A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• tertiary amines (1.467(2) and 1.476(2) Å), resulting in a slight distortion of the ring and nitrogen plane. Conclusion We have described an operationally simple synthetic procedure for the N-tetraalkylation of cyclam (1) and cyclen (2) with a range of hydrophobic functional groups. This procedure affords

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• this process apparently plays the Rh-complex, since it is known that without a catalyst a cleavage of tertiary amines of this kind in the presence of oxygen does not occur [30]. It is conceivable as an alternative that the occurrence of amide 7 is derived from the oxidation of the Wolff rearrangement

Potent triazine-based dehydrocondensing reagents substituted by an amido group

• Munetaka Kunishima,
• Daiki Kato,
• Nobu Kimura,
• Masanori Kitamura,
• Kohei Yamada and
• Kazuhito Hioki

Beilstein J. Org. Chem. 2016, 12, 1897–1903, doi:10.3762/bjoc.12.179

• (NMM). Related triazinylammonium salts (DMT-Am) can be prepared from other tertiary amines 5 instead of NMM (Scheme 1c) [6]. Since the direct reaction of carboxylates with CDMT is very slow, the formation of DMT-Am is essential for the conversion of carboxylates into 4 [7]. Therefore, we developed

• catalytic amide-forming reactions in water using triazinylammonium salts (DMT-Am) generated in situ from CDMT and a catalytic amount of tertiary amines 5 (Scheme 1d). Most notably, by introducing various functional groups into 5, it was possible to develop a cyclodextrin-based artificial acyltransferase [7

• recognitions of carboxylic acids were affected by fuctionalized DMT-Am. However, once the reaction with 1 takes place, the functionalized tertiary amines 5 liberated, no longer affect the following reaction (Scheme 1d). As a consequence, the resulting acyloxyatriazine intermediate 4, which is the same

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• methanol, an alternative route involving the reaction of 6-bromohexyl D-glucopyranoside (2′ [32] or 3′) with tertiary amines (trimethylamine in ethanol and with pyridine) was applied; the yields were of 90–94%. Shifting the pyranose leaving group (halogen) by six carbon atoms from C1 makes it easier to

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• -workers explored the ability of chiral tertiary amines to catalyze the enantioselective addition of thiols to α-aminoacrylates (Scheme 5) [22]. The authors found that quinidine (21) catalyzed the enantioselective addition of benzylmercaptan (19) to α-aminoacrylate 20 in modest enantioselectivity

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• diastereoisomeric tetrahydrothiophenes were observed when using tertiary amines such Et3N, DBU or TMG [21][22]. At the outset, the sulfa-Michael/nitroaldol reaction was studied by reacting trans-β-nitrostyrene, (E)-1-phenyl-2-nitropropene and (E)-1-phenyl-2-nitrobutene in toluene at room temperature with 1,4

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

• associated with adding two different nucleophiles and simultaneously eliminates the need for an external oxidant. Particularly advantageous is the direct addition of electron-rich amino groups, especially tertiary amines, which are difficult to access by other known methods. Furthermore, O-acylhydroxylamines

• variety of 1,2-oxyamino products in a modular manner with excellent regioselectivity. It offers an appealing oxyamination method, especially for the construction of electron-rich tertiary amines. Future efforts will be undertaken for a better understanding of the reaction mechanism and for the development

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

• ] reported the copper-catalyzed, tert-butyl hydroperoxide (TBHP)-assisted C–H amidation of tertiary amines 1. By heating at 80 °C, the C–H bond in dimethylaniline underwent direct amidation to provide products 3 in the presence of amides 2. On the other hand, the dephenylation transformation via C–C bond

• from the chemistry related to the C–H amidation. Copper-catalyzed C–H amidation of tertiary amines. Copper-catalyzed C–H amidation and sulfonamidation of tertiary amines. Copper-catalyzed sulfonamidation of allylic C–H bonds. Copper-catalyzed sulfonamidation of benzylic C–H bonds. Copper-catalyzed

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• 1,2-diazine or imine co-reactants to yield functionalized hydrazones or benzylanilines. SCPC with tertiary amines enabled electron-deficient alkenes to be alkylated and furoquinolinones to be accessed. Primary amines on their own led to self-reactions involving C–N coupling and, with terminal diamines

• donor precursors Hoffmann and co-workers demonstrated that tertiary amines N(CH2R)3 were suitable donors, transferring their N-lone pair electrons to photoexcited TiO2, CdS or ZnS thus generating aminium radical cations +•N(CH2R)3. These deprotonated at an adjacent C-atom to furnish α-aminoalkyl

• isolated in a good yield but the process was less effective with 6- and 7-membered rings (Scheme 4). When the water in these amine reactions was replaced by alcohols, photolyses with Pt-TiO2 led to coupling and the formation of the corresponding secondary or tertiary amines; for example 20 (Scheme 4) [49

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• corresponding acetylated (hetero)arenes which are easily accessible reagents, including commercially available ones. It is well known that the reaction of isatins 7 with methyl ketones 8 leads to the formation of aldol-type adducts 9 under catalysis with mild bases, such as secondary or tertiary amines. These

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

• tetrasubstituted enamines. The use of the sustainable and environmentally benign solvent (R)-limonene for the reaction is also reported with the amine isolated by acid extraction. Keywords: alkenes; homogeneous catalysis; hydrogenation; renewable solvents; tertiary amines; Introduction A potentially very direct

• method to produce tertiary amines is by the hydrogenation of enamines. While the hydrogenations of enamides, bearing coordinating acyl substituents is probably the most developed and studied of all hydrogenation processes, studies on the hydrogenation of unactivated enamines are scarce and several

• triacetoxyborohydride or sodium cyanoborohydride can be appealing at small scale where the practical issues noted above are not so important. However, the formation of tertiary amines from aryl ketones using hydride reagents has been reported to be problematic [31]. In addition, the hydride reductions, whether carried

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• the area of visible light photoredox reactions. Visible-light-induced sp3 C–H bond functionalization of tertiary amines. Substrate scope for aerobic oxidative cyclization of N,N-dimethylanilines with maleimides. A proposed reaction mechanism. Screening and control experimentsa. Optimization of

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• 10.3762/bjoc.10.316 Abstract Nucleophilic trapping of iminium salts generated via oxidative functionalisation of tertiary amines is well established with stabilised carbon nucleophiles. The few reports of organometallic additions have limited scope of substrate and organometallic nucleophile. We report a

• demonstrated the former reason herein, investigation of the latter is underway to extend the substrate scope beyond benzylic tertiary amines. Examples of biologically active 1,2-disubstituted tetrahydroisoquinolines. Products from allylzinc reagent addition to 5a and 5b. Proposed mechanism for formation of

Synthesis of nanodiamond derivatives carrying amino functions and quantification by a modified Kaiser test

• Gerald Jarre,
• Steffen Heyer,
• Elisabeth Memmel,
• Thomas Meinhardt and
• Anke Krueger

Beilstein J. Org. Chem. 2014, 10, 2729–2737, doi:10.3762/bjoc.10.288

• to primary amines. Secondary amines cannot be detected reliably and aromatic and tertiary amines do not yield positive test results either [24]. One report on the non-quantitative application of the Kaiser test on ethylene diamine functionalized nanodiamond has been reported recently [25]. For

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• influence of the anion on the nature of the coordinative bond. In the case of tertiary amines (e.g., PEG150MeBu2N), all the protons shifted downfield after forming the chelated IL with LiNTf2. Changing the anion to CF3SO3− had negligible influence on the coordination ability. All the neutral ligands shown

• -philic nature of the PEG chain facilitates CO2 sorption. Generally, anhydrous tertiary amines absorb CO2 only under high CO2 pressures to form instable zwitterionic alkylcarbonate salts (Table 1, entry 9) [42]. [PEG150MeBu2NLi][NTf2] and [PEG150MeBu2NLi][SO3CF3] were able to rapidly reach 0.66 and 0.61

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• to polymer backbones and side groups, including the addition of tertiary amines and pyridine (all analogues tested were insoluble) [91] and siloxanes (poly(dimethylsiloxane) (PDMS, Table 2, compound 24)), which has the highest solubility of all known non-fluorinated polymers in carbon dioxide [85][86

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• palladium as a catalyst in the presence of tertiary amines as base. A variety of hydrophilic phosphines (102, 103) was synthesized. Since no protective groups were introduced, the method proves to be compatible with several functionalities. This methodology or in a slightly modified form has been used by

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

• 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

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• case of ND, for example, basic polypeptides [16], polyamine polymer [17], primary and tertiary amines [17][18], and quaternary ammonium salts [19] were employed to coat ND covalently or noncovalently as positively charged ligands for DNA immobilization. Although the functionalized ND is proven to

Continuous-flow Heck synthesis of 4-methoxybiphenyl and methyl 4-methoxycinnamate in supercritical carbon dioxide expanded solvent solutions

• Phei Li Lau,
• Ray W. K. Allen and
• Peter Styring

Beilstein J. Org. Chem. 2013, 9, 2886–2897, doi:10.3762/bjoc.9.325

• . Among them, tertiary amines such as triethylamine (Et3N), tributylamine (Bu3N) and alkali salts like carbonates, acetates or phosphates play crucial roles [7]. Solubility of the base and its basicity in the appropriate solvents are criteria that need to be considered. Traditionally, most Heck reactions

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• ], and fulfil the twofold role of base and ligand in organic solvents [90][91][92][93][94][95][96][97]. Although a variety of other tertiary amines such as propylamine [98][99] or tributylamine [100] has been employed, there is no comprehensive study about the influence of the nitrogen substituents. The

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• aromatic amino acid residues, Tyr652 and Phe656, that are located in an exposed area within the S6 domain pointing towards the possibility of cation π-interactions explaining the affinity of drugs containing tertiary amines towards hERG channels. Consequently, careful and early-stage examination of hERG

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

• ion is subsequently reduced to α-amino radical 132 by Ru(I). Back in 1986, the Whitten group established this pathway by irradiation of three substituted tertiary amines with Ru[4,4’-CO2Et(bpy)]3(PF6)2 respectively using visible light (Scheme 29) [101]. The identity of carbon radicals 130a and 130b

• azodicarboxylates. α-Arylation of amines. Plausible mechanism for α-arylation of amines. Photoinduced C–C bond cleavage of tertiary amines. Photoredox cleavage of C–C bonds of 1,2-diamines. Proposed mechanism photoredox cleavage of C–C bonds. Intermolecular [3 + 2] annulation of cyclopropylamines with olefins

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• , which contains two tertiary amines and is readily obtainable by an acid-promoted hydride shift process [52][53][54], was also exposed to oxidative conditions (Scheme 1, reaction 2). We had hypothesized that quinazolinone 32 might be formed in this reaction by the debenzylation of an intermediate iminium