Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• demonstrate the regiochemistry of the reaction. These cascade reactions proceed first through a Michael addition of the primary amine on the enone, followed by an intramolecular cyclization by the pyridine/pyrimidine nucleus. Unfortunately, no crystal structure could be obtained for the imidazopyrimidines and

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• intermediates, and from these data it was possible to explain the regiochemistry of the products obtained. Additionally, the data were a useful tool for elucidating the reaction mechanisms. Keywords: DFT-B3LYP; polyazaheterocycles; pyrazinone; pyrido[1,2-a]pyrimidinone; pyrimido[1,2-a]benzimidazole

• regiochemistry of the products [11]. Saiz et al. [14] synthesized 2-hydrazolyl-4-thiazolidinones with the aid of semi-empirical calculations (PM3 method). Through HOMO/LUMO energies, orbital coefficients, and charge distribution, a mechanism was proposed explaining the products observed. The authors claimed that

• the HOMO/LUMO energy gap is small and that the reaction between thiosemicarbazone and benzyl is kinetically favored, probably controlled by the frontier orbital component. Furthermore, calculations of HOMO and LUMO frontier orbital coefficients were used to prove the regiochemistry in cycloaddition

Effects of solvent additive on “s-shaped” curves in solution-processed small molecule solar cells

• John A. Love,
• Shu-Hua Chou,
• Ye Huang,
• Guilllermo C. Bazan and
• Thuc-Quyen Nguyen

Beilstein J. Org. Chem. 2016, 12, 2543–2555, doi:10.3762/bjoc.12.249

• regioselective Stille conditions [37] in an oil bath (90 °C) to generate 2. (Complete synthetic details and characterization of all compounds are provided in Supporting Information File 1). Its fluorine regiochemistry was confirmed by 1H-1H NOESY spectroscopy (Supporting Information File 1, Figure S1). Compound

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• signals for pyrrolidine ring protons: a singlet at 2.05–2.18 ppm for N(1’)Me group protons, two triplets at 3.49–3.66 and 3.93–4.05 ppm assignable to the protons of methylene C(5’)H2 group, and one triplet at 4.45–4.70 ppm corresponding to the proton of C(4’)H. This clearly demonstrates the regiochemistry

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• Information File 1). NMR studies To establish the stereochemistry and/or regiochemistry of the azidation and CuAAC steps, homo- or heteronuclear 2D NMR experiments (see Supporting Information File 2) were performed on compounds 2 and 3a (Figure 2). In addition, we synthesized compound 5 (resulting from an 1,5

• and two signals for the olefin carbon atoms at δ = 148.4 ppm and δ = 119.3 ppm for the C4 and the C5, respectively. The regiochemistry of the cycloaddition was unambiguously established using heteronuclear multiple bond correlation (HMBC) experiments to identify long-range (generally 2- or 3-bonds

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• yields. The CuAAC reaction of 1 with aryl azides such as 4-methylphenyl and 4-cyanophenyl azide gave a complex mixture, presumably due to the steric hindrance introduced by the aryl groups. The regiochemistry of 5-stibanotriazole 3a was elucidated by 1H NMR and confirmed by single-crystal X-ray analysis

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• regarding the regiochemistry of carbenoid insertion into C(sp3)–H bonds, and also the steric and electronic factors related to this insertion. The first example of an enantioselective carbenoid insertion reaction in chemical bonds catalyzed by chiral metal complexes was introduced in 1966 by Noyori and

• cyclopropylcarboxylate ligand (Scheme 17) [60]. This new ligand favors the regiochemistry of rhodium carbenoid insertion into primary C(sp3)–H activated bonds even in the presence of activated secondary C(sp3)–H bonds. This preference stems from the greater volume of the ligand and the consequent greater steric strain

• 2,2,2-trichloroethyl (TCE) aryldiazoacetates (Scheme 19) [61]. When compared with the use of traditional methylaryldiazoacetates (Scheme 17), an improved enantioselectivity of the insertion product 85 was observed combined with superior regiochemistry, favoring the rhodium carbenoid insertion into

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• of predominantly 3´,5´-regiochemistry were formed by this method. Elemental sulfur may have been abundant on primitive Earth but its availability is limited by its poor solubility. In the present study this problem was addressed by carrying out the model reaction in toluene. On primitive Earth

• had H-phosphonothioate, rather than phosphate termini. Evidently sulfurization and esterification of H-phosphonate monoesters compete under the experimental conditions. Determination of the regiochemistry of the phosphorothioate linkages To establish the regiochemistry of the phosphorothioate linkages

• experiment indicate that nearly 80% of the internucleosidic linkages formed upon condensation of thymidine and triethylammonium phosphite in the presence of sulfur had the natural 3´,5´-regiochemistry. The most likely explanation for this regioselectivity is the faster phosphitylation of the primary 5

Synthesis and reactivity of aliphatic sulfur pentafluorides from substituted (pentafluorosulfanyl)benzenes

• Norbert Vida,
• Jiří Václavík and
• Petr Beier

Beilstein J. Org. Chem. 2016, 12, 110–116, doi:10.3762/bjoc.12.12

• temperature with exclusive regiochemistry on the less substituted double bond of 12 and complete endo stereochemistry (Scheme 5). Employing density functional theory (DFT) with the B3LYP functional [23] and the aug-cc-pVDZ basis set [24][25], we calculated the reaction coordinates leading to four possible

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• , performed at 300 MHz, using C6D6 or CDCl3 as solvents. In particular, the regiochemistry and stereochemistry around the C1/C4 moiety were assigned on the basis of spatial coupling interactions detected by 2D-NOESY experiments. As an example, the regiochemistry of the Diels–Alder adducts 3a and 3'a was

Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• catalysis and amidyl radicals, a concerted mechanism has been ruled out and a polar mechanism via chloronium ions would lead to the opposite regiochemistry. Keywords: addition reactions; catalysis; N-chlorosulfonamides; haloamination; radical reaction; Introduction In earlier publications we described the

• addition of 2b (Scheme 4). This result surprised us, as we did not regard the chloroamide as a chloronium ion source. For the addition reactions to styrenes a polar mechanism can be ruled out due to the observed regiochemistry, however, in all other cases a polar mechanism is possible too and we therefore

• [39], producing an acyclic product. Upon copper(I) catalyzed addition of 2a to vinylcyclopropane only the ring-opend product 15 was obtained, which rules out a concerted mechanism and is, due to the observed regiochemistry, a strong indication for a radical pathway of the addition reaction (Scheme 5

Regio- and stereoselective synthesis of new diaminocyclopentanols

• Evgeni A. Larin,
• Valeri S. Kochubei and
• Yuri M. Atroshchenko

Beilstein J. Org. Chem. 2014, 10, 2513–2520, doi:10.3762/bjoc.10.262

• aminocyclopentanols 8c and 8d (Supporting Information File 1). In every experiment, 1,2-trans-2,3-cis-aminocyclopentanols, arising from opening of epoxide 3a at C1, were the only regioisomers isolated. The stereo- and regiochemistry of 8a and 8d were assigned by 2D NMR (HSQC-DEPT, 1H,1H COSY and NOESY experiments

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• caused an unusual activation of the alcohol moiety, leading to N-alkylation. In the presence of iPr2NEt, reaction of HATU with benzyl-, n-butyl-, and p-nitrobenzyl alcohol led to the formation of the corresponding 1-alkoxy-1H-7-azabenzotriazoles [39]. The regiochemistry in these reactions was identical

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• strong hydrogen bond between the amino hydrogen and the nitro group. In contrast, lacking the opportunity to build such a hydrogen bridge, the regiochemistry of compound 20 (also formed as one single isomer) remained unclear. With the thiazolidinones in hand, in the case of 7, 8, 10, and 12 we carried

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• -box for allylic hydroxylation in synthetic chemistry. Keywords: allylic hydroxylation; cytochrome P450; natural products; protein engineering; regiochemistry; terpenoids; Introduction Direct allylic hydroxylation yielding highly valuable allylic alcohols has been recognised for a while as one of the

• enzymes produce different ratios of epoxidised and hydroxylated products [17][18][19]. The exact factors that govern the regiochemistry of P450 enzymes remain not completely understood [16]. In our previous studies we demonstrated the effects of the substrate stereochemistry on enzyme regio- and

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• radical cation 29. Finally, Ru(bpz)31+ reduces amine radical cation 29 to the annulation product 30 while regenerating Ru(bpz)32+. The proposed mechanism accounts for lower reactivity of alkynes towards intermolecular addition of nucleophilic carbon-centered radicals as well as their regiochemistry in the

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• ether, yielding the desired monobenzoate in moderate yield (60%) after purification. The regiochemistry of the ring opening was revealed in the HMBC spectrum of monobenzoate 33b. The 1H NMR signal corresponding to the C-2 methine proton couples (3JC-H) to both carbonyl signals in the 13C spectrum. This

• indicates that both carbonyl groups are within 3 bonds of the hydrogen on C-2. However, the signal from the hydrogen on C-3 couples to the carbonyl carbon of the n-propyl ester only, confirming the expected regiochemistry for structure 33b. Dibenzoate 34b was synthesised (32% overall from 28b) directly from

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• )-Binap·AuTFA]2. The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert

• as well as possible regiochemistry of the selected 1,3-DC, were considered. The main geometrical features of the less energetic transition structures are depicted in Figure 7. Our calculations show that the less energetic transition structure associated with the 1,3-DC of 10 and tert-butyl acrylate

• kcal mol−1 lower in energy than the endo analogue (TS11exo vs TS11endo in Figure 7). Moreover, the a priori expected regiochemistry of the cycloaduct, in which C2–Cβ and C5–Cα are new bonds (12), was considered. In this case, TS12 is 12.1 kcal mol−1 higher in energy than TS11exo. It is noticeable that

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

• Ashley N. Jarvis,
• Andrew B. McLaren,
• Helen M. I. Osborn and
• Joseph Sweeney

Beilstein J. Org. Chem. 2013, 9, 852–859, doi:10.3762/bjoc.9.98

• mixture of all three possible ring-opened products being isolated. Two of these compounds arose from SN2-like reaction at C-1 and C-2 while the other is produced via an SN2′-like reaction at C-4. Clearly, the "softness" of the nucleophile does have an effect on the regiochemistry of the ring-opening

Titanium-mediated reductive cross-coupling reactions of imines with terminal alkynes: An efficient route for the synthesis of stereodefined allylic amines

• Kebin Mao,
• Guoqin Fan,
• Yuanhong Liu,
• Shi Li,
• Xu You and
• Dan Liu

Beilstein J. Org. Chem. 2013, 9, 621–627, doi:10.3762/bjoc.9.69

• -ray crystal structure of compound 5c. X-ray crystal structure of compound 8. Titanium-mediated cross-coupling of imines with terminal alkynes. Synthesis of allylic amine 5a by titanium-mediated coupling reaction of imine 2a with 1-heptyne. The regiochemistry of titanium-mediated cross-coupling of

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• : carbometallation; enamides; organocopper; regiochemistry; ynamides; Introduction Due to a strong differentiation of electron density on the two sp-hybridized carbon atoms, N-alkynylamides (ynamides) have become attractive substrates involved in many synthetically useful transformations [1][2][3][4]. The

• -alkynylsulfonamide 2 as yields could reach 68 and 84%, respectively (Table 2, entries 8 and 9). Yield could be further improved when CuBr·Me2S was used as the copper source (Table 2, compare entries 1 and 6) [25]. In all cases, the expected α-isomer of 6 was exclusively formed and the regiochemistry was determined

Design and synthesis of a photoswitchable guanidine catalyst

• Philipp Viehmann and
• Stefan Hecht

Beilstein J. Org. Chem. 2012, 8, 1825–1830, doi:10.3762/bjoc.8.209

• strength, are strongly dependent on its microscopic structure. It is well known that this structure, which is characterized by parameters such as molecular weight and distribution, composition, regiochemistry and stereochemistry (tacticity), critically depends on the interaction between catalyst and

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• considerably cleaner reaction. Separation of a major and minor product was achieved, with the major product identified as the tryptophan derivative 2a, isolated in 63% yield. The regiochemistry of 2a was established through correlation spectroscopy. A 2J correlation between the ipso-carbons of both aromatic

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

• -octene (2e) was even more sluggish, affording the alkylation product 3ae in only 9% yield (Scheme 3b). Styrene also reacted rather sluggishly to afford only a small amount of the alkylation product (3% as estimated by GC and GCMS), the regiochemistry (branched versus linear) of which has yet to be

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

• Sarah L. Harding,
• Sebastian M. Marcuccio and
• G. Paul Savage

Beilstein J. Org. Chem. 2012, 8, 606–612, doi:10.3762/bjoc.8.67

• -substituted or 1,1-disubstituted alkenes the regiochemistry of the nitrile oxide cycloaddition followed the expected outcome in which the oxygen of the nitrile oxide became attached to the more substituted end of the double bond [41]. This regiochemical orientation was established from the 1H NMR chemical