Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• -aminoethylphosphinate 123. Oxidation with sodium periodate and neutralization with adamantan-1-amine (124), afforded the adamantan-1-ammonium benzyl phosphonate 125. After treated with hydrochloride and coupled with benzyl ᴅ-lactate ((R)-26b) with BOP as activating reagent, the ammonium compound 125 was transformed to

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• library of these versatile carbamate building blocks (3, ca. 1 mmol scale), we decided to apply a scavenger column to perform in-line purification. This was achieved as previously reported [22] based on a mixture of Amberlyst A21 (a tertiary amine, ca. 2 equiv) and Amberlyst A15 (a sulfonic acid, ca. 2

• products (10–20%) was observed in several cases indicating the competitive attack of the isocyanate by adventitious water followed by the reaction of the resulting amine with a second isocyanate molecule. Consistent with the expectations, substituted phenylacetic acids such as ibuprofen showed an increased

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• amount of the moderately acidic (S)-TRIP (pKa = 3–4 in DMSO [113][114]) in dichloromethane afforded the chiral α-(trifluoromethyl)aminoaryl derivatives 177 in an excellent yield and enantiomeric excess (Scheme 42). The authors proposed that hemiacetal 175 and amine 176 react under the reaction conditions

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• and the subsequent aerobic oxidation by an amine. Single-electron oxidants such as cerium ammonium nitrate or K2S2O8 were used for the regiospecific ring opening of the simple gem-difluorocyclopropanes 134 (Scheme 58). The brominative ring-opening reactions of compounds 134 gave good yields of the

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• (Table 1). We found that a combination of CuI with an amine buffer system [31][32][33][34][35][36][37] suites substrate 5 better than the previously used CuSO4∙5H2O and sodium ascorbate catalytic system [22]. Most probably, this is due to the solubility issues of the starting material 5 in aqueous

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• was prepared by the original direct method [36] (65%, Scheme 1c), as the mono-Boc amine B-Boc was less accessible. As the amide coordination to Au(III) in general is challenging, and not successful in our hands, as discussed below, we wanted to prepare the reduced amine products (5a,b, 6a,b) from

• conditions were obtained by adding AlCl3 to the reactions. Complete reduction of polyamides 1a,b and 2a,b yielded the open tetraamine products 5a,b and the target cyclams 6a,b with four secondary amine functions in moderate to high yields (29–88%, Scheme 2) within 1–2 days. Au(III) coordination studies Amide

• -coordinated complex. This was evidenced by changes in NMR shift values, Δδ15Ncoord = δ15Ncomplex – δ15Nligand, by coordination. The observed Δδ15Ncoord values were in the range of 16.3–32.0 ppm for both the primary and secondary amine nitrogens, indicating a characteristic deshielding effect upon the Au(III

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• library building block acid chloride 2. The libraries were prepared in a 3-step manner: 1) amide coupling; 2) deprotection of the 2-methoxypyridine through hydrolysis at elevated temperatures; and 3) the final SNAr or Ullman step to introduce the amine vector with variable yields and chromatographic

• protonation and activation of the pyridine towards SNAr with HOAt (Table 4). Exploration of the C-4 amine vector As we moved forwards in the program, we were eager to develop our understanding of SARs (structure–activity relationships) from the C-4 vector. Although we could have adopted the same methodology

• as described in Scheme 5 for this exploration, we decided to focus on developing a more convergent library process than Genentech’s 3-step sequence from 2 (Scheme 1), aiming at introducing the amine moiety at C-4 at the end of the process. We envisaged a rapid, 2-step one-pot library process (amide

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• copper-catalyzed azide–alkyne cycloaddition (Scheme 2). The reaction took place in degassed DMSO at 50 °C with CuSO4 pentahydrate, sodium ascorbate and tris(benzyltriazolylmethyl)amine (TBTA) as chelating species. HPLC-monitoring of the reaction showed a full conversion after three days and the crude

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• have provided new opportunities to develop synthetic strategies [21][22][23]. Structurally, it has an unsymmetrical bicyclic arrangement, incorporating a secondary amine and bearing a quaternary center. Since the pioneering Tursch’s work [24], a variety of approaches to obtain these alkaloids have been

• ]D24 +7.43 (c 0.350, MeOH); {lit. [α]D +7.5 (c 2.0, MeOH), [26]}. The (−)-adaline precursor (+)-23b was also accessed from 17 in 5 steps, in an overall yield of 7.3%. Inspired by Gössinger’s work, Murahashi et al. prepared a nitrone from a cyclic amine. However, the route was improved by the

• (−)-adaline (1) and (+)-euphococcinine (2). The cyclooctatetraene derived selenides 82 and (+)-92 are, at some point, similar to the one obtained by Renbaun in the (−)-adaline (1) synthesis. Renbaun generated the quaternary center by adding a chiral amine to the cyclooctatetraene system. On the other hand

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• , France 10.3762/bjoc.16.256 Abstract The SF5Cl radical addition on unsaturated compounds was performed using an air-stable amine–borane complex as the radical initiator. This method showed to be complementary to the classic Et3B-mediated SF5Cl addition on alkenes and alkynes. A total of seven alkene and

• three alkyne derivatives were tested in the reaction, with yields ranging from 3% to 85%. Keywords: amine-borane complex; pentafluorosulfanyl chloride; pentafluorosulfanyl substituent; radical addition; radical initiation; Introduction The pentafluorosulfanyl (SF5) substituent has been attracting its

• freshly prepared [37]. It is therefore of interest to address this challenge in order to widen the scope of this transformation. Compared to trialkylboranes, amine–borane complexes have shown to be more stable [38]. Indeed, they are usually air-stable, and their preparation from NaBH4, H2SO4 and amines

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• carbene complex intermediate and a mechanism was proposed (Scheme 10B). An nucleophilic attack of the amine nitrogen onto the alkyne 139 under the effect of activated Pt(II) A produces zwitterionic intermediate B. Elimination of the methoxy group from zwitterion B generates the α,β-unsaturated carbene

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• the nitro groups or (ii) concomitant reduction of the nitro groups and the allyl moieties. Thus, the reaction of 4a with SnCl2∙2H2O in ethanol gave the corresponding amine 5 in 57% yield after column chromatography on alumina. On the other hand, the four-day stirring of 4a with Pd/C under a H2

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• desired pyrroles 4c–e in moderate to good yield. Notably, methyl 2-methyl-1-phenyl-1H-pyrrole-3-carboxylate (4c) is a key intermediate in the synthesis of a TRPM8 antagonist [43]. The substrate scope of the aromatic amine component was then examined, and the remarkable efficiency of our pyrrole synthesis

• was reflected by the tolerance of a broad range of functional groups attached to the aromatic amine. For example, anilines bearing methyl (in 4f), phenyl (in 4g), and halo functionalities (in 4h–m) were readily compatible with the AlCl3 and 1,4-dioxane system. In these cases, the pyrrole products were

• synthesis, we also observed an unexpected reaction in which the pyrazolo[3,4-b]pyridine scaffold was constructed under analogous conditions. As shown in Scheme 6, In the presence of a catalytic amount of AlCl3 and 1.2 equiv of KI, 3-methyl-1-phenyl-1H-pyrazol-5-amine (1b) reacted smoothly with 2a and 3a

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• group in 12 attenuates the nucleophilicity of the molecule, rendering the attack on the relatively bulky phosphorylated nitronate 2 inefficient. To prove this, we decided to moderate the basicity of the amine function by protection with a sulfonyl group. Gratifyingly, the N-tosylamine 17 [48] reacted

• was concentrated in vacuum. The crude product was purified by flash column chromatography eluting with EtOAc/petroleum ether 1:6. Then, the amine was afforded via a Gabriel synthesis using a modified protocol described in the literature [52]. To a stirred solution of 6-bromo-2-(bromomethyl)quinoline

• hydrazide was filtered off and rinsed several times with cold ethanol. The combined filtrates were concentrated under reduced pressure to provide the crude amine, which was purified by flash column chromatography on silica gel, eluting with a mixture of dichloromethane/ethanol/triethylamine, gradient 80:10

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• is desired, in order to introduce two or even more functionalities in a specific manner. For example, in earlier work we have used amine-NHS coupling reactions in combination with CuAAC to prepare double labeled RNA molecules for FRET analysis [19]. The conjugation of, sometimes rather large

• not protected, side reactions were not observed and good yields (79%) of the C8-iodo derivative 3 were achieved. Prior to Sonogashira coupling of the linker moiety, the exocyclic amine of the nucleoside derivative was protected with an isobutyryl group, and the silyl groups at the sugar hydroxy

• without changing the reaction conditions used for the previous iodination of 2, resulting in the product 11 with a yield of 83%. The protection of the exocyclic amine lead to nucleoside intermediate 12, from which the 3′,5′-O-di-tert-butylsilyl group was selectively removed with HF-pyridine without

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• could not function as stimuli-responsive surfactants in our setup (see Supporting Information File 1 the for binding study with compound 16). This was somewhat surprising as the prepared amine-functionalized compounds 9, 10 and 11 resemble the compounds investigated by Yuasa and co-workers as stimuli

Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of ¹J_C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites

• Md. Rokon Ul Karim,
• Enjuro Harunari,
• Amit Raj Sharma,
• Naoya Oku,
• Kazuaki Akasaka,
• Daisuke Urabe,
• Mada Triandala Sibero and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 2719–2727, doi:10.3762/bjoc.16.222

• commercially available imidazole derivative, 4-isocyano-1H-imidazol-5-amine, with MeMgBr. On the other hand, 9 was synthesized in three steps from pyrimidin-2-amine. Imidation of the starting material with 1,1-dimethoxy-N,N-dimethylmethylamine gave an N,N- dimethylformimidamide derivative, which was cyclized

• production medium, which consists of 0.2% glucose, 2.5% soluble starch, 0.5% yeast extract, 0.5% polypeptone (Wako Pure Chemical Industries, Ltd.), 0.5% NZ-amine (Wako Pure Chemical Industries, Ltd.), 0.3% CaCO3, and 1% Diaion HP-20 (Mitsubishi Chemical Co.) in natural seawater (collected from Toyama Bay

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• assemblies of the peptides. The attachment of DEDDDLLI sequences to the ε-amine of the lysine residue of a tetrapeptide produces branched peptides that form micelles. Upon the proteolytic cleavage of the branch, catalyzed by proteinase K, the micelles turn into nanofibers. We also found that the acetylation

• assemblies of the peptides. The conjugation of Asp–Glu–Asp–Asp–Asp–Leu–Leu–Ile–Gly (DEDDDLLIG) sequences to the ε-amine of the lysine residue of a tetrapeptide Nap–ᴅ-Phe–ᴅ-Phe–ᴅ-Lys–ᴅ-Tyr (Nap-ffky) [9] produces the branched peptide 1, which forms micelles (Figure 1). When proteinase K catalyzed the

• allows the conjugation of the cleavable side chain, and tyrosine provides additional aromatic–aromatic interactions, as shown in a recent cryo-EM structure (PDB: 6X5I) [41]. Based on the above rationale, the DEDDDLLIG sequences attach to the ε-amine of the lysine residue of the tetrapeptide Nap-ffky to

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• weeks, while metalloligand 3 needs to be stored in an argon atmosphere at 3 °C and 1 even needs to be stored only in an argon atmosphere at −18 °C to prevent decomposition. The reduced stability of the amine precursors compared to cage 4 might be a result from the higher electron-donating capability of

• amine functions and thus a higher tendency to undergo one-electron oxidation reactions when stored under ambient conditions. In order to check the composition of heterobimetallic 4 we performed mass spectrometric experiments first. Figure 1 shows the ESI mass spectrum of metallosupramolecular cage 4

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• synthesized in the racemic and the enantiomerically pure form. The racemate rac-1 was obtained in four steps from triethylene glycol monomethyl ether by tosylation, substitution of the tosyl by an azide group, and reduction to obtain the corresponding amine (Scheme 1). This amine was coupled to racemic lipoic

• nanoparticle surface after immobilization. Compound 2 was prepared by starting from potassium phthalimide and 1,12-dibromododecane (Scheme 2). The product resulting from this step was treated with bis(2-pyridylmethyl)amine to give a DPA derivative that was coupled to (R)-lipoic acid after deprotection to

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• reproducibility of this method for large-scale synthesis (Scheme 3) and the removal of the sulfinyl auxiliary to give the free amine (Scheme 4). To our delight, 1.4 g of the desired product 3a was obtained when the amount of sulfinylimine 1 was raised to 1.0 g (5.0 mmol). Comparing with reaction of 0.3 mmol scale

• , only a slight decrease in the yield was observed (84%) along with the same stereochemical outcome. Also, the chiral sulfinyl auxiliary can be easily removed under acidic conditions to give the free amine. Treating 3i with HCl gas in methanol at 0 °C, the tert-butylsulfinyl group was cleaved under mild

• conditions and the target primary amine 4 was obtained with 57% yield. Conclusion In conclusion, we have explored arylethynes as new nucleophiles for the Mannich reactions of (R)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. Quite unexpectedly, the diastereoselectivity of the reactions were noticeably

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• with a typical π-stacking distance of 3.58 Å and a tilt angle of 5.8°. The free electron pair of the tertiary amine points towards the inside of the crown ether. In contrast, single crystals of NDIC8 (Figure 2c), obtained by slow evaporation of a concentrated dimethylformamide (DMF) solution, exhibit a

• from the secondary ammonium group of the axle to the tertiary amine in the crown ether wheel. An ITC titration with A1·PF6 gave a similar curve shape (see Figure S5b in Supporting Information File 1), though crown-7 ethers are too small to thread over the phenyl ring of A1·PF6 under the conditions of

• ). These results suggest that both ammonium axles form a similar type of equilibrium with NDIC7, where the protonation of the tertiary amine and the complexation in a nonthreaded complex might contribute. When using BArF24− as the counterion for A1, the binding energies increase by 6–8 kJ/mol, which

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• abundant amine groups. While groups are starting to investigate the usage of chitin and chitosan-based supports for heterogeneous catalysis, there are still scarce investigations on using these biomaterials on the nanoscale, which can allow for higher accessibility of their functionalities towards better

• and aldehyde–amine–alkyne (A3) coupling reactions [16]. Off this discovery, in this letter, we further expand the scope of using both ChNCs and ChsNCs as a catalyst support for Pd NPs to allow access towards other highly relevant C–C bond-forming reactions. A one-pot fabrication method is used to

• ChNCs and ChsNCs confirmed the structural and chemical functional properties of these nanomaterials. We turned to Fourier transform infrared (FTIR) spectroscopy to access the degree of deacetylation (DDA) of the prepared materials (Supporting Information File 1, Figure S2). The ratio of primary amine

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• level of theory, ωB97X-D/6-311++G(d,p) [16][18], resulting in conformer Iag (Figure 2). This conformer has one fluorine atom in an anti-orientation and the other one in a gauche-orientation relative to the vicinal oxygen atom (pointing towards the amine hydrogen atom). To evaluate the other possible

• geometry is quite similar among the three conformers. Only for Iga, where the gauche fluorine atom points to the opposite direction of the amine group, the triazole ring was farther away from the 1,2-disubstituted ethane moiety. Note that the gas-phase relative conformational energy ΔE increases, i.e

• Juaristi and Notario [9], and O’Hagan and co-workers [10]. Besides, there is also an interaction between the fluorine electron lone pair nF and the σ*NH orbital of the amine group (of 3.2 kcal mol−1, see Table 1). Iga also experiences this stabilizing hydrogen bond-like intramolecular interaction (nF → σNH

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• use of light would result in a greener reaction. where (a) is the definition of quantum yield and (b) is the quantum yield of a radical chain reaction. Review Enantioselective photocatalysis Amine catalysis Much of the history of amine catalysis used in photochemical reactions can be found in a review

• published by Zou and Bach [12], so the following are selected examples and recent developments of the field. Amine catalysis can be broadly split into enamine and iminium catalysis, both of which have been utilised in combination with photocatalysis. The first example of enamine catalysis in combination

• 1 with amine catalyst 3 to give enamine intermediate 4. The initiation step is proposed to be a reductive quench of the photocatalyst using 4 as a sacrificial reductant to give [Ru]•−, which can then reduce 2 to give electrophilic radical 2•. Addition of 2• to another molecule of 4 generates α-amino