Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• ; Introduction The photoinduced electron transfer (PET) of an amine to an excited oxidant followed by the loss of a cationic leaving group allows accessing a broad variety of α-aminoalkyl radicals [1][2][3][4]. As first shown by Mariano et al. [5][6] and by Pandey et al. [7] a trimethylsilyl (TMS) group is a

• suitable electrophilic leaving group for this purpose and addition reactions of α-aminoalkyl radicals to double bonds can be induced by irradiation of α-silylated amines in the presence of sensitizers such as 1,4-dicyanonaphthalene or 1,9-dicyanoanthracene. Addition reactions of this type have been broadly

• used for the formation of carbon–carbon bonds [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In non-silylated tertiary amines, a proton can act as a leaving group and photoinduced addition reactions of tertiary amines to enones are long known [23][24][25][26][27][28]. Mechanistically

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• BorDH3 and reference molecules for enzyme assays (5a, 6a, 6b, 7a and 7b); TBS = tert-butyldimethylsilyl, PMB = p-methoxybenzyl, LG = leaving group. Synthesis of the common precursor aldehyde 11. Compound 13 was prepared in six steps and with an overall yield of 40% via a known route by Omura et al. [15

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• corresponding undesired phosphates F). The formation of heterocycles G passing phosphates F through substitution of the phosphate leaving group by the nucleophilic YH moiety would be in principal also a plausible explanation for the formation of F, but can most likely be excluded (see Supporting Information

• other pharmacologically relevant targets on a gram scale. Natural products and other bioactive piperidine derivatives of type B. Retrosynthetic analysis of piperidines B (X = OH or leaving group, PG = protecting group). Synthesis of the protected amino acids 2. (a) KOH for 1b. b) PG–X = Cbz–Cl (1a–c

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• THF in the presence of EDCI and DMAP. The corresponding amides 2–5 were obtained in excellent yields (Scheme 2). The results are shown in Table 1. Preparation of N-substituted N-triazinylpent-4-ynamides The nucleophilic substitution of the methylsulfonyl leaving group from 1 by the lithium salt of

Cyclic phosphonium ionic liquids

• Sharon I. Lall-Ramnarine,
• Joshua A. Mukhlall,
• James F. Wishart,
• Robert R. Engel,
• Alicia R. Romeo,
• Masao Gohdo,
• Sharon Ramati,
• Marc Berman and
• Sophia N. Suarez

Beilstein J. Org. Chem. 2014, 10, 271–275, doi:10.3762/bjoc.10.22

• different from those of the cyclic ammonium NTf2 ILs, which is similar to the situation of linear alkyl quaternary cation ILs [11]. In some instances where the anion is nucleophilic, such as with dicyanamide [12], or the leaving group is resonance-stabilized, such as a benzyl radical [10], the phosphonium

Substrate dependent reaction channels of the Wolff–Kishner reduction reaction: A theoretical study

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2014, 10, 259–270, doi:10.3762/bjoc.10.21

• the former is a typical E2 reaction. The 1-phenylethyl anion is the leaving group at the trans nucleophilic elimination. Thus, the carbanion is formed owing to the delocalization of the negative charge into the phenyl ring. The intermediate is shown in XIVPh (Figure 6). It is noteworthy that the H(14

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• to continue the synthesis with both diastereomers as this elimination is expected to proceed faster in syn-substituted β-alkoxy esters since the hydrogen and the leaving group are in an antiperiplanar arrangement. Continuing the synthesis with the 1S-isomer (Scheme 12), reduction of the ester moiety

• , desilylation, oxidation and esterification (Scheme 14). Attempts to rearrange 93 under the optimized conditions were again unsuccessful. As expected, elimination of the OMOM group during the reaction was not detected due to the unfavoured orientation of the hydrogen and the leaving group. Subsequent acidic

• ]-sigmatropic rearrangement for formation of the C9–C10 bond. R = Me or CO2H, LG = leaving group. Retrosynthetic analysis of the B-seco limonoid scaffold employing a Claisen rearrangement as key step for formation of the C9–C10 bond. PG = protecting group, LG = leaving group. Synthesis of alcohols 19, 20 and 22

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

• -protected alcohol 152. Addition of methyllithium at low temperature [133] resulted in stereoselective conjugate attachment of the required methyl group. Deprotection of the alcohol and transformation into a suitable leaving group yielded tosylate 153. Next, the furan was cleaved oxidatively, the resulting

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• bivalent derivatives. Installation of a leaving group on hydroxymethyl compound 4, for instance, would permit coupling with diverse N-dealkylated opiate scaffolds. Alternative attachment points would also be worth exploring, such as the C-17 lactone, which tolerates reduction and alkylation [1]. As noted

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

• -based electrophilc activation of the C=C, with consequent nucleophilic attack by the ylidic carbon onto the internal carbon of the double bond. Finally, the intermediate lactone 92 underwent cyclopropanation, delivering SPh2 as a leaving group (Scheme 24b). 5 Addition to allylic alcohols The use of

• favoured. Interestingly, a strong hydrogen bond was established during the catalytic cycle between the hydroxy groups. The H-bond turned out to be a key interaction for the high reactivity of 94 toward cyclization, leading to an intramolecular proton transfer resulting into a better leaving group

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

• trifluoromethylation of vinyl(het)arenes at the terminal carbon [83]. The reaction actually proceeded by oxytrifluoromethylation of the vinyl group, followed by elimination of the oxygen-leaving group in the presence of p-toluenesulfonic acid (Scheme 6). Similarly to the Pd-catalyzed C–H trifluoromethylation of

Triol-promoted activation of C–F bonds: Amination of benzylic fluorides under highly concentrated conditions mediated by 1,1,1-tris(hydroxymethyl)propane

• Pier Alexandre Champagne,
• Alexandre Saint-Martin,
• Mélina Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2013, 9, 2451–2456, doi:10.3762/bjoc.9.283

• fluoride as a leaving group in nucleophilic substitution reactions of activated alkyl fluorides through hydrogen bonding [17]. Particularly, water was used as the hydrogen bond donor and co-solvent. DFT calculations show that activation proceeds through stabilization of the transition-state structure by

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• complex as a leaving group, giving rise to the formation of the nitrile oxide. The 1,2,4-oxadiazole moiety is established by the 1,3-dipolar cycloaddition of nitrile oxide to the 4-aminobenzonitrile. However, the Lewis acid might also be involved in the formation of the heterocycle via a Lewis acid

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• installation of a suitable leaving group sets the stage for the introduction of the first silylacetylene. Four different terminal alkynes 21 (a: Si = TMS; b: Si = SiMe2Ph; c: Si = SiMe2Bn; d: Si = Si(iPr)2H) were employed. Best results with yields of over 80% were obtained by the use of acetylene 21a

Gold-catalyzed glycosidation for the synthesis of trisaccharides by applying the armed–disarmed strategy

• Abhijeet K. Kayastha and
• Srinivas Hotha

Beilstein J. Org. Chem. 2013, 9, 2147–2155, doi:10.3762/bjoc.9.252

• oxophilicity of gold salts were observed to be major impediments for the synthesis of oligosaccharides. In order to overcome this problem, a systematic investigation of various leaving groups that bear an alkynyl moiety was carried out. The aim was to find a better leaving group, which would facilitate the

• , armed mannosyl donor 15j reacted with aglycon 19 in the presence of 5 mol % each of AuCl3/AgSbF6 in CH3CN/CH2Cl2 (1:1) at 25 °C for 4 h to give 1,2-trans menthyl mannoside 20. The leaving group 21 could be removed easily by applying high vacuum. Disarmed donors 18a and 18b failed to react with menthol

Synthesis of enantiomerically pure N-(2,3-dihydroxypropyl)arylamides via oxidative esterification

• Akula Raghunadh,
• Satish S More,
• T. Krishna Chaitanya,
• Yadla Sateesh Kumar,
• Suresh Babu Meruva,
• L. Vaikunta Rao and
• U. K. Syam Kumar

Beilstein J. Org. Chem. 2013, 9, 2129–2136, doi:10.3762/bjoc.9.250

• ][4]. In the recent past, synthesis of these chiral building blocks has gained significant interest leading to the publication of many reports. The most common methods include (i) reacting a chiral 1,2-propanediol with a leaving group such as a halide or a tosylate ester in the 3-position with base [5

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

• sizes and acyclic amines underwent the α-arylation reaction to provide benzylic amines. The arylating reagents were benzonitriles substituted with an electron-withdrawing group. The nitrile group functioned as the leaving group. In some classes of five-membered heteroaromatics, a chloride was capable of

• replacing the nitrile group as the leaving group. The authors proposed a mechanistic pathway that is initiated by oxidative quenching of the photoexcited state of Ir(ppy)3 by benzonitrile 121 to generate radical anion 123 and Ir4+(ppy)3 (Scheme 28). Amine 122 is then oxidized to amine radical cation 124 by

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

• chroman 8 (Scheme 2) [13][15][16]. Chan and co-workers have previously proposed that the Friedel–Crafts mechanism could involve the activation of the allylic alcohol by the gold catalyst to turn the hydroxy group into a better leaving group [73]. The observed regioselectivities is then due to the

• ) catalysts are known to coordinate to alcohols [80], in this case turning the hydroxy group into a better leaving group (I), as previously suggested by Chan [73]. Attack at the less hindered position could occur either directly on I [SN2' shown, but in the case of γ,γ-disubstituted substrates (e.g. 19 and 20

The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives

• André S. Kelch,
• Peter G. Jones,
• Ina Dix and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 1705–1712, doi:10.3762/bjoc.9.195

• better leaving group, e.g. bromine as in Scheme 7. After trying numerous different protocols (Br2 addition, NBS in different concentrations and in different solvents, 1,3-dibromo-5,5-dimethylhydantoin) [14] we finally found that excess NBS (6 equivalents) and refluxing in tetrachloromethane at 80 °C gave

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• used. A possible mechanism of this reaction is given in Scheme 7. Double silylation leads to the formation of a good leaving group and the highly electrophilic benzylic carbon is attacked by the nitrile yielding a nitrilium cation. The reaction is finalized by hydrolysis furnishing the carboxamide

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• the trans double bond in the opening of a cyclopropane with an adjacent hydroxy or mesylate leaving group, regardless of the initial configuration of the cyclopropane (Scheme 3, reaction 2) [27]. Braddock has demonstrated that the internal 3,4-E olefin is obtained exclusively in Prins reactions

• stereoselective fashion from displacement of a leaving group at C10, a means for the selective formation of a syn-1,3-diol at C11 and C13 is required. Rychnovsky has demonstrated that alkylation of 4-cyano-1,3-dioxanes (cyanohydrin acetonides) constitutes a practical and valuable approach to syn-1,3-diol

• contain all of the carbon atoms of epoxide fragment 5 in the correct oxidation state. The remaining steps required to access the epoxide consist of acetonide deprotection, displacement of the tosylate or another appropriate leaving group to obtain the terminal epoxide, and silyl protection. Conclusion

Synthesis of the calcilytic ligand NPS 2143

• Henrik Johansson,
• Thomas Cailly,
• Alex Rojas Bie Thomsen,
• Hans Bräuner-Osborne and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 1383–1387, doi:10.3762/bjoc.9.154

• pure (R)-3 in parallel using the method by Marquis et al. [13]. Commercially available glycidol 15 activated as the m-nitrobenzene sulfonyl (m-nosyl) ester 5 has previously been shown to be an ideal leaving group in reactions with aryloxy nucleophiles (e.g., 4) as it promotes direct SN2 over SN2

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• isolated by distillation in a yield of 24%. Reduction of the amount of sodium iodide from 5 to 1.1 equivalents did not result in a more favourable product distribution. The course of this reaction becomes clear in the light of the pseudohalide concept: the thiocyanate functionality acts as a leaving group

Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

• Magnus Liljenberg,
• Tore Brinck,
• Tobias Rein and
• Mats Svensson

Beilstein J. Org. Chem. 2013, 9, 791–799, doi:10.3762/bjoc.9.90

• ) followed by elimination of the leaving group [6]. In the case of attack of anionic nucleophiles (such as MeO−) on fluorinated aromatics, the intermediate σ-complex is anionic and the leaving group is F−, whereas in the case of neutral nucleophiles (such as NH3) the intermediate σ-complex is zwitterionic

• and the leaving group is HF. The departure of H and F can proceed along different mechanisms [7][8][9]. Several methods for predicting local reactivity, or regioselectivity, in SNAr reactions have been reported. Among the earlier ones is the Iπ-repulsion theory based on calculating the fractional

• leaving group was Cl−/HCl or Br−/HBr both for anionic and neutral nucleopiles, because of difficulties in finding relevant σ-complex structures. Instead an approach where we assumed a concerted substitution step and used such transition-state structures gave quantitatively useful results [5]. Recent