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

• -C(sp3)–H bond (21 examples, up to 53% yield). The methodology was applied to the functionalization of a series of amides having an α-quaternary center (α,α-dialkyl (31a), α-alkyl,α-benzyl derivatives 31c–f) as well as to an amide with an α-tertiary center (31b) and pleasingly, the presence of α-C–H

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• quaternary centers is tackled by the direct cycloaddition of allyl cation 90 across a tetrasubstituted olefin 95, at the same time elaborating the cyclopentane core of this natural product. The completion of this short synthesis also nicely showcases the use of dihydrodithiinmethanol 90 as a synthetic

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism. Keywords: decarboxylative cascade cyclization; iodide catalysis; metal-free photocatalysis; oxindole; phosphine catalysis; Introduction Radical-initiated cascade

• by these advances, we developed here a visible light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides under NaI/PPh3 catalysis, for the most efficient and practical synthesis of quaternary oxindoles (Scheme 1b and 1c). It should be noted that during the finalization of this

• derivative 3aa with 72% isolated yield (Table 1, entry 1). Other iodide sources, such as LiI, KI, RbI, CsI, CaI2, and a quaternary ammonium iodide, while also effective, provided slightly lower yields (Table 1, entries 2–7). It should be noted that all tested iodide sources were found soluble under those

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

• consecutive all-carbon quaternary carbon atoms [54][55][56]. Preliminary biological screening of this family revealed notable antibacterial and anticancer activities due to the α-methylene lactone moiety they bear [57]. Recently, in order to synthesize the common core present in crinipellins, Xie and Ding’s

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• ’-methoxy-γ-pyrone in one step. To construct the quaternary carbon of the 2,5-cyclohexadienone of the target, a strategy based on the Robinson-type annulation of an aldehyde derived from α-crotyl-α’-methoxy-γ-pyrone was applied. The grafting of the simplified target’s side chain was demonstrated through an

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

• ; Introduction The α’-methoxy-γ-pyrone motif is present in natural products and bioactive molecules [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Amidst these targets, a number contains a quaternary carbon vicinal to the scaffold, such as crispatene and photodeoxytridachione (Scheme 1a) [15]. These molecules

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

• active oxidative agent. Asymmetric quaternary ammonium phase-transfer catalysts proved to be effective in the asymmetric nucleophilic epoxidation of electron-poor alkenes by hydroperoxides [70] and the asymmetric hydroxylation of enolizable carbonyl compounds employing O2 or H2O2 as terminal oxidants [71

• -hydroxylation of lactams under phase-transfer organocatalysis conditions employing a chiral quaternary ammonium ion salt. Selective CH-oxidation of methylarenes to aldehydes or carboxylic acids. An example of the regioselective CH-amination by a sterically hindered imide-N-oxyl radical precursor. CH-amination

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• the 6-5-5 tricyclic skeleton includes the mediation of Nagata reagent for constructing the C1 all-carbon quaternary centers and gold-catalyzed cyclopentenone synthesis through C–H insertion. Keywords: aberrarone; C–H insertion; gold; Pauson–Khand; total synthesis; Introduction Marine natural

• , including two all-carbon quaternary centers, together with the non-enolizable cyclic α-diketone moiety collectively render aberrarone as an attractive but challenging synthetic target. Its congener elisabanolide (2) with a lactone in the D ring shows their potential biosynthetic relationship [2]. These

• one quaternary carbon stereocenter and 1,2-dikeone moiety, Nazarov cyclization [33] of 7 was proposed for synthesizing this challenging moiety. The corresponding precursor cyclopentenone 8 may be prepared from alkynone 9 through a gold-catalyzed C–H insertion [34]. Alkynone 9 could be achieved through

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• (1.46–1.47 Å) and quaternary ammonium salts (1.48–1.52 Å). Remarkably, in all 3N-TAADs (both with protected and free amino groups) two N-substituents are located in axial positions, while the third one is equatorial (Figure 2a–c, and e). Carbon–nitrogen bonds involving the nitrogen atom bearing an

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• no case, however, the ferrocenoylation reaction at the N6 position was observed in 1H NMR spectra. This is expected, as the nucleophilic addition pathway involving the quaternary ammonium intermediate is not viable. In all purine anions, according to the calculated Fukui functions f–, the N7 atom is

• (3). For some reason, the calculated barrier is prohibitively high (ΔG‡ = 144 kJ/mol), which suggests an inappropriate quality of the selected theoretical level, or indicates that an alternative ferrocenoylation mechanism in case of 3 is operative (e.g., the reaction which includes the quaternary

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• improve the yield of 2a (Table 1, entries 2–4). The present reaction proceeded in the presence of quaternary ammonium salts with different counter anions including the BF4 anion, and Et4NBr was found to be the preferable electrolyte among them (Table 1, entry 1 vs entries 5–7). Next, we examined the

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• , Supporting Information File 1) demonstrated the presence of one methyl, eleven methines (including ten aromatic ones), and seven quaternary carbons (including two carbonyl carbons). The structural information of 1 was further defined according to HMBC data (Figure S6, Supporting Information File 1). The key

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• -toluenesulfonate followed by reduction of the N-methylated quaternary ammonium salt 25 with sodium borohydride gave tetrahydroquinoxaline 26. Since N-amination of the latter with hydroxylamine-O-sulfonic acid [14] had been unsuccessful, we tried to achieve our target via the N-nitroso derivative 27, which was

• . Reduction of the quaternary ammonium salt 28 with sodium borohydride gave tetrahydroquinoxaline 29. Its reaction with trifluoroacetic anhydride (TFAA) to give 30 and removal of the benzyl group by catalytic hydrogenation afforded N-trifluoroacetyl-1,2,3,4-tetrahydroquinoxaline (31). Compound 31 was then

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• quaternary oxadiazole peaks appeared at around δ = 162.0 and 169.0 ppm. Compound 4f showed a carbonyl peak at δ = 196.7 ppm and for the carbaldehyde carbon in compound 4h a peak at δ = 160.8 ppm was observed. To further characterize the structures, 2D NMR experiments were done for compound 4p as example. The

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• displayed 26 carbon signals including two oxygenated carbons (δC 85.8 and 72.4), an oxygenated quaternary carbon (δC 79.5), and a glucopyranosyl unit (δC 101.9, 78.3, 77.7, 75.2, 71.9, and 63.0) (Table 3). These 1H and 13C NMR spectra of 4 were similar to those of ent-kauran-3α,12α,16α-triol except for an

• = 11.8, 5.7 Hz), 3.54 (1H, t, J = 9.3 Hz), 3.39 (1H, t, J = 9.3 Hz), and 3.28 (1H, ddd, J = 9.7, 5.7, 2.2 Hz)]. The 13C NMR spectrum of 5 displayed 28 carbon signals including two oxygenated carbons (δC 85.5 and 72.4), an oxygenated quaternary carbon (δC 79.6), a glucopyranosyl unit (δC 99.5, 75.7, 76.3

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• for two carboxyl carbonyl carbons (δC 175.1 and 171.1), two olefinic quaternary carbons (δC 141.1 and 128.1), two olefinic methine carbons (δC 149.7 and 123.5) and three methine carbons (δC 46.8, 40.7 and 29.8), one oxymethylene carbon (δC 67.0), three methylene carbons (δC 33.6, 26.7 and 22.4), and

• and 1.37, m, 1H; δH 1.84 and 1.64, each m, 1H), and an isopropyl group (δH 1.83, m, 1H, and δH 1.06 and 0.88, each d, J = 6.5 Hz, 3H). The 13C NMR spectrum (Table 1) consisted of signals for two carboxyl carbonyl carbons (δC 179.6 and 174.5), two quaternary carbons (one olefinic carbon, δC 150.2, and

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• Supporting Information File 1). When 1 equiv of EsY was added into the m-TPEWP5G solution, the resonance signals of EsY were shifted to upfield regions, which was caused by steric effects and electrostatic interactions between the quaternary ammonium groups containing m-TPEWP5 and the negatively charged EsY

Four bioactive new steroids from the soft coral Lobophytum pauciflorum collected in South China Sea

• Di Zhang,
• Zhe Wang,
• Xiao Han,
• Xiao-Lei Li,
• Zhong-Yu Lu,
• Bei-Bei Dou,
• Wen-Ze Zhang,
• Xu-Li Tang,
• Ping-Lin Li and
• Guo-Qiang Li

Beilstein J. Org. Chem. 2022, 18, 374–380, doi:10.3762/bjoc.18.42

• oxygenated sp3 secondary carbon (δC 76.3) and one oxygenated sp3 quaternary carbon (δC 74.2). As two of the six degrees of unsaturation were occupied by the double bond and carbonyl group, the remaining four unsaturations of 1 corresponded to a tetracyclic skeleton. The 1H,1H-COSY experiment (Figure 2

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• the basis of 2D NMR data. In the HMBC spectrum, the singlet methyl protons H3-17 and H3-18 show correlations to C-7, a quaternary carbon at 47.4 ppm (C-8), and an oxymethine carbon at 80.3 ppm (C-9). COSY and HMBC data established the alkyl chain from CH-9 to CH3-16. A correlation between H-9 and C-19

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• products we disclosed the efficient homocoupling of oxindole-based N-tert-butanesulfinyl imines, with the generation of chiral, quaternary 1,2-diamines in a mild and completely stereoselective way. The obtained 3,3′-bisoxindole derivatives were fully characterized by NMR and single-crystal X-ray

• because they can serve as key synthetic intermediates in the construction of complex natural products [17][18][19][20][21][22][23]. Particularly challenging is the placement of the two C3/C3’ contiguous quaternary stereogenic centers, just as they are found in various alkaloids, such as those belonging to

• corresponding quaternary 1,2-diamines were obtained. Instead, the presence of a substituent at the C4 position (4-Cl, 2g) hinders the course of the reaction, likely due to its spatial proximity with the reaction center, and no homocoupling could be observed. In order to rationalize the formation of bisoxindole

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• with nitrosoarene which provides facile access to chiral hydroxyamino malonamates having a quaternary carbon stereocenter (Scheme 1). Results and Discussion Initially, we chose the Takemoto catalyst to promote the model reaction between methyl N-bromophenyl-α-methylmalonamate (1a) and nitrosobenzene

Glycosylated coumarins, flavonoids, lignans and phenylpropanoids from Wikstroemia nutans and their biological activities

• Meifang Wu,
• Xiangdong Su,
• Yichuang Wu,
• Yuanjing Luo,
• Ying Guo and
• Yongbo Xue

Beilstein J. Org. Chem. 2022, 18, 200–207, doi:10.3762/bjoc.18.23

• 161.1), seven sp2 quaternary carbons (including five O-bearing aromatic carbons at δC 162.2, 156.4, 154.0, 153.5, and 141.5; and two aromatic carbons at δC 114.7 and 114.3), nine methine groups (δC 115.4, 143.7, 121.4, 106.5, 115.0, 144.2, 130.3, 114.2, 105.3), nine oxygenated methine carbon atoms (δC

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• . The 1H,13C-HMBC spectrum of compound 4a revealed that the methylene protons from the azetidine moiety and the 1,2-oxazole methine proton H-3, exhibited long-range correlations with quaternary carbon C-5 (Figure 2c). The aforementioned protonated carbons C-3 and C-3’ showed correlations in the 1,1

• -ADEQUATE spectrum thus allowing to assign a neighboring quaternary carbons C-4 (δ 109.9 ppm) and C-5 (δ 175.4 ppm), H–C(3)–C(4) and H–C(3’)–C(5), respectively. The 1H,15N-HMBC experiment revealed an expected long-range correlation between the 1,2-oxazole methine H-3 proton (δ 8.50 ppm) and nitrogen N-2

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• former two fragments were intervened by an sp2 quaternary carbon (C-4) substituted by an allylic methyl group (H-11) based on HMBC correlations from H-11 to C-3, C-4, and C-5. Another intervention by a methylene unit (C-8) to connect the second and third fragments was supported by HMBC correlations from

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• regio- and stereoselective γ-addition reaction of isoxazol-5(4H)-ones 103 to β,γ-alkynyl-α-imino esters 102 for the synthesis of axially chiral tetrasubstituted α-amino allenoates 104 containing an adjacent quaternary carbon stereocenter and an axially chiral tetrasubstituted allene scaffold [104

• phosphoric acid catalysis, we developed a highly regio-, diastereo-, and enantioselective dearomatization reaction of 1-substituted 2-naphthols 115 and β,γ-alkynyl-α-imino esters 100. The highly functionalized naphthalenone derivatives 116 with an allene moiety, exhibiting both a quaternary stereocenter and

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• cinchona alkaloid-derived quaternary ammonium salts (cat. 55) as the phase-transfer catalyst. The products were obtained in high yields (53–93%) with high enantioselectivities (40–76% ee) (Table 12) [46]. Lebrun et al. developed a new method to synthesize optically active isoindolinones via asymmetric

• aza-Michael/alkylation reaction catalyzed by cinchona alkaloid-derived quaternary ammonium salts. Asymmetric aza-Michael synthesis of isoindolinones. Asymmetric aza-Michael addition reaction catalysed by chiral bifunctional thiourea. Enantioselective 1,6-aza-Michael addition of isoxazolin-5-ones to p