate 7 (Figure 1). Other methods to react 7 with

• use of the palladium-catalyzed double N-arylation of electron-rich anilines as the key reaction, the diazacarbazoles were regioselectively generated. Crystal structure determination shows that these molecules interact mainly through π–π stacking. The reported synthesis should widen the use of

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

• Nan Sun,
• Bin Li,
• Jianping Shao,
• Weimin Mo,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2012, 8, 61–70, doi:10.3762/bjoc.8.6

• – were employed, a significant amount of 1,3-diphenylthiourea (2-2) was formed; this resulted in the low selectivity for N-phenyl dithiocarbamate (2-1) (Table 1, entry 1 and 2) despite a high conversion observed for the anilines. When weaker bases – such as NH4OH, Na2CO3 and NaHCO3 – were used, the

Imidazole as a parent π-conjugated backbone in charge-transfer chromophores

• Jiří Kulhánek and
• Filip Bureš

Beilstein J. Org. Chem. 2012, 8, 25–49, doi:10.3762/bjoc.8.4

• inexpensive and readily available compounds (Scheme 1). Typical representatives of benzimidazole-derived D-π-A systems are shown in Figure 11. In 2004, Carella, Centore, and co-workers [25] reported the synthesis and further application of nitrobenzimidazole-derived anilines 35 and 36. These two compounds

PEG-embedded KBr₃: A recyclable catalyst for multicomponent coupling reaction for the efficient synthesis of functionalized piperidines

• Sanny Verma,
• Suman L. Jain and
• Bir Sain

Beilstein J. Org. Chem. 2011, 7, 1334–1341, doi:10.3762/bjoc.7.157

• conditions (see Experimental). The reaction proceeded efficiently and afforded a high product yield under mild reaction conditions. These successful results prompted us to extend the scope of the reaction with a variety of aldehydes, substituted anilines and β-keto esters under identical reaction conditions

• . The results of these experiments are summarized in Table 1. In all cases we achieved moderate to high yields of the products, which were identified by comparing their physical and spectral properties with those of authentic samples. Among the various anilines, the reaction was found to be faster with

• anilines having electron donating groups, whereas the reaction was found to be slow with aniline, which contains an electron-withdrawing group (Table 1, entry 12). Similarly the reaction was found to be very slow in the case when both aniline and aldehyde were substituted with electron-withdrawing groups

Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

• Stephen P. Fletcher,
• Jordi Solà,
• Dean Holt,
• Robert A. Brown and
• Jonathan Clayden

Beilstein J. Org. Chem. 2011, 7, 1304–1309, doi:10.3762/bjoc.7.152

• to make mixtures containing detectable quantities of unequal pairs of diastereoisomeric derivatives. We have previously made isotopically labelled anilines [6] for related studies on oligo-urea foldamers [7][8][9]. Achiral quaternary amino acids such as Aib and its substituted congeners are powerful

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

• Paul Knochel,
• Matthias A. Schade,
• Sebastian Bernhardt,
• Georg Manolikakes,
• Albrecht Metzger,
• Fabian M. Piller,
• Christoph J. Rohbogner and
• Marc Mosrin

Beilstein J. Org. Chem. 2011, 7, 1261–1277, doi:10.3762/bjoc.7.147

• followed by an iodination with iodine and Ag2SO4 furnishes the tetrasubstituted aniline 125. Protection of the free amino-group followed by a Negishi-reaction provides the scaffold 126 in 80% yield (Scheme 20). Successive magnesiations at the positions 5 and 3 of the tetrasubstituted anilines 126 with

Meta-metallation of N,N-dimethylaniline: Contrasting direct sodium-mediated zincation with indirect sodiation-dialkylzinc co-complexation

• David R. Armstrong,
• Liam Balloch,
• Eva Hevia,
• Alan R. Kennedy,
• Robert E. Mulvey,
• Charles T. O'Hara and
• Stuart D. Robertson

Beilstein J. Org. Chem. 2011, 7, 1234–1248, doi:10.3762/bjoc.7.144

• and Discussion The original direct meta-zincation reaction. In comparison to tertiary amides and O-carbamates, anilines are relatively modest metallation directing groups [19][29]. Activation of N,N-dimethylaniline transpires primarily from the acidifying effect of the N atom; the coordination effect

• keeping with conventional metallation chemistry exhibits ortho-deprotonated anilines. The instability of 3 at ambient temperatures is reflected in its deprotonation of toluene under mild conditions and following co-complexation with the dialkyl zinc, a mixture of two products were isolated from the

Reductive amination with zinc powder in aqueous media

• Giovanni B. Giovenzana,
• Daniela Imperio,
• Andrea Penoni and
• Giovanni Palmisano

Beilstein J. Org. Chem. 2011, 7, 1095–1099, doi:10.3762/bjoc.7.125

• detected, probably due to minor stabilization of aminoalkyl–radical intermediates involved in the reduction step. Additional examples (entries i to l) were explored with different combinations of isomeric hydroxybenzaldehydes and amines showing the successful reactivity of anilines and the compatibility of

Novel synthesis of pseudopeptides bearing a difluoromethyl group by Ugi reaction and desulfanylation

• Jingjing Wu,
• Hui Li and
• Song Cao

Beilstein J. Org. Chem. 2011, 7, 1070–1074, doi:10.3762/bjoc.7.123

• group (PhS) with Bu3SnH/AIBN according to our previous research, and the desired difluoromethyl-containing pseudopeptide was successfully obtained [27]. To demonstrate the scope of the method, several different substituted anilines, substituted benzaldehydes, isocyanides and this novel difluorinated

• difluoromethyl-containing pseudopeptides (3a–m and 4a–m) in good yields (Table 1). Conclusion In summary, we have developed a novel and efficient protocol for the synthesis of CF2H-containing pseudopeptides by Ugi reaction of substituted anilines, benzaldehyde, isocyanides and the novel building block 2,2

Multicomponent reaction access to complex quinolines via oxidation of the Povarov adducts

• Esther Vicente-García,
• Rosario Ramón,
• Sara Preciado and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2011, 7, 980–987, doi:10.3762/bjoc.7.110

• through the Povarov MCR (the interaction of anilines, aldehydes and activated olefin inputs under acid catalysis) [4][5][6][7][8]. Interestingly, this process allows cyclic enol ethers and enamines to be used as electron-rich alkenes, leading to heterocycle-fused tetrahydroquinolines, usually as a mixture

• , anilines and activated alkenes in a short sequence, involving Povarov MCR and oxidation steps. Experimental General 1H and 13C NMR spectra were recorded on a Varian Mercury 400 spectrometer. Unless otherwise stated, NMR spectra were recorded in CDCl3 solution with TMS as an internal reference. Data for 1H

Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates

• Wang-Yong Yang,
• Samantha A. Marrone,
• Nalisha Minors,
• Diego A. R. Zorio and
• Igor V. Alabugin

Beilstein J. Org. Chem. 2011, 7, 813–823, doi:10.3762/bjoc.7.93

• produced acetylenes 8a–c. The TMS group of acetylene 8 was directly substituted with a tetrafluoropyridyl (TFP) group by a CsF-promoted reaction with pentafluoropyridine in DMF. Reduction of the nitrobenzenes 9a–c with SnCl2 produced anilines 10a–c, which were reacted with acetyl chloride to form amides 3

• , 4, and 5 (Scheme 2). Conjugates 1, 6, and 7 were prepared via coupling of the corresponding anilines 10a–c with Boc-protected lysine in the presence of POCl3 in pyridine. The Boc groups were removed by treatment with gaseous HCl in MeOH. Photochemical reactions of TFP-alkynes with 1,4-cyclohexadiene

One-pot gold-catalyzed synthesis of 3-silylethynyl indoles from unprotected o-alkynylanilines

• Jonathan P. Brand,
• Clara Chevalley and
• Jérôme Waser

Beilstein J. Org. Chem. 2011, 7, 565–569, doi:10.3762/bjoc.7.65

• -pot procedure with the Au(I)-catalyzed C3-selective direct alkynylation of indoles using the benziodoxolone reagent TIPS-EBX to give a mild, easy and straightforward entry to 2-substituted-3-alkynylindoles. The reaction can be applied to unprotected anilines, was tolerant to functional groups and easy

• alkynylation with bromoacetylenes [29]. New methods are needed to expand the scope of this transformation and Au catalysis appears especially promising, due to its broad functional groups tolerance, which could allow the direct use of unprotected anilines. Recently, the direct alkynylation of preformed

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• some cases, the up to stoichiometric amount of ligand made work-up procedures difficult. In general, CuI is the most efficient catalyst. The reaction conditions are applicable to primary, cyclic secondary aliphatic amines, electron-rich and electron-poor anilines, and heteroarylamines. Macrocyclization

Aromatic and heterocyclic perfluoroalkyl sulfides. Methods of preparation

• Vladimir N. Boiko

Beilstein J. Org. Chem. 2010, 6, 880–921, doi:10.3762/bjoc.6.88

• NO2, CF3 or COCl in the aromatic ring of trichlorothioanisole does not influence the fluorination and the reaction is not hindered by bulky ortho-substituents e.g., phthalic acid imide [53] or N-substituted anilines [54]. Other reactive substituents, for example 3-SCCl3 or 4-COCl are also fluorinated

• anilines but also for N-monosubstituted substrates and even those with a free NH2 group (Scheme 11). In naphthalene and benzophenone derivatives only those rings containing hydroxy or amino groups undergo perfluoroalkylsulfanylation [74][75]. Other electron-donating substituents on the aromatic ring are

EPR and pulsed ENDOR study of intermediates from reactions of aromatic azides with group 13 metal trichlorides

• Giorgio Bencivenni,
• Riccardo Cesari,
• Daniele Nanni,
• Hassane El Mkami and
• John C. Walton

Beilstein J. Org. Chem. 2010, 6, 713–725, doi:10.3762/bjoc.6.84

• suggested that the unpaired electrons were accommodated in extensive π-delocalised orbitals. A mechanism to account for the reductive conversion of aromatic azides to the corresponding anilines and thence to the dimers and trimers is proposed. Keywords: aluminium; aromatic azides; ENDOR; EPR; gallium

• reports show that anilines can easily be oxidised to the corresponding resonance-stabilised radical cations, which can couple with more aniline to afford very persistent radical cation dimers [37][38]. The generation of these radical cations depends critically on the reaction conditions, in particular on

• the degree of protonation, which can facilitate electron transfer (ET) [39][40]. It has also been reported that electrochemical oxidation of aromatic amines can generate the same radical cations which can polymerise giving oligo- and poly-anilines [41]. In view of the fact that product analyses [31

Synthesis, electronic properties and self-assembly on Au{111} of thiolated (oligo)phenothiazines

• Adam W. Franz,
• Svetlana Stoycheva,
• Michael Himmelhaus and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2010, 6, No. 72, doi:10.3762/bjoc.6.72

• ] qualifies them as excellent models for switchable conductive or semiconductive molecular wires. Encouraged by successful electrode modifications with conjugated thiolated anilines [38] and SAM formation of thiolated phenylethynyl phenothiazines [39], and in continuation of our investigations directed

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• which provided the products with high enantioselectivities. Beside indoles, anilines have gained much attention as target for hydroarylation reactions. However, the main issues for FC alkylations of anilines are the deactivation of the catalyst due to coordination of the primary amine and/or concurrent

• hydroamination reactions [66]. Nevertheless, Beller et al. developed a valuable method to overcome these limitations. In 1999 they described the transition metal catalyzed hydroarylation of anilines 46 with styrenes using a cationic Rh-complex [67]. Depending on the aniline derivative, a combination of 2.5 mol

• % [Rh(cod)2]BF4, 4 mol% PPh3 and HBF4•OEt2 was necessary for sufficient reactivity; yet electron-rich and N-alkylated anilines react without a metal catalysis in the presence of catalytic amounts of HBF4 (Scheme 20). About the same time a Ru3(CO)12-catalyzed hydroarylation of anilines was reported as

Iridium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with secondary amine nucleophiles

• Dingqiao Yang,
• Ping Hu,
• Yuhua Long,
• Yujuan Wu,
• Heping Zeng,
• Hui Wang and
• Xiongjun Zuo

Beilstein J. Org. Chem. 2009, 5, No. 53, doi:10.3762/bjoc.5.53

• catalyst. The trans-1,2-dihydronaphthalenol product 2 is subsequently released and the iridium monomer B is regenerated. Conclusion In summary, we have explored the iridium-catalyzed ARO reaction of oxabicyclic alkenes with N-alkylated anilines or N-substituted piperazine nucleophiles; the reactions gave

Synthesis of rigidified flavin–guanidinium ion conjugates and investigation of their photocatalytic properties

• Harald Schmaderer,
• Mouchumi Bhuyan and
• Burkhard König

Beilstein J. Org. Chem. 2009, 5, No. 26, doi:10.3762/bjoc.5.26

• the presence of sacrificial electron donor substrates, such as aliphatic amines, flavins can photoreduce nitro arenes to anilines under blue light irradiation (Scheme 4). 4-Nitrophenyl phosphate was used as a substrate for photoreduction in water and in acetonitrile. The results summarized in Table 2