Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• . These results are summarized in Supporting Information File 1. Effect of m,m’-disubstitution The second substitution pattern investigated is the m,m’-disubstitution. By adding both substituents, the problem of the regioselectivity of addition to the arene is circumvented. The examples and results are

• radical center is not too electrophilic. Concerning the substitution pattern of the arene it was found that electron releasing substituents accelerate the addition whereas strongly electron withdrawing substituents like acyl groups retard the addition. Para-substitution has a stronger influence than meta

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• thermolysis perform intramolecular C–H insertions to produce α-halo-β-lactams. When carried out with α-bromodiazoacetamides bearing cyclic side chains, the thermolysis reaction affords bicyclic α-halo-β-lactams, in some cases in excellent yields, depending on the ring size and substitution pattern of the

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• and cyclopentane-1,3-diyls. Experimental investigation of the chemistry of singlet diradicals has become possible. The present study explores the substituents and the effect of their substitution pattern at the C(1)–C(3) positions on the lifetime of singlet octahydropentalene-1,3-diyls to understand

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

• obtained when R1 = OMe, SPh, SMe, and NMe2, at −80 °C in toluene as solvent. The influence of the substitution pattern in the aromatic ring on both the yield and the enantioselectivity is not clearly established. The introduction of electron-deficient substituents may require higher temperatures for the

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• shown in Scheme 2. We recently demonstrated [20] that variation of the aromatic substitution pattern had only a marginal influence on the HDAC inhibitory potency of psammaplin A analogues in vitro. Therefore, the native phenol was replaced by its methylated homologue for ease of synthesis, notably to

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• -dihydropyridine derivatives, which were obtained in virtually pure form in crude reaction mixtures. As evidenced with these results, 3-aryl-1,4-dihydropyridines and pyridines (5/6a–f and l–r) are readily obtained from the corresponding aryl-substituted N-allyl-ynamides regardless of the substitution pattern or

• conditions. The influence of the substitution pattern of the allyl moiety was next carefully examined and substitution at the β-, γ-positions, or both, was well tolerated, yielding the 3,5-disubstituted- (5/6l–o), 3,4-disubstituted- (5/6p–q) and 3,4,5-trisubstituted- (5/6r) 1,4-dihydropyridines and pyridines

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• consecutive carbon atoms, but the system is either lacking the desired substitution pattern or the proper degree of unsaturation (C6 + 0). A fourth possibility, the coupling of three C2 units (C2 + C2 + C2) is extremely rare and it appears that only two examples have been reported so far (see Scheme 12 and

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• by Schipper [20] and Kaneda [21], based on detailed NMR studies. According to them, the bottromycins are cyclic tetrapeptides, connected to a tripeptidic side chain through an amidine structure. The different bottromycins differ only in the substitution pattern of the proline (Figure 1). The three

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• ring fusion of C4a–N8 (1, 3 and 4) or C8a–N5 atoms (2), and differ in the arrangement of the substitution pattern of the imidazotriazine framework (Figure 1). The structural variation of imidazo[1,2,4]triazine derivatives poses a significant challenge, particularly if a broad variety of substituents is

• regioselectivity depended on the substitution pattern of 6, due to the directing effect of the methyl groups. Thus, traces of a N1-substituted regioisomer were detected by LC/ESI-MS analysis in the conversion of 5 to product 7 (N3/N1-alkylation ratio 15:1). Direct N1,N3-dialkylation of 5, however, was not observed

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• thiourea core via the sulfonimidoyl nitrogen. They differ in their aryl substitution pattern. Copper-catalyzed arylation of (S)-2 with 2-iodonitrobenzene gave rise to coupling product (S)-10 in excellent yield (98%). After subsequent reduction of the aromatic nitro group to give aniline (S)-11 in 83% yield

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• phosphanes of otherwise comparable substitution pattern. The combination of phosphanes with unusually strained cyclic substituents such as diamandoids or cyclophanes also appears to have no particularly unusual effects. Phosphanes with strongly electron-withdrawing substituents such as PF3 (303) have the

• than the one in amines. This implies that phosphanes have a more pyramidal structure than amines with a comparable substitution pattern. The least pyramidal structure is found here for triphenylamine, which is almost perfectly planar at the nitrogen atom. The degree of planarity correlates well with

• the character of the lone pair orbital. In amines the contribution of the s orbital is decreasing with increasing size of the substituents. This is different for phosphanes, where the lone pair orbital has a systematically larger s-character, which depends only marginally on the substitution pattern

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• rotation around the amide C–N moiety (partial double-bond character) in the NMR as seen by twin peaks in certain cases [25]. In carbamates 10, the substitution pattern α to the C=O group in 7–9 has shifted to the α-position next to the amino center. Therefore, in this strategy (Scheme 2) the enolate

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• between the methyl group at C-7 and the substitution pattern at C-7a and C-4a, respectively) configured iridomyrmecins. Key steps were two stereoselective hydrogenations: A transfer hydrogenation for a formal “anti” delivery of hydrogen [14][15], as represented in 5, and the use of Crabtree’s catalyst in

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

• place during and after the RCM reaction (see below). We also briefly studied the influence of the diene substitution pattern on the rate of isomerization from 4 to 3 and the corresponding product distribution (Scheme 3). Addition of in situ prepared vinyl alane to pivaloate 1 provided the diene 7 in 80

• presence of the Lewis acidic additive Ti(OiPr)4 as well as the substitution pattern of the α,ω-diene precursor. With alkene 3 and the corresponding epoxide 5 in hand, a ZnI2-mediated amine alkylation protocol could be employed, which introduced a variety of nitrogen nucleophiles 8{1–13} (Scheme 4) [38][39

• –isomerization sequence and a ZnI2-mediated epoxide aminolysis. We investigated the factors influencing the alkene isomerization during the RCM process, and identified the presence of the additive Ti(OiPr)4, the substitution pattern on the alkene, and the chemical reactivity of the benzylic allylic methine

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• most sensitive to variations in the substitution pattern (and thus, in the electronic structure) within the naphthyl systems of the binaphthyl units. The UV–vis spectra of macrocycles (R,R)-10 and (R,R)-11, recorded in solvents possessing different solvating and hydrogen-bonding abilities (CH2Cl2, EtOH

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• the lower reactivity of the diazene unit in this thioester owing to the meta-substitution pattern. The ligation reaction of 3,4'-AMPB thioester 1b with the 4,5,6-trimethoxy-2-mercaptobenzyl auxiliary peptide 5 furnished ligation peptide 12 in 38% yield (Table 1, entry 3). In this case, no hydrazine

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

• Chao Che,
• Song Li,
• Bo Yang,
• Shengchang Xin,
• Zhixiong Yu,
• Taofeng Shao,
• Chuanye Tao,
• Shuo Lin and
• Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

• smoothly in toluene with NaOt-Bu as base by using a Pd2(dba)3/rac-BINAP catalysis system [50]. Substituent-modifications on the motif D It has previously been shown that the substitution pattern on the nitrogen atom of trans-1,4-diaminocyclohexane moiety plays a critical role in the activity of the

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• quaternary carbon atoms in the 13C NMR spectrum evidenced the presence of the pyrrole structure. Finally, the HMBC experiment proved the proposed substitution pattern at the pyrrole ring. HRMS and elemental analysis allowed identification of 5 as a 2,3,4,5-tetrasubstituted pyrrole derivative. As shown in

Alkoxide-induced ring opening of bicyclic 2-vinylcyclobutanones: A convenient synthesis of 2-vinyl-substituted 3-cycloalkene-1-carboxylic acid esters

• Xiufang Ji,
• Zhiming Li,
• Quanrui Wang and
• Andreas Goeke

Beilstein J. Org. Chem. 2012, 8, 650–657, doi:10.3762/bjoc.8.72

• rings, the substitution pattern on the ring, and the properties of the reagents as well as the reaction conditions. In particular, the ring opening of certain fused-ring cyclobutanones, which are easily prepared by the well-established [2 + 2] cycloadditions of ketenes with various cycloalkenes, has

Cyanoethylation of the glucans dextran and pullulan: Substitution pattern and formation of nanostructures and entrapment of magnetic nanoparticles

• Kathrin Fiege,
• Heinrich Lünsdorf,
• Sevil Atarijabarzadeh and
• Petra Mischnick

Beilstein J. Org. Chem. 2012, 8, 551–566, doi:10.3762/bjoc.8.63

• spectroscopy (PEELS). Keywords: cyanoethyldextran; cyanoethylpullulan; ferromagnetic nanoparticles; glycan nanostructures; substitution pattern; Introduction Cyanoethylation has been widely applied to polysaccharides, e.g., to cellulose [1], inulin [2], and starch [3]. Onda reported on cyanoethylation of

• in our cyanoethylation studies. Cyanoethylglucans of different DS values were produced. Another objective of our approach was the detailed determination of the substitution pattern on the monomer level. Furthermore, nanostructuring of highly substituted cyanoethylglucans with and without

• assign and integrate all relevant resonance signals. This is obvious from the differences obtained when employing different signals for the calculation (Equation 1 and Equation 3). Only after depolymerization it was possible to determine the detailed substitution pattern by GLC analysis. In general, good

On the control of secondary carbanion structure utilising ligand effects during directed metallation

• Andrew E. H. Wheatley,
• Jonathan Clayden,
• Ian H. Hillier,
• Alison Campbell Smith,
• Mark A. Vincent,
• Laurence J. Taylor and
• Joanna Haywood

Beilstein J. Org. Chem. 2012, 8, 50–60, doi:10.3762/bjoc.8.5

• single ortho substituent [25]. At ambient temperature, amides with this substitution pattern are conformationally mobile about their aryl–CO bond [26] on a timescale of seconds or less, and hence, inseparable into atropisomers [27]. However, at the temperatures commonly used to effect lithiation

Synthesis of fluoranthenes by hydroarylation of alkynes catalyzed by gold(I) or gallium trichloride

• Sergio Pascual,
• Christophe Bour,
• Paula de Mendoza and
• Antonio M. Echavarren

Beilstein J. Org. Chem. 2011, 7, 1520–1525, doi:10.3762/bjoc.7.178

• have already been synthesized by palladium-catalyzed arylation reactions [53][54]. Strategically halogenated decacyclenes with a substitution pattern similar to that of 2 have been used for the synthesis of circumtrindene by flash vacuum pyrolysis [55]. Here we report the results on the synthesis of

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• pyrazolidinone under oxidative conditions from simple hydrazone derivatives (Scheme 1) [13]. The cascade features a [3 + 2] cycloaddition coupled with an aerobic oxidation of the resulting pyrazolidine. A further oxidative coupling may be observed according to the substitution pattern of the starting acyl

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

• product despite the isolation of 6. To establish the complete constitution of an in situ reaction mixture, it was treated with iodine, the crude 1H NMR spectrum (Figure 6) revealing that while much of the ortho- and para-substitution pattern is retained, a small portion of these zincated aryl molecules

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• should thus serve as valuable precursors in the preparation of compounds of pharmaceutical interest. Several procedures enabling the construction of the diarylmethylamide and -carbamate core have been described. However, with respect to the substitution pattern of the expected final compound, available

• strategies, mainly intended to withdraw electrons and render the carbon more electrophilic [3][4][5][6][7]. Depending on the substitution pattern of the expected final amines, the increase of the electrophilicity should be implemented through the use of activated imines (Scheme 1, pathway A) or by