Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• lactams. Notably, all reported structures have alkyl or aryl substituents in position 3 of the clavam ring. Conversely, clavams substituted with alkyl chains at the 2-position, to the best of our knowledge, have not been previously reported and are absent from common organic compound databases. To explore

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• Table 4. The Newman projections of the halogenated analogues show deviations from parallel alignment for the C2–F and C4–X substituents of 12.08° for 17, 17.08° for 13, 18.18° for 14, and 18.59° for 15 (talopyranose, 18: 5.92°). This deviation is responsible for the distance between F2 and the halogen

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• were usually obtained when the substituents at the double bond differed significantly. When the substituent hindrance was less pronounced, the ratio was less significant (2f, 2j). Interestingly, a reverse regioselectivity was observed depending on the starting alkenes. For the terminal alkenes, the

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• , University of Hyogo, 3-2-1 Koto, Kamigori-cho, Ako-gun, Hyogo 678-1297, Japan 10.3762/bjoc.20.206 Abstract We describe herein a facile method to access 2,3-epoxyesters with fluorine-containing substituents at their 3-position starting from the corresponding enoates by utilization of the low-costed and easy

• ) Grignard-based cuprates. These processes usually yielded the addition products along with the epoxy ring opening at the 2 position via the SN2 mechanism, affording 3-Rf-3-hydroxyesters with the incorporation of a variety of substituents at the 2-position in a highly anti-selective fashion. We believe that

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• that six-membered core structures are also weaker XB donors (iodininium 3OTf) than iodolium 1OTf [13]. Furthermore, the importance of substituents in the core and on the outer rings was demonstrated (XB donors 2OTf and 4OTf). Nachtsheim reported the synthesis of N-heterocyclic substituted monocationic

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• established for these compounds. The electrochemical behavior of the studied compounds is influenced by several factors: the nature of the heterocycle and its substituents, the presence of a sulfur atom in the catechol ring, or a thione group in the heterocyclic core. The radical scavenging activity and

• neuroprotective, antihypoxic effects, act as antiparkinsonian agents [3][4][5], exhibit antitumor and antibacterial activity [6][7][8], possess antioxidant properties for regulating free radical processes [9][10][11]. The functionalization of polyphenolic compounds by introducing various substituents or

• average lengths of the С–С bonds of six-membered carbon cycle С(1–6) (1.396 ± 0.013 Å in 5, 1.397 ± 0.009 Å in 6, 1.396 ± 0.012 Å in 8) are typical for catechols [50][55][56]. The presence of complex polyfunctional substituents affects their spatial location regarding a catechol fragment. In most cases

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• slightly more efficient with electron-poor substrates. On the other hand, high enantioselectivity was maintained over the aldehyde scope regardless of steric size and position of the substituents. A few years later, Wulff and co-workers [42] further elaborated the aza-Cope rearrangement methodology by

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• derivatives bearing both aromatic and aliphatic substituents. The NO-donor ability of the synthesized furoxano[3,4-d][1,2,3]triazin-7(6H)-ones was additionally evaluated. The elaborated method provides access to novel nitrogen heterocyclic compounds with potential applications as drug candidates or

• ][1,2,3]triazin-7(6H)-one 2-oxides 1 (Scheme 2). Note, that triazinones 1a–d bearing aryl substituents at position 6 were obtained in high yields, however, in the case of the 2-methoxyphenyl derivative the yield of target triazinone 1e was somewhat lower arguably due to steric hindrance. To our delight

• , furoxancarboxamides 2f–h bearing aliphatic substituents or amino acid residues also smoothly underwent the studied tandem protocol and the corresponding biheterocyclic compounds 1f–h were obtained in yields of 45–77%. After having developed a general method for the synthesis of target furoxanotriazinones 1a–h, we

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• -trifluoromethylsulfonyl)aziridine 6c was furnished in 47% yield. Similarly, 2,6-difluorosulfonyl-substituted iminoiodinane 2d afforded aziridine 6d in 52% yield. The aziridination procedure was tolerant of heterocyclic substituents on the iminoiodinane, N-(5-methylpyridin-2-ylsulfonyl)aziridine 6e could be obtained in 46

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• by observing the influence of substituents on a reaction outcome. However, Hammett parameters have shown to not fully describe observed trends. Therefore, complementary representations capturing other properties of a molecule have been derived (vide infra) [28]. While traditional linear free energy

• Hammett parameters account only for the electronic effect of substituents, much research has been devoted to develop physical-organic descriptors, which consider steric effects and separate the electronic effect into contributions from resonance and induction, among others [27][77][78][79][80][81]. In

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• aromatic hydrocarbon radicals, which can persist in air-saturated solutions for several days to months, have been synthesized by employing bulky substituents around the spin-localized carbon center [13][14][15]. These stable radicals have paved the way to elucidate the nature of radical species, advancing

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• the field of bioconjugation and materials research. We previously reported a regioselective double addition of organic azides to octadehydrodibenzo[12]annulene derivatives with electron-rich alkyloxy substituents. In order to increase the reaction rate, electron-withdrawing substituents were

• ], and crosslinked polymers [14][15][16][17]. Since crosslinking polymers requires high reaction efficiency under mild conditions, developing such reactions is crucial. We previously reported the regioselective double azide addition to octadehydrodibenzo[12]annulene with hexyloxy substituents (DBA-OHex

• ), which are readily accessible by the oxidative acetylenic coupling of a 1,2-diethynylbenzene derivative (Figure 1) [18]. The chemical stability of DBAs depends on the electronic character of the substituents. Electron-donating alkyloxy groups are known to enhance the stability of DBAs. On the other hand

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• well as electron-withdrawing substituents on the two phenyl rings in compounds 1, such as methyl, methoxy, halogen atoms (F, Cl, Br, I), CF3 and SO2CH3, were well tolerated, and their electronic effects insignificantly impacted the formation of 3. Similarly, N-benzyl-3-oxo-3-phenylpropanamide (3w

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• was released [57] allowing direct comparison of different substituents. On the basis of the calculated Hammett constants, we have selected a model series of 1,3-diketones, bearing heterocyclic substituents with a range of electron-withdrawing ability (Figure 2). For the amine model series, we used

• 0.267/0.305) substituents reacted with primary and secondary alkylamines, requiring prolonged heating and a 1.5 excess of amine (Scheme 4), to give meta-substituted arylamines in reasonable synthetic yields. In the case of 1,3-diketone 1d, the addition of molecular sieves is necessary in order to reduce

• the formation of the enamine side-product. Similar to 1,3-diketone 1b, an extremely low conversion of 1c and 1d was observed in the reaction with aniline. The isoxazol-3-yl or furan-2-yl substituents have calculated Hammett constants below 0.200 (Figure 2), thus based on the above observations, a slow

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• [131][132][133], it is quite likely that alternariol and its derivatives are partly present in the organisms as O-glucosides, acetates, or sulfates [134][135], where these substituents are most generally cleaved during the isolation and work-up processes. These derivatives (glucosides and sulfates) are

• further data did no become accessible to the author. The given name ‘5-hydroxyaltenuene’ is misleading and its utilization is not recommended [269]. Substituted altenuene and diastereomers: A number of altenuene diastereomers with further O-substituents are given in Figure 16. 2-O- and 3-O-acetylaltenuene

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• nitrogen-containing compounds [3][4][5][6][7]. Furthermore, by adjusting the substituents on the nitrogen, reactivity can be controlled and solubility in various solvents can be tuned (Figure 2). However, the use of isocyanide as a C1 resource is somewhat limited compared to that of carbon monoxide [8

• yields. In the case of tert-butyl and benzyl isocyanides, the substituents on the nitrogen of imidoyl radical 2 (R = t-Bu or PhCH2, E = Et2P or Ph2P) were eliminated to give cyanophosphines (R’2P–CN, Scheme 7) [38]. On the other hand, we attempted a photoinduced addition of phosphorus–phosphorus

• substituents on the heteroatom. For this reason, the 1,1-addition is less likely to proceed as with group 16 or 15 heteroatom radicals. In the case of stannyl and silyl radicals, the alkyl group of the isocyanide is eliminated as an alkyl radical from the imidoyl radical intermediate 2 [42]. The formed alkyl

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• % using hex-5-enenitrile. Conclusion In summary, fine-tuning of the experimental conditions gave us access to original ortho-cyanoalkylated aryl perfluoroalkylsulfur derivatives. We have also shown that structural diversity is possible by varying the substituents on the aromatic ring, the perfluoroalkyl

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• formate (Scheme 8) [58]. Upon reaction with β-ketoesters, hydrazone 30 is formed, which reacts via intramolecular Knoevenagel condensation to give the corresponding pyrazoles 27. The method tolerates β-ketoesters with alkyl substituents and various ketoamides. In addition, an example could be synthesized

• and elimination to give the corresponding pyrazoles 52 (Scheme 15) [70]. The cross-coupling introduced various aryl substituents at position 4. Furthermore, using 1,4-diiodobenzene as a starting material allows access to bispyrazole derivatives. According to Beller [71], using bisadamantyl-type

• to synthesize 3,4-substituted pyrazoles 57 from iodochromones 55, arylboronic acids 56, and hydrazines (Scheme 16) [72]. During the Suzuki step, electronically and sterically diverse substituents were successfully coupled to chromones. Notably, a single regioisomer is formed when methylhydrazine is

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• methodology (Table 2). At first, various arylidenemalonates 2 were tested with a phenyl analog of curcumin 1. The reaction of 1a with arylidene malonates 2a–c, bearing weakly electron-withdrawing para-substituents, produced the corresponding double Michael adducts 3a–c, respectively, in good to high yields

• curcumins 1 with arylidenemalonate 2 can be explained in terms of the relative stereochemistry of the substituents in the enolate arising from the first Michael addition (Figure 3). Comparison of the two possible transition states TSI and TSII for second Michael addition suggests that a severe 1,3-allylic

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• regardless of the electronic properties of the substituents on the N-phenyl ring. When dissymmetric diaryl ketone-derived substrates were employed, the C–N bond formation occurred selectively on the most electron rich aromatic ring. According to the proposed mechanism, this dehydrogenative cyclization of

• substituents on the aromatic moiety regardless of their electronic properties. However, 4,5-disubstituted 1,2,3-thiadiazoles could not be accessed with this methodology. Mechanistically, control experiments with radical trapping agent such as TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) or 1,1

• ,N-disubstituted hydazones 101 for synthesiszing tetrazoles 103. Sodium azide could be an alternative source of azide, albeit with both slightly lower yields and Faradic efficiency. Remarkably, (hetero)aromatic as well as aliphatic aldehydes proved to be efficient. Various substituents on the N(sp3

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• oxymethine H15, which in turn was correlated with a methylene H214. The pyrrole moiety with the same substituents as 1 was deduced from HMBC correlations. Therefore, compound 2 was determined to have a non-branched alkyl chain with a hydroxy group at C15. Meanwhile, 3 possessed a terminal ethyl group, which

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• photochemical sequential transformation. With the optimal flow reaction conditions in hand, we next investigated the scope of substrates 1 by introducing a series of substituents to the terminal phenyl group. The results of the batch reaction system are also shown for comparison in Table 2 (right-hand side) [55

• reactions of aldehydes with a series of substituents introduced to the terminal phenyl group were further investigated (Table 3, entries 4–7). Aldehydes having an electron-donating methyl group and an electron-withdrawing bromo group at the para-position of the phenyl moiety gave products 3o and 3p

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• analysis, which revealed that two alkyl substituents were located on the same side of the molecule (Figure 2a). Compared to the planar structure of 1 (Figure 2b) [2], 2a displays a nonplanar structure due to the sp3 carbon atoms adjacent to the nitrogen atoms. The 1H NMR spectrum of 2a confirmed that the

• . Finally, another isobutyronitrile radical reacts with I at the convex face to form the major product 2a, with two alkyl substituents on the same side of the molecule. The mean-plane deviation (MPD) of I was 0.293 Å, where the mean plane was defined by carbon, nitrogen, and nickel atoms of the norcorrole

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• simple and mild method to selectively generate N1- or N2-substituted indazole analogs when the substituents appear to favor one over the other. Ideally, it would be greatly beneficial if the desired high regioselectivity on N1 or N2 could be achieved when commercially available chemicals, such as

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• spectra are very similar. These results indicate that substituents with different functional groups can be attached to DPP 2 without significant modification of their optical properties. The observed Stokes shifts for dyes 3 and 4 averaged in the range of 60–70 nm. All compounds exhibited high