Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• shifted relative to the one of the Z-isomer. Depending on the substitution pattern, the thermal lifetimes of metastable E-isomers at 25 °C vary from hours to days and sometimes even years [12][13][14]. Remarkably, for sterically hindered hemi-indigo derivatives, thermal lifetimes of the metastable states

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• cyclopentanone and ammonia. The polycyclic amine product was then converted into a sterically shielded polycyclic nitroxide. Sterically hindered nitroxides have high chemical stability [5] and can be used as spin labels to study biopolymers in cells [6]. The introduction of spirocyclic moieties has a smaller

• effect on the reduction rates of nitroxides than does the introduction of linear alkyl substituents. However, spirocyclic nitroxides may have much longer spin relaxation times at 70–150 K which make them attractive agents for spin labeling [7][8][9]. Sterically hindered nitroxides can be used as spin

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• para-substituted aryl bromides, high regioselectivities in favor of the α-arylations were observed. The meta-substituted 3-bromoacetophenone and methyl 3-bromobenzoate also afforded the α-arylated lilolidines 10 and 11 with high regioselectivities. Conversely, with the more sterically hindered aryl

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• 7c. 1,3-Dipolar cycloaddition of nitrones to alkenes is known to be reversible [13][14]. We recently reported a similar reversibility of the intramolecular cyclization of sterically hindered pent-4-enylnitrone of the 2H-imidazole series [15]. Treatment with Zn in an AcOH/EtOH/EDTA/Na2 mixture was

• in the side chain, the hydroxymethyl group in 9a–c was protected via acylation. Heating of 9a–c with an excess of acetic anhydride in chloroform quantitatively afforded the corresponding esters 10a–c. The products of acylation of the sterically hindered amino group were not detected in the reaction

• general synthetic approach to sterically hindered spirocyclic nitroxides based on an intramolecular 1,3-dipolar cycloaddition reaction in alkenylnitrones followed by isoxazolidine ring opening. The resulting asymmetric pyrrolidine nitroxides have unexpectedly high rates of reduction with ascorbate. These

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• 4-phenyl-2-butanol into benzylacetone in only 30 min (Scheme 6, ketone 11b). This protocol was successfully extended to other secondary alcohols to afford the corresponding ketones 11b–19b in high conversions and yields. The oxidation of sterically hindered secondary alcohols such as adamantan-2-ol

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

• this methodology resulted in homocoupling of bromoalkynes. Among the examined Cu(I) and Cu(II) salts, Cu(OTf)2 was proven to be the optimal one. Both EW and EDGs were well tolerated except 2-amino-6-methylpyridine which might be sterically hindered due to methyl group at 6-position. The use of

• EDGs at p- and m-positions gave a higher yield than sterically hindered o-substituents and EWGs. Moreover, the absence of metal leaching as tested by atomic absorption spectroscopy (AAS) demonstrated the heterogeneous nature of the used catalyst. Recently, a robust, ligand and additive-free

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• loading was 0.61 mmol/g. Lower loading of the resin was used in order to enable quantitative incorporation of the sterically hindered, glycosylated building blocks. The synthesis of tri- and pentapeptides (Scheme 1B) was performed manually on solid phase [28]. The obtained glycopeptides were cleaved from

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• [4][5]. Stability and radiochemical improvements were investigated by Matesic et al. [5]. For instance, electron-donating 18F-arylsulfonyl fluoride 1 was >98% stable in the buffer at 3 h, while the electron-withdrawing compound 2 was only 8% stable [5] (Figure 1). The more sterically hindered 18F

• [6]. To further investigate the stability of 18F-sulfonyl fluorides, the sterically hindered compound 4 was selected with enough steric bulk in the 2,6-position. The initial chlorosulfonylation reaction was performed using 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) as a source

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• . The configuration of C-5 in each stereoisomer was established using NOESY experiments and theoretical models. The main limitation of this approach was the impossibility to incorporate both aromatic and sterically hindered amines (e.g., tert-butylamine). Besides the reports of Rivera’s and Ramírez’s

Extending mechanochemical porphyrin synthesis to bulkier aromatics: tetramesitylporphyrin

• Qiwen Su and
• Tamara D. Hamilton

Beilstein J. Org. Chem. 2019, 15, 1149–1153, doi:10.3762/bjoc.15.111

• , simple, room-temperature method for producing tetra-meso-substituted porphyrins with bulky substituents. Keywords: condensation; grinding; mechanochemistry; milling; porphyrin; sterically-hindered; Introduction Porphyrins and related macrocycles such as chlorins, corroles, and bacteriochlorins carry

• could accommodate a sterically-hindered aldehyde, and produce TMP at room temperature and in the absence of added solvent for the condensation step, using relatively simple reaction conditions. The use of mechanochemistry to bring about a no-solvent-added acid-catalyzed condensation between aldehydes

• to cyclocondensation of pyrrole with a sterically-hindered aldehyde. After oxidation to give a porphyrin with bulky substituents, isolated yields are comparable to those obtained from high-temperature syntheses (though still lower than the 30% obtainable with added solvent at room temperature). The

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• elimination to form N,N-dialkylaminomethylstyrenes 4 in yields higher than 60% (Table 1). Our attempts to synthesise highly sterically hindered 2-vinyl-N,N-diisopropylbenzylamine by an analogous method failed at the stage of the quaternary salt 3. The application of terminal dihalogen derivatives afforded

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• intermediate F, in which the C2′-acyl group participates in delocalization of the carbocation on the C1′ position. Nam approaches and attacks this carbocation from the less sterically hindered face to give the β-nicotinamide riboside derivatives (Figure 3). A very comprehensive and thorough discussion of the

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• was not obtained by treatment of the corresponding cyclopropenylcarbinol substituted by an n-undecyl group with trichloroacetonitrile, even under forcing conditions. The authors tentatively suggested this may be due to the sterically hindered n-undecyl chain although this issue was not fully

• produced in excellent yield (94%). More sterically hindered substituents were tolerated at C3, as illustrated with the isolation of the spirocyclic compounds 58j (60%) and 58k (77%), and alkylidenecyclopropane 58l possessing a fully substituted three-membered ring was also formed in excellent yield (96

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• reactions a 1:3 ratio of A/B was applied. Practical limitations are that A and B have to be of significantly different polarity for easy column chromatographic separation and that sterically hindered olefins are not tolerated. For some alkenes, e.g., styrenes, the homodimerization is too fast leading to

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• almost no preferential selectivity for AB, AC or AD regioisomers. Breslow et al. [17] used the 1,3-dimethoxy-4,6-benzenedisulfonyl chloride as a capping agent to prepare the AB regioisomer. Subsequently, Fujita et al. [18] selectively capped the primary rim of α-CD using a special, sterically hindered

• prepared the target 6A,6X-heterobifunctionalized α-CDs. Mesitylenesulfonyl was chosen as the appropriate functional group for insertion in the α-CD skeleton because it is sufficiently stable for reverse column chromatography and more sterically hindered than a tosyl group. The idea of attaching the

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• perspective, a few closely related glycosylations are shown in Scheme 4. Firstly, our own glycosylations using the 4-O-Bz variants, gave a lower yield, when using the TBDPS–TBDPS variant, of 36% [44]. The less sterically hindered Bn–TBDPS variant gave yields of 47%, which are comparable to the 3,4-diol

• be synthesized in 4 less steps than otherwise required. These results show, how the desired protecting group pattern can direct which glycosylation strategy to choose: In the less sterically hindered cases, a 4-O-protecting group, such as the benzoyl or benzyl, can be preferable. However, when a

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

• the sulfur atom. Bis(trifluoro)acetate 16 resulted from the opening of the ring is hydrolysed by TBAH to yield diol 17. Conversely, sterically hindered double bonds of 14 are not easily accessible to the sulfonium ion; therefore, the Pummerer intermediate α-thio carbenium ion 18 is generated through

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

• electron-rich triazolochromenes 5b and 5c, resulting in a drastic loss in yield for the more sterically hindered compound 5c. Furthermore, electron-deficient and halogenated analogs 5d–f were successfully synthesized. In a next series, we examined the substitution pattern on the nitroalkene part. Electron

• (E)-1-nitro-4-(2-nitrovinyl)benzene and sterically hindered 2-hydroxy-1-naphthaldehyde, only the oxidized product analogous to 6 was observed. 2-Hydroxy-4-nitrobenzaldehyde and 2,6-dihydroxybenzaldehyde were unreactive in the cycloaddition reaction. As previously mentioned, solid salicylaldehydes

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• corresponding conjugated carboxylic acid 4j in 75% yield. The alkenyl triflate 3k prepared from the corresponding aldehyde was also carboxylated, and its corresponding product 4k was obtained in moderate yield. The catalyst CoI2(Me2phen) was also effective with sterically hindered aryl triflates: the

• tolerated in the reaction. Sterically hindered substrates could be subjected to the reaction, and 26g was obtained from 25g. Moreover, a substrate having a heteroaromatic ring (25i) was converted into its corresponding carboxylic acid 26i. Alkenylboronic esters 27 were also converted into the corresponding

• ) in good-to-high yields. Notably, sterically hindered substrates (34d and 34f) were allowed by elevating the reaction temperature. A plausible reaction mechanism is shown in Scheme 32. First, a phenoxide 34’ generated by the reaction of 2-arylphenol with t-BuOK reacts with a Rh complex A to generate a

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• ] adduct 19. Traces of unidentified oligomers and functionalized [2 + 2] macrocycle were also observed in the reaction mixture. It can be argued that, due to steric hindrance, the alkylation of macrocycle 6 is slow. The less sterically hindered cyclic trimer 7 and the linear oligomers are therefore faster

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• azobenzene strongly influences the life time of each redox-switching state. In the (E)-form, the wheel can easily move between the TTF and dihydroxynaphthalene station. In the Z-form, this movement is sterically hindered and slowed down. The wheel cannot shuttle to its energetically preferred station. This

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives

• Jiao-Na Han,
• Cong Du,
• Xinju Zhu,
• Zheng-Long Wang,
• Yue Zhu,
• Zhao-Yang Chu,
• Jun-Long Niu and
• Mao-Ping Song

Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183

• amino group at C5 of the substrate 1g was also compatible with the transformation (33%). When a methoxy group was located at the C7 site of the naphthylamine, sterically hindered product 3ha was obtained in 81%. Besides, some benzylamine derivatives (N-(1-phenylethyl)picolinamide and N

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

• . Aliphatic aldehydes gave poor yields, with sterically hindered examples not reacting at all. The author attributed this to the formation of enamines. Under the reported reaction conditions primary aliphatic and aromatic amines all produced imines. The benzamide moiety is somewhat common in biologically

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• yields and moderate to excellent enantioselectivities. Recently, an intermolecular asymmetric dioxygenation reaction has been disclosed by Muñiz and co-workers (Scheme 5) [52]. They found that the chiral iodoarene catalyst 13, bearing sterically hindered N-arylamido substituents, was essential for the

• attack of acetates to the exposed re-face establishes the S-configured benzylic C–O bond. Without the hydrogen bonding effect, the same reaction with a diester-containing iodoarene catalyst was explored [55]. The sterically hindered adamantyl-substituted catalysts 17 were demonstrated to be efficient to

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• pathway A or B as depicted in Scheme 2. Especially when the sugar alcohol is not sterically hindered, phosphorus transfer occurs to yield a phosphine-activated anomeric alcohol (a glycosyloxyphosphonium ion, pathway A). This in turn can be attacked by the deprotonated nucleophile resulting in an

• . [26]. Assuming that the alcohol is sterically hindered and thus represents a relatively weak nucleophile, the deprotonated acidic partner, NuO−, can react with the phosphonium intermediate first to afford an intermediate Nu-O-PR’3. In the case where a carboxylic acid is used, Nu-O-PR’3 represents an

• et al. using a modified Appel-type procedure [121]. A striking oxidation reaction of alcohols to carbonyl compounds was disclosed by Mitsunobu and colleagues, involving the sterically hindered nitrophenol 130 [122]. With sugars like 129, the Mitsunobu glycosylation is hampered, and instead an