First chemoenzymatic stereodivergent synthesis of both enantiomers of promethazine and ethopropazine

• Paweł Borowiecki,
• Daniel Paprocki and
• Maciej Dranka

Beilstein J. Org. Chem. 2014, 10, 3038–3055, doi:10.3762/bjoc.10.322

• derivatives by means of PBr3, and subsequently reacted with appropriate amine providing desired pharmacologically valuable (R)- and (S)-stereoisomers of title drugs in an ee range of 84–98%, respectively. The modular amination procedure is based on a solvent-dependent stereodivergent transformation of the

• subsequently proceeded amination with Et2NH and Me2NH, respectively. In all cases, a sealed glass vessel was used since these reactions need to be operated mostly at elevated temperatures, and low-boiling amines (bp. in the range of 54–60 °C) could be lost in the course of the process. The first set of

• -BuLi were applied it led only to exhaustive decomposition of the starting material (±)-8 producing a complex mixture. To improve the efficiency of the desired process, various catalytic conditions were subsequently evaluated. Initially, we decided to employ PTC-assisted amination in the similar manner

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• second step under the catalysis of Pd(OAc)2 comprised both cyclisation and oxidation in a single step: a dehydrogenative C–H amination with PhI(OAc)2 as oxidant and removal of the picolinamide group followed by oxidation with Cu(OAc)2. This strategy afforded phenanthridines in moderate to good yields (up

Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolecular [1,5]-hydride shift/isomerization reaction

• Chun-Huan Jiang,
• Xiantao Lei,
• Le Zhen,
• Hong-Jin Du,
• Xiaoan Wen,
• Qing-Long Xu and
• Hongbin Sun

Beilstein J. Org. Chem. 2014, 10, 2892–2896, doi:10.3762/bjoc.10.306

• Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes via intramolcular [1,5]-hydride shift/isomerization reaction has been realized, using the inherent reducing power of 3-pyrrolines. A series of N-arylpyrrole containing amines are obtained in high yields. Keywords

• part of our interest in expanding the inherent reducing power of 3-pyrrolines, we report herein the Lewis acid-catalyzed redox-neutral amination of 2-(3-pyrroline-1-yl)benzaldehydes using the iminium group as the H-shift acceptor (Scheme 1, reaction 3). Notably, this reaction should meet the

• established the optimized reaction conditions using ZnCl2 (5 mol %) as the catalyst and CH2Cl2 as the solvent, and running the reaction at room temperature or under reflux. Under the optimized conditions, the results of the amination reaction of 2a with various 2-(3-pyrroline-1-yl)benzaldehydes 1 are shown in

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

• and dispersion behaviour due to their protic character and the possibility to protonate the nitrogen. In the case of diamond the direct amination of the surface has rarely been reported. Sotowa et al. used the photochemical reaction of ammonia with chlorinated diamond [3]. However, the termination

• carried out using gaseous ammonia and hence the isolation and purification of the reaction product 11 is very simple. As expected the intensity of the sulfone related IR bands decreases upon amination (but does not vanish as only the SO2Me group in 2-position is exchanged) and new signals corresponding to

Oxidative phenylamination of 5-substituted 1-hydroxynaphthalenes to N-phenyl-1,4-naphthoquinone monoimines by air and light “on water”

• Julio Benites,
• Juan Meléndez,
• Cynthia Estela,
• David Ríos,
• Luis Espinoza,
• Iván Brito and
• Jaime A. Valderrama

Beilstein J. Org. Chem. 2014, 10, 2448–2452, doi:10.3762/bjoc.10.255

• -(4-hydroxyphenyl)amino-1,4-naphthoquinone (3), prepared by acid-induced amination of 1,4-naphthoquinone with 4-hydroxyphenylamine in ethanol, strongly inhibit the proliferation of cancer cells [11][12]. These stimulating results were obtained by using prostate (DU-145), bladder (T24) and breast (MCF

• (1) and the amination of juglone (2) with 4-hydroxyphenylamine on water were examined separately. It is noteworthy that similar reactions have been recently reported by using a one-flask procedure where juglone 2 was first produced by photoinduced photooxygenation of 1,5-DHN (1) in CH2Cl2/MeOH and

• unexpected but interesting result indicates that on-water oxidative amination reaction of 1,5-DHN (1) with 4-hydroxyphenylamine to produce compound 6 is more favorable than the photooxygenation reaction to give juglone (2). The N-phenylquinone imines are considered as an important class of compounds because

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• to the electrophile compared to the conventionally accepted model [31]. The use of other electrophiles for the stereoselective formation of C–N bonds has also been reported. Thus, α-amino-α-alkyl phosphonic acids [32][33][34] could be obtained through amination and azidation of phosphonamide anions

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• carbonyl group at the termini has been carried out. The carbonyl group has been exploited for the multivalent conjugation to a sample saccharide by reductive amination and alkoxyamine conjugation. Keywords: bis-MPA; carbohydrates; dendrons; levulinic acid; multivalency; multivalent glycosystems

• carbonyl groups can be exploited for carbohydrate functionalization [15][16] by reductive amination, oxime or hydrazone formation to yield suitably functionalized saccharides (Figure 1). Given the relevance of L-fucose in mammal oligosaccharides, α-L-(2-aminoethyl) fucoside [17] and α-O-L

• synthesized from commercial L-fucopyranose in 4 and 5 steps, respectively, as already reported by Flitsch and co-workers [17] and Dumy and co-workers [18]. Dendron conjugation to L-fucose by reductive amination α-L-(2-Aminoethyl) fucopyranoside (4) was conjugated first to G0 dendron 1 by reductive amination

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

• Sebastian Rabe,
• Johann Moschner,
• Marina Bantzi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

• was thought to establish the C-nor-D-homo steroid system, and a gold-catalyzed amination/annulation/aromatization sequence was planned to install the pyridine F-ring. Diazo compound 3 originates from diene 4 through standard transformations, the latter being accessible from commercially available and

• product 13 by chromatography was then achieved after selective hydrogenation of only the exocyclic olefin in 14 (H2, cat. Rh/C, EtOAc, 25 °C, structure of hydrogenation product not shown) employing the mixture of the isomers 13 and 14 from the previous step. Finally, a gold-catalyzed amination/annulation

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• mannose to PEI via a PEG chain spacer (Figure 3B). This system was used to deliver small interfering RNA (siRNA) into a murine macrophage cell line [44]. Mannose residues as their 2-aminoethyl glycosides were attached by reductive amination to the surface of copolymer micelles of PEG with poly-ε

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• ’-diisopropylcarbodiimide (DIC)-mediated acylation with bromoacetic acid, followed by amination with the propargyl amine. After the completion of synthesis, the oligomers were cleaved from the resin using a 4:1 solution of CH2Cl2/hexafluoroisopropanol (HFIP). Macrocyclizations of the linear N-substituted oligoglycines 6–8

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• in the Pd-catalyzed allylic substitution led to excellent regio- and enantioselectivities for a wide range of substrates in both allylic alkylation and amination reactions despite of the electronic properties of the allylic substrates [28][29][30][31][32][33]. Recently, Shen and co-workers reported

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• classical Chichibabin reaction [47], there has been considerable interest shown for the synthesis of these compounds with varying substitution patterns [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. Most of the methods used presynthesized quinolines for the 2-amination via either

• creating initially a leaving group and its subsequent substitution or via activation of the nitrogen atom and direct amination at C-2 while few methods afforded the direct 2-aminoquinoline synthesis from the acyclic precursors. Most recently, we have disclosed a method for the synthesis of E-α,β

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• . However, a complete conversion of 2-bromonitrobenzene was observed. 2-Bromoaniline was found to be unreactive and was recovered. It should be noted that no amination reaction of 2-bromoaniline due to self-coupling was observed. From 2-(trifluoromethyl)bromobenzene, a very similar mixture of regioisomers

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• et al. [95] reports the amination of either triaryl phosphate or dialkyl aryl phosphate catalyzed by nickel organometallic complexes. It is an additional illustration of the use of aryl phosphate, which can be readily obtained by AT reactions. Beside the use of phosphorus species as a substrate in

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• by reductive amination (reactions not displayed), as demonstrated before in our syntheses of simplified muraymycin analogues [21][22]. N-Cbz-protected acid 19 was also used for a methodical study regarding the acylation of the 3-hydroxy group. Therefore, 19 was converted into benzyl ester 23 (70

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

• -iodobenzene (19) and cycloproylamine, 2-bromo-N-cyclopropylaniline (20) was prepared in 75% yield via the Buchwald–Hartwig amination [39][40]. The [3 + 2] annulation of 2-bromo-N-cyclopropylaniline (20) and phenylacetylene (2) was performed using the optimized catalyst system to provide cyclic allylic amine

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• unprotected β-glycopeptides since the equilibrium between hemiacetal and open-chain aldehyde form also does not interfere with the 314-helix secondary structure and allows further functionalization with saccharides, e.g., by reductive amination. Sketch of right-handed β-peptide helix functionalized in every

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• the treatment of multiple myeloma and mantle cell lymphoma [21]. This product is usually synthesized in three representative processes: (1) to use (1S,2S,3R,5S)-(+)-2,3-pinanediol as the chiral auxiliary for the addition reaction followed by chlorination and amination [14][15]; (2) to perform copper

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• 2 equivalents of cinnamyl alcohol 44 in the presence of 2 mol % of Pd/Xanthpos followed by an esterification using benzyl bromide. Ozonolysis, and reductive amination using excess benzylamine in the presence of sodium cyanoborohydride completed the synthesis. Phosphorines Two phosphorines 47a,b were

• . Tandem Kabacknik–Fields/C–N cross-coupling reaction. Tandem Kabacknik–Fields/C-P cross-coupling reaction. Heterocyclization via amide formation. Cyclization via reductive amination. H-Phosphinate alkylation. Cyclization through intramolecular Michael addition. Double Arbuzov reaction of bis

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• R4 was an o-azidobenzene group by a RuCl3 catalyzed C–H amination (Scheme 12, path B). As explained above, A3-MCR is a reaction in which the formation of a metal acetylide and its reaction with an in situ formed iminium cation are the key steps of the process. In the recent literature, there are

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

• separation (washing of a basic aqueous solution of the acids 2) of the two equivalents of BnOH formed during the reductive amination (1→I) proved to be challenging: Due to the high amphiphilicity of carboxylate salts of 2, mixtures in water and an organic solvent tend to form three distinct phases separating

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

• and reductive amination after Boc-deprotection to yield the desired natural product 131 in only five steps. Perhaps one of the most prominent alkaloid syntheses using a DVCPR was carried out by Fukuyama and coworker [118][119][120] and targeted gelsemine (146, see Scheme 17 and Scheme 18), an alkaloid

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

• 1,2,4-trioxalane 191 was synthesized by reductive amination of adamantane-2-spiro-3’-8’-oxo-1’,2’,4’-trioxaspiro[4.5]-decane 190 (Scheme 52). Ozonide 191 is an example of a combination of two known antiparasitic pharmacophores, viz. a peroxide and an aminoquinoline moiety [296]. Arterolane is a fully

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• preliminary report [62]. Thus, reductive amination of Garner’s aldehyde 17 (Scheme 2) with allylamine produced amine 18 which was N-protected with CbzCl to obtain 19 in an overall yield of 89% over three steps. The oxazolidine ring in compound 19 was then cleaved under acidic conditions and the resulting

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• -diaminoquinoline [7]. Another approach is based on the amination of 7-nitroquinoline in position 8 with hydroxylamine under basic conditions. The resulting 8-amino-7-nitroquinoline was reduced with SnCl2·2H2O [8] or hydrazine hydrate on Raney nickel as a catalyst [9] to obtain 7,8-diaminoquinoline. In the last