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

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• of aryl iodide. The latter is then used for a sequential ruthenium-catalyzed ortho-C–H functionalization directed by the pyrazole group (Scheme 37) [76]. Starting from non-symmetrical diaryl-λ3-iodanes, the electron-poorest or more sterically hindered aromatic group is first transferred to the 3,5

Steric “attraction”: not by dispersion alone

• Ganna Gryn’ova and
• Clémence Corminboeuf

Beilstein J. Org. Chem. 2018, 14, 1482–1490, doi:10.3762/bjoc.14.125

• Ganna Gryn'ova Clemence Corminboeuf Institut des Sciences et Ingénierie Chimiques, École polytechnique fédérale de Lausanne, CH-1015 Lausanne, Switzerland 10.3762/bjoc.14.125 Abstract Non-covalent interactions between neutral, sterically hindered organic molecules generally involve a strong

• lengths [73]. Conclusion The significance of stabilizing dispersion and electrostatic effects within sterically hindered hydrocarbons is well recognized. In such systems, electrostatic contributions are generally dominated by charge penetration, which increases with system size (bulk) and shorter

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• which the cobalt center is connected to a less sterically hindered terminal allene carbon [23]. On the basis of these results, a plausible catalytic cycle for the cobalt/chromium-catalyzed three-component coupling reaction is shown in Scheme 12. The three-component coupling starts with the oxidative

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• in the presence of NaH or n-BuLi (Figure 5) [46]. Conformational analysis of calixarene-diphosphite ligands revealed that presence of sterically hindered groups led to the formation of the predominantly cone-conformer. In order to check whether calix[4]arene-diphosphite ligands may also serve as

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• design of the cryptand by replacing the central benzene ring with a triazine unit (in which the H atoms of the ortho positions are replaced by lone electron pairs belonging to the N atoms). The resulting less sterically hindered cryptand 2 (Figure 1) was then tested for its ability to form host–guest

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

•  20. In 2016, Zhang and Yang reported an asymmetric palladium-catalyzed addition of arylboronic acids 60 to sterically hindered N-tert-butylsulfonylisatin imines 61 [80]. Among a variety of chiral ligands investigated, including different pyridine-oxazolines, oxazolines and (R)-BINAP, the chiral

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• plausible mechanism and transition-state model 27 for the formation of the major isomer through the attack of the carboxylic acid group to the ipso position of the naphthol ring from the less sterically hindered Re-face of the substrate 25. It is worth mentioning that very recently they have introduced a

• postulated the formation of possible intermediate 97 which favored the nucleophilic attack of the aryl ring from the less sterically hindered side. Later, Du et al. used this same precatalyst 12 to obtain spirofurooxindole derivatives with high enantioselectivity through cascade cross-coupling sequences [71

• , nucleophilic fluorinating technique of β-keto esters 102 using 106/HF/m-CPBA as a catalytic system to access fluorinated β-keto esters 103 with moderate enantioselectivity [73]. β-Keto esters having sterically hindered adamantyl or menthyl groups lead to good selectivity. However, no further enhancement of ee

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• obtain various dipeptides from standard amino acids as well as sterically hindered amino acids. Moreover, a pentapeptide Leu-enkephalin is successfully synthesized in its protected form using this coupling system. Similar to iodosodilactone, FPID can be easily regenerated after the reaction. The

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• avoided simply by using the reverse addition to give the desired product 13 in good yield. The choice of the order of addition is also of importance for substrates with more sterical hindrance. Here the trend is clear: it is advantageous to use the less sterically hindered TMS enol ether to generate the

• enolonium species 4 followed by the addition of the more sterically hindered TMS enol ether 5. For example, the addition of enolonium species 4 (R1 = Ph, R2 = Me) to the TMS enol ether 5 (R3 = Ph, R4 = H) led to formation of the product 14 in 30% yield with significant formation of 1-tosyloxypropiophenone

• as the major byproduct. However, when the order of addition was reversed, i.e., the enolonium species 4 (R1 = Ph, R2 = H) was cross-coupled with TMS enol ether 5 (R3 = Ph, R4 = Me) the same product 14 was obtained in 74% yield. Apparently, in these cases the sterically hindered nature of the