Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• -tetraarylporphyrins 1 were synthesized from the corresponding 2-nitro-meso-tetraarylporphyrins in two steps by following the literature procedure [42]. The first step involved an amination of copper(II) 2-nitro-meso-tetraarylporphyrins by using 4-amino-4H-1,2,4-triazole in the presence of NaOH in refluxing ethanol

• /toluene 1:10 mixture under inert atmosphere to afford 2-amino-3-nitro-meso-tetraarylporphyrins which on reduction through sodium borohydride in the presence of 10% Pd/C in CH2Cl2/MeOH provided the desired porphyrins 1 in good yields as key starting materials for the synthesis of newly designed benzo[f

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• substituent was present (31 vs 70), and the highest yield was found with ortho-nitro ylide derivative 71. Computational studies, using abridged ylide 72 and thioacetamide as model substrates, were also performed to better understand the mechanism, specifically exploring the role of the nitro group and the

• reductive elimination of the iodoarene (Figure 16). They found 72 to possess secondary intramolecular halogen bonding between the nitro group and iodine’s proximal (stronger) σ-hole. The reaction initiated by selectively forming adduct 73 between the thioamide and the ylide, which possessed both halogen

• comparing ylides 31 and 70 in this reductive elimination step, which suggested that the ortho-nitro group of 72 (and 71, by extension) played a role other than lowering the activation energy of this step. Given that other optimized halogen- and hydrogen-bonded conformations were found between thioamide and

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• oxygen- or radical-sensitive functionalities (i.e., an amino (2w) or nitro group (2x)). On the other hand, oxidizable groups, such as alcohols (2e), and halogens, such as such as chloro and fluoro on the aromatic ring (2i ,2j, 2k), were well tolerated. However, the presence of a iodo group (2v

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• yields than with substrate 4d containing a strong electron-withdrawing group. The product 4n with the nitro group in the para-position of starting benzaldehyde 2n was formed in only trace amounts. A similar result was also observed in the case of isonicotinaldehyde (2m). These results were associated

• with an insufficient stabilization of the generated iminium cation due to the presence of a strong electron-withdrawing nitro group (for 3n), and due to the fact that the electron deficiency of the pyridine ring is strongly manifested in an acidic media (for 3m). In addition, the disadvantages of the

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• , Burkholderia thailandensis produces malleobactins (Figure 1), which possess nitro, nitroso, and azoxy groups [6]. Although the malleobactins are weaker iron chelators than related siderophores featuring hydroxamate groups [7], recent evidence suggests that their structural peculiarities might be of relevance

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• ). Furthermore, the desired products were not even obtained when the starting materials were connected to extra strong electron-withdrawing groups (such as a nitro group) on their aromatic rings. In addition, a series of cyclobutanone oxime derivatives were also smoothly transformed into the corresponding

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• -dicarbonyl compounds are treated with (diacetoxyiodo)benzene and tetrabutylammonium iodide, iodination occurs at the α-position of the nitro group, and the subsequent O-attack of the enol moiety leads to 2,3-dihydrofuran. Cyclopropane was successfully synthesized through C-attack as the acyl group became

• through an intramolecular aza-Wittig reaction, yielding cyclopropane-fused 2-quinolones [2]. A nitro group not only activates substrates and stabilizes the α-anion as an electron-withdrawing group but also acts as a nucleophile, electrophile, and leaving group, exhibiting diverse reactivities [3]. For

• compounds to give diarylated (oxoalkyl)malonates [6]. In the reaction using tin(II) chloride as the Lewis acid, the ring opening and nucleophilic attack of the nitro group occur, to produce functionalized isoxazolines (reaction d) [7]. In contrast, denitration under basic conditions generates highly

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• target products (Scheme 3, 5e and 5g). The drop was especially dramatic for the nitro group containing reagent 1f. Indeed, the transformation was accompanied by a number of side reactions according to TLC. To our delight, the protocol turned out to be suitable for α-sulfonyl-substituted alkyl acetates

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• nitrotoluene (22) under alkaline conditions (e.g., O2, KOt-Bu; O2, KOH, MeOH, ethylenediamine, etc.), as reported by Stansbury and Proops [33]. Aerobic oxidation of 22 in alkaline methanol with added ethylenediamine, gave 21 in 36% yield (Scheme 2), which is poor compared to that reported for the p-nitro

Synthesis, structure, and properties of switchable cross-conjugated 1,4-diaryl-1,3-butadiynes based on 1,8-bis(dimethylamino)naphthalene

• Semyon V. Tsybulin,
• Ekaterina A. Filatova,
• Alexander F. Pozharskii,
• Valery A. Ozeryanskii and
• Anna V. Gulevskaya

Beilstein J. Org. Chem. 2023, 19, 674–686, doi:10.3762/bjoc.19.49

• formally symmetrical structure of diynes 5, naphthalene rings A and B of molecules 5b and 5d differ in their structural parameters. At the same time, the monomer fragments of the nitro derivative 5e are identical. In the case of 5e, the naphthalene rings lie in parallel planes, while in crystals of 5b and

• DMAN fragments do not participate in nonvalent interactions and do not form short contacts. The recurring motif in the crystals is the coordination of the benzene meta proton by the nitrogen atom of the C≡N group. The structural parameters of both monomer fragments of nitro derivative 5e are identical

• nitro group. There are two types of independent non-equivalent dications, marked in blue and green, and two types of BF4− anions, marked in red and yellow, in the crystal structure of salt 11c (Figure S68 in Supporting Information File 1). Monomer fragments in both are identical (Table 2, Figure 5). The

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -methoxyphenyl (PMP)-protected imines 21 (Scheme 6A). By varying the reaction conditions, the syn-anti and the syn-syn diastereomers can be prepared with good yields and excellent stereoselectivity. Using nitroacrylate 23, the authors have also demonstrated a tandem conjugate addition/nitro-Mannich/lactamization

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• naphthylation of oxabenzonorbornadienes 30 with N-sulfonyl 2-aminobenzaldehydes 172 (Scheme 30) [76]. This reaction was amenable to a variety of EDG, EWG, as well as a broad scope of sulfonyl groups. Surprisingly, this reaction also proceeded smoothly with nitro substituents on the benzene ring which are

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• broad range of functional groups such as halogens, ester, aldehyde, cyano, and nitro (36c–g, 36–74% yield). It is noteworthy that a disubstituted compound 35j and a thiophene derivative 35k were also efficiently difluoromethylthiolated (36j and 36k, 72% and 65%, respectively). α-Substituted

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• reaction [33]. Thus, Knoevenagel condensation using the diaryl ether 29 and malonic acid gave the corresponding α,β-unsaturated compound 30, which was submitted to a concomitant hydrogenation of the double bond and the nitro group to give compound 31. Sequential diazotization/halogenation and

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• 4F in good yields (61 and 70%), whereas, in the case of 5-nitro-2-aminopyridine (G), the anticipated product 1G was obtained in low yield (34%). To check the synthetic versatility of this oxidative amidation approach, we tested the scope of the methodology with pyrazole-5-carbaldehydes 9 and 10

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• enynes 25a–e in yields up to 77%. Unfortunately, in the case of nitro-substituted enyne 25d only 4% were isolated due to rapid decomposition and instability issues (Table 1, entry 4). With enynes 25a–e in hand, the influence of solvent, reaction temperature, time, and Pd source on the hydrozirconation

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• , cyano, nitro, or halogenated groups at the para-position were crucial for activity [5][16][20]. Thus, compounds 1–3 with a para-phenyl-OCHF2, -Cl or -CN substituent at the C3 position of the triazole were selected as scaffolds in this study. In addition, the reported SAR data also indicated that the use

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• , trifluoromethyl and nitro substituents, were retained unchanged in the final products (3ja, 3ka, 3ma, and 3na). Also the strongly coordinating thioether substituent proved to be suitable for this protocol, providing the desired product 3ea in 76% yield. Moreover, under the standard conditions, 3-thienyl and 2

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• chiral aldehyde 127 and Boc-protected amine 128, followed by zinc reduction of the nitro group and subsequent protection of the amine by a tosyl group in 27% overall yield. Irradiating 129 with blue light at 30 W in the presence of 1 mol % of [Ir(dtbbpy)(ppy)2]PF6 and 5 equiv of KHCO3 in THF resulted in

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• with amino and nitro groups due to side processes on the electrodes. Cyclic carbamates were oxidized to lactams using ABNO derivatives as electrocatalysts [104] (Scheme 16A). The substrates with easily oxidizable pyrazole and oxazole fragments reacted successfully under these conditions. Under similar

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• . Stronger electron-withdrawing cyano group (3i) lowered the product yields to 20% due to low conversion of 3i. Introducing even a stronger electron acceptor, a nitro group (aldehyde 3j), led to only a trace amount of the respective product detected by 1H NMR analysis of the crude reaction mixture. Likewise

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• differed from the above path by leaving the hydroxy group of all intermediate 4-hydroxypyridine derivatives 12–15 unprotected [19]. Moreover, instead of azo coupling or nitroso formation, a simple nitration protocol with nitric acid to give the nitro derivative 13 and subsequent reduction with Raney nickel

• tert-butyloxycarbonyl-protected and deprotected 2-nitro-intermediates 20 and 21, respectively [23][24][25]. The nitro group was then selectively reduced using trichlorosilane and N,N-diisopropylethylamine (DIPEA) to form benzyl-protected 1-deazaguanine 22 [26]. Finally, the O6-benzyl moiety was cleaved

• was purified via silica gel chromatography using 0 to 4% methanol in dichloromethane as gradient. Yield: 395 mg of a mixture containing the 2-nitro-compound 20 and 21 (for NMR spectra see Supporting Information File 1). TLC: (5% acetone in toluene): Rf 0.34 (compound 20), Rf 0.05 (compound 21

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• resulted in the synthesis of derivatives 3 and 4, with 90 and 83% yield, respectively (Scheme 2). The C-28-propargylated triterpene esters (5 and 6, 70% yield for both) of the acetate derivatives (3 and 4) were obtained. Finally, the reaction of derivatives 5 and 6 with meta-nitro-substituted azide (c

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• later to make the synthesis more modular, and the resolution is straightforward late in the synthesis. Additionally, the presence of the nitro group in CPA 2 was chosen for two reasons: 1) the possibility to further functionalize at this position through reduction, diazotization, and metal-catalyzed