Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• . Keywords: copper; electrophilic amination; olefin oxyamination; Introduction The 1,2-oxyamino motif is highly valuable and found in a vast range of biologically active natural products, pharmaceuticals, and agrochemicals (Figure 1) [1][2]. Representative examples include salmeterol (Advair®), a β2

• transformation, integrating an electrophilic amination with a nucleophilic oxygenation, builds upon our recent development in copper-catalyzed olefin difunctionalization, such as copper-catalyzed diamination [40] and amino lactonization [34]. This strategy overcomes common issues of chemo- and regioselectivity

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• -tetramethylpiperidine-N-oxyl (TEMPO) [36]. NFSI is a very interesting reagent. Besides classic electrophilic fluorination reagent [37], it has been used not only as fluoride-atom transfer reagent [38][39][40] but also as nucleophilic/radical amination reagent [41]. We are highly interested in the multiple reaction

• modes of NFSI [37][38][39][40][41], especially as a nitrogen-centred radical. In this context, we have realized copper-catalyzed benzylic sp3 C–H amination [42], aminative multiple functionalization of alkynes [43], diamination, aminocyanation [44] and aminofluorination of alkenes [45], as well as

• amination of allenes [46]. Encouraged by these results, we try to develop copper-catalyzed aminooxygenation of alkenes by using NFSI. Herein, we report a simple and efficient copper-catalyzed three-component aminooxygenation reaction of styrenes with NFSI and N-hydroxyphthalimide (NHPI) derivatives (Scheme

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• encompass asymmetric dihydroxylation of trans-methyl cinnamate or cinnamyl alcohol [6], chiral azetidin-2,3-dione [7], asymmetric C–H amination reactions of a prochiral sulfamate [8], oxazaborolidine reduction of 3-chloropropiophenone or ketone [9], and an imidazolidin-2-one chiral auxiliary mediated

• temperature and dissociated with NaHCO3 to give the primary amine 6 in 90.0% yield. The reductive amination of 6 under Eschweiler–Clarke conditions furnished (S)-dapoxetine 7 with excellent enantiopurity (99.3% ee) in 74.7% yield. After salt formation and recrystallization, the target compound 1 was obtained

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• strategy for the synthesis of diversely functionalized trihydroxypiperidines through double reductive amination of the D-mannose-derived aldehyde 2 (Scheme 1) [24][25]. Among the 1-azasugars accessed with this methodology, our attention was drawn to the enantiomer of natural 3,4,5-trihydroxypiperidine (1

• [24][33]. The versatility of our synthetic methodology allows access to differently substituted N-alkylated trihydroxypiperidines by simply using the same aldehyde and different amines as the nitrogen source in a double reductive amination strategy [24][25]. In particular, catalytic hydrogenation with

• Pd(OH)2/C in MeOH followed by reductive amination of the formed dialdehyde intermediate with 3-azidopropyl-1-amine [34] in the presence of NaBH3CN and AcOH allowed access to N-alkylated piperidine 4 in 67% yield (Scheme 2) [25]. With the key azido intermediate 4 in hands, we proceeded with the

Iron complexes of tetramine ligands catalyse allylic hydroxyamination via a nitroso–ene mechanism

• David Porter,
• Belinda M.-L. Poon and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 2549–2556, doi:10.3762/bjoc.11.275

• ) are established catalysts of C–O bond formation, oxidising hydrocarbon substrates via hydroxylation, epoxidation and dihydroxylation pathways. Herein we report the capacity of these catalysts to promote C–N bond formation, via allylic amination of alkenes. The combination of N-Boc-hydroxylamine with

• area of considerable current research interest [1][2][3][4][5]. The development of methods for catalytic C–H amination has attracted particular attention [6][7][8][9][10][11], given the significance of C–N bonds to the structures of biologically active natural products and pharmaceuticals. In this

• ], manganese- [19][20][21], iron- [23][24], copper- [22][31], rhenium- [26], and rhodium- [27] based reagents. The recent resurgence of interest in the nitroso–ene reaction builds on earlier work by Sharpless, Nicolas, Jørgensen and others. Sharpless reported allylic amination of 2-methyl-2-hexene with N-(p

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• provide the desired protected key intermediate 26 in 90% yield (Scheme 1). To construct the first series of fluorinated purine analogues, compound 26 was treated with a saturated solution of ammonia in methanol, which resulted in the amination at the 6-position and deprotection of the protecting groups to

• broad biological space for this class of nucleoside derivatives. The 2,6-dichloropurine (41) was glycosylated with the 3’-fluororibose intermediate 25 to furnish the 2,6-dichloropurine intermediate 42 in 89% yield (Scheme 4). Chemoselective amination of the 6-position over the 2-position of the purine

• to the cross coupling of monochloro-intermediate 26. From the amination studies of 2,6-dichloropurines, the 6-position of the purine possesses higher reactivity towards nucleophiles than the 2-position. In addition, the selectivity for the 6-position is also higher for the Stille than for the Suzuki

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• -Chloramines provide a versatile and reactive class of reagents for use in electrophilic amination and other reactions. N-Chloro-N,N-dialkylamines have been shown to offer a broad range of products from reactions with i) unsaturated C–C bonds to give amines [1][2][3] and heterocycles [1][4]; ii) Grignard and

Syntheses of 2-substituted 1-amino-4-bromoanthraquinones (bromaminic acid analogues) – precursors for dyes and drugs

• Enas M. Malik,
• Younis Baqi and
• Christa E. Müller

Beilstein J. Org. Chem. 2015, 11, 2326–2333, doi:10.3762/bjoc.11.253

• by oxidative amination of 6 in the presence of solid iodine in aqueous ammonium hydroxide solution (25%) under microwave (MW) irradiation by optimizing a published procedure [62]. Additional amounts of iodine and ammonium hydroxide were needed to drive the reaction towards completion, while attempts

• ) using the same oxidative amination procedure as described above. A total of six equivalents of iodine was needed to produce the desired product 12 in high yield (Scheme 3, Table 1). The method of Gutmann et al. was subsequently applied to the conversion of nitrile 12 to the corresponding 1-amino-2

Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• of diamines and spermine while the CuI/L-proline/EtCN system proved to be preferable for the diarylation of other tri- and tetraamines like spermidine, norspermidine and norspermine. Keywords: amination; aryl amines; aryl iodides; copper catalysis; polyamines; Introduction Natural diamines and

• amines, and a valuable N,N’-diphenylhexane-1,6-diamine was obtained using this catalyst [21]. More traditional and convenient Pd(0)-catalyzed amination, proposed by Buchwald and Hartwig [22][23], was successfully applied in the synthesis of mono- and diaryl-substituted diamines and polyamines in the

• iodides in the copper-catalyzed amination of di- and polyamines providing mainly N-monoaryl derivatives [31]. On the basis of our recent investigations, in order to obtain N,N’-diaryl derivatives, we employed the most suitable catalytic systems, CuI/L-proline (L1) and CuI/2-(isobutyryl)cyclohexanone (L2

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• catalyzed C–H amination reactions, as reported by Warren and co-workers [27][28]. Using this mild copper-catalyzed system, β-arylnitroalkanes were produced in excellent yields (Scheme 3) [16]. The scope of this transformation is remarkably broad with respect to both coupling partners. Electron-rich

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• sulfonamidation of 2-arylpyridines via C–H activation. Besides the peroxide-free advantage, the C–H amination using aniline was found applicable to allow the synthesis of biarylamine. More recently, based on the DG strategy, the Yu group [59] designed the o-amidation of arylamides with copper catalysis under

• underwent C–H amidation with lactams 52 to yield 2-aminoquinoline N-oxides 54 with generally excellent yield. Notably, the catalytic system also allowed a C–H bond amination by using secondary amines 53 for the synthesis of 2-aminoquinoline N-oxides 55. What’s more, the N-oxides could be efficiently reduced

• and benzene C–H bonds. Copper-catalyzed C–H amination/amidation of quinoline N-oxides. Copper-catalyzed aldehyde formyl C–H amidation. Copper-catalyzed formamide C–H amidation. Copper-catalyzed sulfonamidation of vinyl C–H bonds. CuCl2-catalyzed amidation/sulfonamidation of alkynyl C–H bonds. Cu(OH)2

Half-sandwich nickel(II) complexes bearing 1,3-di(cycloalkyl)imidazol-2-ylidene ligands

• Johnathon Yau,
• Kaarel E. Hunt,
• Laura McDougall,
• Alan R. Kennedy and
• David J. Nelson

Beilstein J. Org. Chem. 2015, 11, 2171–2178, doi:10.3762/bjoc.11.235

• NHC·HCl salt, rendering these species highly accessible (Scheme 1b) [10]. After the initial work by Cowley and Jones, various other researchers have disclosed complexes of this form and tested them in cross-coupling reactions such as Buchwald–Hartwig amination [11], Suzuki–Miyaura cross-coupling [12], and

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• alkenes via C–H cleavage is much less known in literature. In 2014, Yu and co-workers [66] reported the cascade synthesis of functionalized pyrrolones 66 via the dual C–H functionalization of α-alkenoylketene N,S-acetals 65. The construction of the products involved the oxidative alkene C–H amination and

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• found to undergo copper-catalyzed aerobic aromatic C–H amination (Scheme 3a) [52] or 1,4-aminooxygenation (spirocyclization) (Scheme 3b) [51], affording phenanthridine derivatives and azaspirocyclohexadienones, respectively, depending on the helical sense of the biaryl axis. Herein we report

A facile synthetic route to benzimidazolium salts bearing bulky aromatic N-substituents

• Gabriele Grieco,
• Olivier Blacque and
• Heinz Berke

Beilstein J. Org. Chem. 2015, 11, 1656–1666, doi:10.3762/bjoc.11.182

• with the preparation of the N1,N2-di(pyridine-2-yl)benzen-1,2-diamine (8). The Buchwald–Hartwig amination was applied in the syntheses of 5 and 6 where 1,2-dichlorobenzene was coupled with aniline and 2,4,6-trimethylaniline, respectively (Scheme 1). Attempting the synthesis of the N1,N2-bis(2,6

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• amination of N-tosylindole aldehyde 6 with 2-iodoaniline (66%), followed by methylation of the aniline nitrogen atom (91%). Substrate 10 with the ester on C2 of the indole was chosen to learn if a more stabilized radical intermediate would still eliminate the N-tosyl group. Reductive amination of 9, 2

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , reduction with LiAlH4, reductive amination and allylation that afforded the indole derivatives 63 (18%) and N-Boc protected compound 68 (23%). The reaction of 63 with Pd(OAc)2 (25 mol %) and tri(o-tolyl)phosphine (55 mol %) at reflux gave 9-endo-64a (24%) and 8-exo-65b (21%). However, the compound 68 under

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ). Conversion of the pendant chloride into iodide 51 was attempted via Finckelstein conditions, however, even when utilising phase-transfer conditions in order to maintain a homogeneous flow regime the outcome was not satisfactory giving only low conversions. Alternatively direct amination of chloride 49

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• , angustureine). However, only two, rather low-yielding procedures for their synthesis are described in the literature. We have developed a simple and efficient protocol for an intramolecular, palladium or copper-catalysed amination of both chloro- and bromo-substituted 3-amino-1,5-diphenylpent-2-en-1-ones

Tuning of tetrathiafulvalene properties: versatile synthesis of N-arylated monopyrrolotetrathiafulvalenes via Ullmann-type coupling reactions

• Vladimir A. Azov,
• Diana Janott,
• Dirk Schlüter and
• Matthias Zeller

Beilstein J. Org. Chem. 2015, 11, 860–868, doi:10.3762/bjoc.11.96

• excess cannot be considered a disadvantage of the method. Additionally, use of the inexpensive Cu(I) catalyst allows to avoid Buchwald–Hartwig amination [24][25], which employs more expensive Pd-based catalysts for a similar type of C–N coupling reactions. In a typical procedure, 1 equiv of MPTTF 7a, 7b

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• obtained through the condensation of aldehyde 3 with mesityldipyrromethane (6) followed by metalation of the intermediately formed free base porphyrin 7 to give its respective zinc complex 2. In the next step, axle precursor 8 was synthesized by reductive amination of 4-bromobenzaldehyde (9) and

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• amination of aldehydes. We now enclose our results on the preparation of related di- and trivalent carbohydrate mimetics in which compounds 1 or 2 are connected to carboxylic acid cores by amide bonds. A series of compounds with spacer units of different length and rigidity were prepared in order to find

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• out as reductive amination or reduction of enamines need stoichiometric acetic acid to promote the formation of the iminium ion that is the substrate reduced in hydride reductions, which might not be compatible with other functional groups. To the best of our knowledge, the hydrogenation of

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• stereoselective preparation of such amines. Throughout the last decades, several strategies [3] such as stereospecific amination via C–H insertion [5][6][7][8] or asymmetric olefin hydroamination [9][10][11][12][13] have been investigated in order to obtain access to optically pure amines. However, the major

• naturally occurring terpenoids is the reductive amination under Leuckart–Wallach conditions (see Scheme 2, pathway I) [39]. This method was applied to convert 2 to N-alkyl substituted menthylamines [40]. However, a significant disadvantage of this method is the lack of stereocontrol and partial inversion of

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• a) [29]. Surprisingly, the same reaction was even more efficient when performed in the presence of the Ti(IV)/Zn/t-BuOOH system (Scheme 2, entry b). Under the latter conditions, the domino approach was also successfully extended to cyclic ethers, promoting the consecutive electrophilic amination to