Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• approaches for the trifluoromethylthio (SCF3) difunctionalization of alkenes, such as cyanation [23], etherification [24][25][26][27], amination [28][29][30], chlorination [31][32], hydrogenation [33], trifluoromethylation [34], phosphonization [35], arylation [36][37][38], trifluoromethylthiolation [39

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products. Keywords: amination; heteroarylation; quinoline N-oxides; regioselective; triazoles; Introduction Quinoline is a key heterocyclic moiety found in many

• ][37][38][39][40][41][42][43][44][45]. For example, Yin and co-workers developed a protocol for the deoxygenative C2-amination of pyridine/quinoline N-oxides using t-BuNH2 and Ts2O/TFA in 2007 (Scheme 1a) [48]. Later, Londregan and co-workers were successful in achieving C2-amination employing

• to amination and amidation, there are few reports on metal-free C2-heteroarylation of pyridine N-oxides. In 1984, Rogers demonstrated the synthesis of 2-triazolylpyridines from 2-azidopyridines and phenylacetylene [51]. Along the same lines, Keith reported methodologies for the C2-imidazolylation and

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and oxidation with sodium periodate, benzyl 2-azido-3-(((benzyloxy)(2-oxoethyl)phosphoryl)oxy)-2-methylpropanoate (69) was obtained. The latter was further transformed to the final phosphonodepsipeptide library 64 after the reductive amination with pyrrolidine derivatives 70 and acylation with a

• the synthesis, diethyl 3,3-diethoxypropylphosphonate (187) was hydrolyzed to 3-oxopropylphosphonate 188, which underwent a reductive amination with benzyloxyamine to give diethyl 3-benzyloxyaminopropylphosphonate (189). After the sequential treatment with acetyl chloride and TMSBr, alkylation with

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• ethers of 3,6-diacetylcarbazole with p-benzoquinone (Scheme 1B) [49], the double Buchwald–Hartwig amination of 4,4'-biphenanthrene derivatives (Scheme 1C) [45] and a enantioselective Fischer indolization–oxidation protocol (Scheme 1D) [43]. Each method is not without drawbacks such as hardly available

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• nitrogen heteroatoms were synthesized in multistep synthetic routes. A Buchwald–Hartwig amination of brominated precursors, thermolysis of azide precursors, and a Cadogan reaction of nitro-substituted precursors were successfully applied to eventually build-up pyrrole rings to stable and soluble fused

• replacement of sulfur by nitrogen atoms in the tetra- and hexacyclic systems leads to a red-shift in absorption, a decrease in oxidation potential and energy gap. On the other hand, the replacement of a thiophene ring by benzene leads to the opposite effects. Keywords: Buchwald–Hartwig amination; Cadogan

• -heteroacenes, dimeric thieno[3,2-b]pyrrole [8] and trimeric dithieno[3,2-b:2’,3’-d]pyrrole (DTP) [9], are long known but still frequently used as building block for organic electronic materials [10]. By application of Pd-catalyzed Buchwald–Hartwig amination/cyclization reactions of brominated thiophene-based

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• bromide in 1-bromo-4-chlorobutane (16) with sodium azide to give azide 17 in 52% yield (Scheme 5). Treatment of 17 with potassium phthalimide and catalytic potassium iodide was followed by hydrazine unmasking to give the desired aminoazide 18 in 37% over the two steps. Reductive amination of 18 with dial

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• ferrocene–sumanene conjugates by employing reductive amination reaction for the formation of compounds 110 and 116. Whereas compounds 111, 113, and 117 were prepared by means of condensation reaction as depicted in Scheme 27. On the other hand, Lentz’s group has reported the synthesis of sumanenylferrocene

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• amination of the tetrahydropyranone 50 to generate the (all-cis)-tetrahydropyran fragment. This group reported multiple different routes to 50. In an abortive route, the addition of allyl-Grignard to 5-methylfurfural, followed by the resolution of the racemic homoallylic alcohol with Amano lipase gave

• -methyl-3-buten-1-yl tosylate in the presence of Grubbs’ 2nd generation catalyst yielded 59, which, upon elimination with potassium tert-butoxide led to the diene 50. The reductive amination of 50 afforded an inseparable mixture of the C-14 amines (6:1 ratio). However, the amidation of this mixture with

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• lead to acceptable results. Therefore, we decided to modify the reaction scheme. After alkylation, compound 2 was instead brominated, followed by amination of 4 leading to the desired diamino product 5a. Amine protection and subsequent coupling procedures, leading to 8, were the same as described in

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• . Thus, an efficient method for the synthesis of carbazoles via an intramolecular C–H amination was developed, using N-substituted 2-aminobiaryl derivatives as the substrates (Figure 11) [76]. This procedure was carried out at 80 °C and led to the formation of various interesting coupling products with

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• ] for a decarboxylative amination of indoline-2-carboxylic acids with azodicarboxylate esters. Another photocatalytic strategy for accessing C(sp3) radicals from carboxylic acids proceeds through a reductive decarboxylation pathway. This approach relies on the conversion of the acid into an easy

• -Acr+ scaffold. In 2015, they developed a site-selective C–H amination of arenes (Scheme 25) [110]. The arenes 25.1 could be aminated by various N-heterocycles 25.2 for the synthesis of the C–H functionalization products 25.3 with fine-tuned Mes-di(t-Bu)Acr+ (OD4) as a photocatalyst. In this

• generation, the use of hydroxylamine derivatives has turned out to be very efficient [128][139]. The generation of amidyl radicals using organophotoredox catalysis was first reported by Pandey and Laha in 2015 (Scheme 30) [146]. They developed an intermolecular cross-dehydrogenative benzylic C(sp3) amination

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• catalytic amination of (E)-cinnamic acid The enzyme phenylalanine aminomutase (PAM) from Taxus chinensis catalyzes the stereoselective isomerization of α-phenylalanine to β-phenyalanine 111a–c. Mechanistic studies showed that (E)-cinnamic acid is an intermediate in this transformation [63]. Accordingly

• hand, Wade et al. reported that ester 138b (R = iPr) afforded the isopropyl 3-fluorophenylalaninate (139b) as racemate in 45–50% yield [70] under similar reaction conditions (Scheme 31). 2.6. Fluorination and reductive amination of phenylpyruvate A direct fluorination of the ester derivatives of

• phenylpyruvic acids 140a,b with F2 followed by hydrolysis of the resulting fluoropyruvates in 50% isopropanol in the presence of NaHCO3 gave 3-fluoro-3-phenylpyruvate 141 in 40–50% yields [68]. The direct reductive amination gave a partially racemized mixture of threo and erythro-136 with the erythro

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• bases, such as K2CO3, Na2CO3, NaHCO3, etc. Another approach for the synthesis of compound 17 is the amination of compound 15 to give compound 16. Subsequently, compound 17 was obtained by hydrolysis of compound 16 using TFA in DCM. The synthesis of compounds 15–17 was described in a similar manner in

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• acrylate aldehyde 9 in 61% yield. The next step involved the crucial reductive amination reaction between aldehyde 9 with indolamine 10, which had been obtained via Fischer indole synthesis – the reaction of phenylhydrazine with 5-chloro-2-pentanone [35]. Initial reduction attempts using sodium

• final two steps, the reductive amination reaction and the hydroxamic acid preparation. Using the same reaction conditions developed for TOI1, we proceeded with precursors 22 and 23, which were obtained in 61% and 68% yield, respectively. The desired hydroxamic acid TOI2 and TOI3-rev were obtained in 49

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• amination of NHP esters. Photocatalytic decarboxylative alkynylation using [Cu(I)(dq)(binap)]BF4. Copper-photocatalyzed alkylation of glycine esters. Copper-photocatalyzed borylation of organic halides. aUnder continuous flow conditions. Copper-photocatalyzed α-functionalization of alcohols with glycine

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