Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• amination of ortho positions: synthesis of carbazoles Although a handful of methods for the construction of carbazoles, which are biologically important, is available in the literature, these procedures suffer from the need for an elevated temperature and the requirement of stoichiometric amounts of strong

• oxidants [151][152][153]. To overcome these drawbacks, recently, Cho’s group synthesized carbazole derivatives using a dual photoredox-catalyzed intramolecular C−H bond amination of N-substituted 2-amidobiaryls with photoredox catalyst 14 in presence of Pd(OAc)2 as a cocatalyst under aerobic conditions

• radioactivity in the product in percent compared to the initial value. C–H amination Aerobic aminations by acridinium catalysis: In 2015, Nicewicz and his team established a method for arene aminations using photocatalyst 3a, 3,6-di-tert-butyl-9-mesityl-10-phenylacridinium tetrafluoroborate, to generate a

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

• Pedro H. P. R. Carvalho,
• Jose R. Correa,
• Karen L. R. Paiva,
• Daniel F. S. Machado,
• Jackson D. Scholten and
• Brenno A. D. Neto

Beilstein J. Org. Chem. 2019, 15, 2644–2654, doi:10.3762/bjoc.15.257

•  1. The new fluorescent structure is accessible in a two-step procedure from the commercially available 4-bromo-2,1,3-benzothiadiazole (BTD-Br) and 4-aminopyridine (4AP), as we have recently described [41]. The Buchwald–Hartwig amination protocol afforded the fluorescent BTD-4AP in 80% yield after

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• -position, was also tested since this atom type provides full agonist activity of parent 1d. The synthesis of the compounds 2a–e was performed according to the strategies depicted in Scheme 1. The intermediate 7 was prepared as described previously by us [28] and was used in a reductive amination with 4

• performed following the strategies shown in Scheme 1 as disclosed for compounds 2a–e. Briefly, a reductive amination of 7 and 8b gave nitro compound 9b, which after reduction to 10b, coupling with nitroso compounds 11a–e to 13a–e and methylation gave iodide salts 3a–e with purities of trans-isomers ≥99% and

• was selectively reduced with DIBAL-H to benzyl alcohols 23f–h, which were oxidized with Dess–Martin periodinane to the corresponding benzaldehyde 26f–h. Reductive amination of 26f–h with 7 gave the tertiary amines 13f–h. Methylation with iodomethane and subsequent precipitation gave 3f–h as orange

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• trifluoroacetate 60 by a known electrophilic substitution procedure that was developed by Tahara and co-workers [64]. Curtius rearrangement of 60 gave an isocyanate intermediate, which was reduced with LiAlH4 followed by reductive amination affording tertiary amine intermediate 61. Oxidation of 61 to its

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• inhibitors. When the aziridine-aldehyde (2R,1'R)-6 was subjected to the reductive amination with 4 dipeptides secondary amines 172 (a R' = iBu, R''= sec-Bu; b R' = R'' = iBu; c R' = sec-Bu, R'' = iBu; d R' = R'' = sec-Bu) were produced (Scheme 44) [101]. In the presence of triphosgene a series of imidazolin

• biological activities [106]. (−)-Dihydropinidine (2S,6R)-187a, isosolenopsin (2S,6R)-187b, and isosolenopsins A (2S,6R)-187c and B (2S,6R)-187d were synthesized as hydrochloride salts from the aldehyde (2S,1'R)-6 applying a reductive amination as a key step (Scheme 50) [33]. To this end the aldehyde (2S,1'R

• form a cis-2,6-disubstituted piperidine framework in (2S,3R,6S)-197. N-Methylation of (2S,3R,6S)-197 was accomplished by reductive amination while a selective deprotection provided the hydroxymethyl group in (2S,3R,6S)-198. Swern oxidation, Julia–Kocienski olefination and desilylation gave (−)-(2S,3R

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• widely described in the literature encompassing a number of reactions like oxidative cyclizations [11], oxidative coupling reactions [12], Vilsmeier type cyclizations [13], intramolecular aminooxygenation/C–H amination reactions [14][15], Groebke–Blackburn–Bienayme (GBB) reactions [16][17][18] and many

• -catalyzed cross-coupling reactions have laid down the foundation of new C–C bond formations [50][51]. A number of Pd-catalyzed organic reactions viz., C–N coupling, amination and intramolecular amidation, cyclization, and Suzuki–Miyaura coupling [52][53][54][55] have recently been reported in the literature

• –Villiger reactions, epoxidations of alkenes, intramolecular ring expansions, hydroaminations, and amination reactions and carbonyl–ene reactions for the formation of C–C bond. Scandium-catalyzed reactions represented remarkable enantioselectivities [79][80][81]. Recently the group of Rani has developed fly

Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene

• Alberto Abengózar,
• David Sucunza,
• Patricia García-García and
• Juan J. Vaquero

Beilstein J. Org. Chem. 2019, 15, 1257–1261, doi:10.3762/bjoc.15.122

• -phenanthrene 1a [23]. Thus, an initial Buchwald–Hartwig amination between 2-bromo-5-chlorostyrene and 3-butenylamine was the initial step. This coupling was performed at 70 °C, as a higher yield was obtained at this temperature (71% at 80 °C, 24 h vs 82% at 70 °C, 48 h). Substrate 2 was then cyclized with

• reactions of 1b, under conditions optimized for a related BN-benzo[c]phenanthrene [30]. Gratifyingly, Suzuki coupling and Buchwald–Hartwig amination yielded the corresponding aryl- and amino-substituted BN-phenanthrenes 1c and 1d in good yields (Scheme 2). Moreover, Sonogashira couplings efficiently proceed

A three-component, Zn(OTf)₂-mediated entry into trisubstituted 2-aminoimidazoles

• Alexei Lukin,
• Anna Bakholdina,
• Anna Kryukova,
• Alexander Sapegin and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2019, 15, 1061–1064, doi:10.3762/bjoc.15.103

• turned our attention to propargylureas 4. These have been previously converted to the respective 2-imidazolones via base-promoted intramolecular amination of the propargyl group [5][6]. However, such transformations have not been studied under transition metal or Lewis acid catalysis. Moreover, the

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• -alkylation of the heroin domain via reductive amination. For the remaining drug–haptens, the use of repeated amide bonds naturally led us to employ EDC-mediated coupling to join the heroin and fentanyl domains. For the sake of brevity, detailed synthetic procedures, and structures of all intermediates can be

• found in Supporting Information File 2. Heroin domain syntheses All nine haptens in the series were constructed from one of the three heroin intermediates shown in Figure 3. Haptens to be prepared via reductive amination (HF-1, HF-2, HF-4, Figure 2 yellow background) required the secondary amine form

• tert-butyl ester protected derivative 4 of the commercially available 4-(4-aminophenyl)butanoic acid was accessed via protection and deprotection of the amine with a phthaloyl group (intermediates 2, 3). Reductive amination of 4 with commercially available phenethylpiperidin-4-one furnished

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• by X-ray photoelectron spectroscopy (XPS). This residue was introduced by reductive amination of the DAT scaffold with the respective benzaldehyde derivative. In one compound (60% yield over three steps) the ALA unit is directly bound to the DAT as a relatively electron-withdrawing amide. In solution

• accessed in three steps from diethyl succinate according to Wu et al. [41]. Reductive amination with trifluoromethylated benzaldehyde was accomplished with a mixture of ZnCl2 and NaBH3CN [42] yielding the respective N-benzylated compound 2 in good yield. After subsequent N-Boc-deprotection with TFA

• electronically decoupled by introduction of a propylene spacer. Therefore, we started the synthesis with compound 5 (Scheme 2), which was accessed from compound 1 in two steps by reductive amination with N-Alloc-3-aminopropanal and subsequent N-Boc deprotection as reported recently [44]. Reductive amination with

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• obtained as a diastereomeric mixture via an Ugi–Nenajdenko reaction using the 4-methyl-2,6,7-trioxabicyclo[2,2,2]octyl (OBO) ester 46 to avoid epimerization of the isocyanide, followed by a reductive amination and chromatographic separation of the isomers; a Passerini–Dömling IMCR led to the heterocyclic

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• evaluated in several enantioselective reactions, specifically in the asymmetric allylic amination (AAA), which showed a promising enantiomeric excess of up to 75% ee. Furthermore, a new disubstituted α-CD catalyst was prepared as a pure AD regioisomer and also tested in the AAA. Our results indicate that (i

• disubstituted CD derivatives performed similarly to monosubstituted CDs. Therefore, these new CD derivatives with cinchona alkaloids effectively catalyze asymmetric allylic aminations and have the potential to be successfully applied in other enantioselective reactions. Keywords: asymmetric allylic amination

• asymmetric allylic amination (AAA). We successfully prepared a series of monosubstituted α- and β-CDs derivatives with the cinchona alkaloids cinchonine, cinchonidine, quinine, and quinidine with up to 95% isolated yield through CuAAC click reactions. By this simple, high-yielding and quick method we

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• -Chloro- and 2-bromocyclohexanone were synthetized as previously described [38][39], to provide cis-2-chloro (Cl) and cis-2-bromocyclohexylamine (Br), respectively, by a reductive amination [40]. To a sealed tube were added the corresponding ketone (10 mmol), ammonium acetate (100 mmol) and sodium

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• (or amination) sequence on achiral nonfunctionalized cyclopropenes provided the desired cyclopropanol (and cyclopropylamine) derivatives in excellent diastereo- and enantiomeric excesses. Keywords: carbocupration; cyclopropanol; cyclopropene; regioselectivity; stereoselectivity; Introduction The

• enantiomeric ratios (er up to 99:1, Scheme 7). Following the same concept of copper-catalyzed diastereo- and enantioselective carbomagnesiation reaction of cyclopropenes 6 followed now by a selective electrophilic amination reaction, a powerful entry to cyclopropylamines as single diastereoisomer and in

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• -hydroxyacrylamides for the construction of indolizinones via sequential C(sp2)–H activation and C(sp3)–H amination has been developed. This approach shows excellent functional-group tolerance. The synthesized scaffold forms the core of many natural products with pharmacological relevance. Keywords: annulation; C–H

• (Scheme 1b) [29][30][31]. Inspired by this work, we envisaged that tricyclic indolizinones could be built through rhodium(III)-catalyzed sequential C(sp2)–H activation and C(sp3)–H amination of O-substituted N-hydroxyacrylamides (Scheme 1c). Results and Discussion We selected N-hydroxyacrylamide 1a as our

• , we have developed a rhodium(III)-catalyzed sequential C(sp2)–H activation and C(sp3)–H amination of O-substituted N-hydroxyacrylamides for the synthesis of indolizinones. This method shows excellent functional-group tolerance. The family of indolizinone products represents potential bioactive

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• (1R,3S)-HPA-12 (2) used the chiral pool approach [15][16], crystallization-induced asymmetric transformation [17], diastereoselective reduction of γ-aryl-γ-oxo-β-amino alcohol [18], cycloaddition of oxime with alkenes [19], enantioselective carbonyl reduction followed by an organocatalyzed α-amination

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• indole moiety to afford the target product 64 along with the regenerated Rh(III) catalyst. A silver-catalyzed intramolecular cascade amination/ring-opening/cyclization of a variety of substituted MCPs 69 was proposed by Fan and co-workers, which provided a simple and efficient way for the building of

• -tethered alkylidenecyclopropanes). Rh(II)-catalyzed oxidative radical ring-opening and cyclization of MCPs. Ag(I)-catalyzed oxidative radical amination/ring-opening/cyclization of MCPs derivatives. Heating-promoted radical ring-opening and cyclization of MCP derivatives (arylvinylidenecyclopropanes) with

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• and in particular compounds with an amino functional group such as 3-aminopiperidine are valuable intermediates for the production of a large number of bioactive compounds with pharmacological properties. In this paper, the synthesis of both enantiomers of 3-amino-1-Boc-piperidine by amination of the

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence. Keywords: 2-aminochromene; domino reaction; imidazo[1,2-a]pyridine; 2-iminochromene; Michael addition; multicomponent reaction; oxidation; pyridine amination; Introduction Domino reactions are well

• reaction (Table 1, entry 10). The use of KMnO4 which is known as a classical oxidant for pyridine amination [46], gave desired chromenoimidazopyridine 5a with admissible 47% yield (Table 1, entry 11). The yield of 54% was achieved with Mn(OAc)3·2H2O (Table 1, entry 12), while increasing the reaction time

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• Hoveyda–Grubbs second-generation (HG-II) catalyst to deliver the corresponding dihydropyrans 16 in excellent yields given that this kind of reaction can be sensitive to the substitution pattern contained in the substrate [11]. After silyl deprotection, the key C–H amination precursors 17a,b for the

• literature [7][8]. Although the intramolecular C–H amination of compounds 17 under the Du Bois conditions [24] was already described in the literature [8][9], the reaction was nevertheless achieved with carbamate 17a in order to check the reproducibility of the final step. As expected, L-vancosamine glycal 1

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• % yield in 17 steps from 16. The pyrrolidine nitrogen was then further derivatized with several small substituents (Scheme 7). Reductive amination with several aldehydes resulted in 3a–c. The N-methyl analogue 3d was synthesized via methylation with MeI. The methanesulfonamide 3e and acetamide 3f, in

Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles

• Takashi Go,
• Akane Morimatsu,
• Hiroaki Wasada,
• Genzoh Tanabe,
• Osamu Muraoka,
• Yoshiharu Sawada and
• Mitsuhiro Yoshimatsu

Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250

• yields. Corresponding pyrroloselenides 6a–f were prepared by applying a similar synthetic sequence; however, the selenoxides could not be obtained by implementing the usual reaction conditions. The structure of the products derived from the amination–cyclisation reaction of sulfanyl 1,6-diyne 1a was

• 1,7-Se shift reactions by investigating the synthesis of pyrroloazepines through amination–cyclisation of 1,6-diynes, followed by the Pummerer reaction and TBAH hydrolysis. We are now investigating the syntheses of pyrroloazepines using 4-heteroarylmethyl-3-sulfanylpyrroles, which could be easily

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• -known biologically active analogs (Scheme 5) [3]. Pd-catalyzed reactions were effected on bromotriazolochromene 5e. The piperazin-1-ylchromenes have been identified to be potent inhibitors at the 5-HT1A receptor and at the 5-HT transporter [45][46]. Thus, Buchwald–Hartwig amination of 1-phenylpiperazine

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• reagents can be used as electrophilic or radical amination agents in a wide range of reactions [14]. In the present study, we opted to evaluate the addition of N-alkyl-N-chloramines with (a) alkenes to produce amines, (b) aldehydes to give amides, (c) reaction with a base to afford imines. Several alkenes

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• protected naturally occurring amines such as GABA and phenylethylamine as well as diamines with orthogonal protecting groups, cf. product 2c. The combination of this protocol with the diastereoselective reductive amination reported by Hughes and Devine [41], provides access to very high value chiral α

• , as well as aliphatic chains. Unsurprisingly, esters and other base labile groups are not encountered. A recent publication by König and his group shows the DDQ catalysed (3DDQ Ered*(cat/cat•−) ≈ +3.18 V vs SCE) C–H amination of arenes and heteroarenes using weakly nucleophilic species such as

• (Figure 14) [77]. Nicewicz and co-workers have published a procedure for the aerobic C–H amination of aromatics, using acridinium salts as the photocatalyst under blue LED irradiation (Scheme 32) [78]. The authors have demonstrated a truly extensive scope for their protocol, subjecting a range of