Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• efficient synthesis of diversely functionalized enamides 16 and 17, demonstrating remarkable tolerance towards various functional groups. In recent years, there has been a surge of research interest in coumarin derivatives due to their notable biological, pharmacological, and optical properties [16]. Zhou

• functionalized coumarin derivatives and related nitrogen-containing heterocycles, opening up exciting possibilities for their diverse applications in other fields. Similarly, the regioselective photodecarboxylative C–H alkylation of 2H-indazoles and azauracils using NaI/PPh3 as mediators and redox esters 3 was

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• derivative of alternariol, a heptaketide coumarin derivative with a fused tricyclic ring called dibenzo-α-pyrone [31][32]. Alternariol is one of the toxic metabolites isolated from Alternaria strains, that grow on various natural resources such as corn, rice, fruits, vegetables, oilseeds, juices, wins, and

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• nucleophilic attack of TMSN3 to deliver product 11 (Scheme 7). Tian and Chang et al. could synthesize 3‑sulfenylated coumarin compounds 13 by using N-sulfanylsuccinimides 1 under a Lewis acid catalysis system (Scheme 8) [48]. Additionally, oxidation of 3-sulfenylated coumarins utilizing (diacetoxyiodo)benzene

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• ketones 94 with ethers [81]. Contrary to what was obtained for the alkylation of coumarin at the carbonyl α-position, vinyl ketone undergoes Michael addition and ether addition at the β-position of the carbonyl (Scheme 20). The reaction delivered various alkylation products in good to excellent yields

• catalyst. The authors demonstrated that the introduction of the two indoles occurs in two distinct steps, a radical process and a Friedel–Crafts alkylation reaction. Coumarin and flavonoid derivatives are very valuable precursors in drug synthesis. In 2015, Ge et al. developed the regioselective and atom

• -economical CDC reaction of coumarin and flavonoids with different ethers through a C(sp3)–H activation process and obtained two novel ether-substituted derivatives (Scheme 24) [85]. This method can introduce ether substituents at the electron-rich α-position of coumarin and the β-H position of flavonoids. In

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

• well as ketones were compatible with this process. The chiral ligand L12 afforded the highest enantioselectivities of up to 98% ee (Scheme 12). Conjugate addition of Grignard reagents to coumarin (49) generated the corresponding magnesium enolates 50 [43]. In one instance, this enolate was trapped by

• of heterocyclic enolates 108 generated from coumarin and chromone [65]. The high enantio- and diastereoselectivity of these transformations were ensured by a Josiphos-type ferrocene ligand. The reaction of chiral metal enolates with onium compounds enabled the installation of structurally attractive

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

• this section, showcasing several diverse nickel-catalyzed domino reactions. In 2001, Rayabarapu and co-workers investigated the Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 1 with alkyl propiolates 2 for the synthesis of coumarin derivatives 3 (Scheme 1) [28]. The reaction

• undergoing reductive elimination to afford to [2 + 2] adduct, β-oxygen elimination followed by E/Z isomerization and intramolecular lactonization generates the annulated coumarin scaffold. In 2003, the Cheng lab extended on this Ni-catalyzed ring-opening strategy [31]. It was noted the addition of 1.5

• identical reactivity when exploring the Pd- and Ni-catalyzed asymmetric reductive ring opening of heterobicyclic alkenes, ultimately generating the bicyclic product 7 (Scheme 1) [32]. In 2003, the Cheng laboratory continued studying Ni-catalyzed routes towards coumarin cores through the Ni-catalyzed ring

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• ·5H2O and ascorbic acid as shown in Scheme 1. It was noted that an alkyne with an electron-withdrawing group 2c was found to be more reactive than an electron-donating group 2b in the formation of triazoloporphyrins. Similar to porphyrins, coumarin and its derivatives also possess diverse biological as

• well as optical properties. Moreover, the versatility of coumarin hybrids finds numerous applications including fluorescent brightening agents [16], optical sensors [17], organic light emitting diodes [18][19], light harvesting materials [20] and fluorescent probes in biological imaging [21]. Therefore

• , keeping the biological and optical properties of coumarin and porphyrin in mind, in 2015 we reported the synthesis and photophysical studies of β-triazole-bridged porphyrin-coumarin conjugates 11–15 [22] and β-triazolomethyl-linked porphyrin-coumarin dyads 16–20 [23] by using a click reaction approach

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• bromination of 2'-hydroxyacetophenone (product 2m, Scheme 3). Notably, easily oxidizable groups like –CHO remained unaffected under the reaction conditions (product 2k and 2l, Scheme 3). It is worthy to mention that the bromination on 2-naphthol and coumarin was extremely fast affording >95% yields within

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• process [40]. The first synthesis of coumarin by Perkin in 1868 was a breakthrough in the history of natural odorant synthesis [2]. Coumarin (46) has a sweet, slightly spicy, and hay-like scent [9][41]. It was extensively used in Houbigant: Fougère Royal (1882, appearing at approx. 10%), a perfume which

• has lent its name to a whole family of perfumes (fougère perfumes) [2]. Despite the molecular size of coumarin, it is often considered as a base note, but higher dosages can bring it into the middle notes. In 2015, Guo and co-workers reported a flow procedure for the synthesis of coumarin (46

• min. The authors propose that the reaction does not follow the mechanism of the Perkin process but proceeds via acylation of salicylaldehyde (44) to intermediate 45, which forms coumarin (46) in an intramolecular aldol cyclization. Therefore, O-acylation of salicylaldehyde (44) is completed at 150 °C

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• container as the noncovalent protective group, the Pitchumani and Srinivasan group also reported that the reduction of coumarin (18) by sodium borohydride could be site-selectively induced in the presence of β-cyclodextrin C (Figure 4c) [59]. The reduction site-selectively occurred at the carbonyl not the

• alkenyl site, producing the final 1,2-reduction product cis-O-hydroxycinnamyl alcohol 19. As a comparison, in the absence of the β-cyclodextrin host, both the 1,2- and 1,4-reduction products were observed. X-ray crystallography determined the host–guest complex of the coumarin and β-cyclodextrin, which

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• asymmetric organocatalytic methods to assemble biologically relevant compounds is highlighted by a review article devoted to the syntheses of coumarin derivatives [16]. Conjugated additions of stabilized nucleophiles are the cornerstone of organocatalytic methodology. Recent advances in this area are covered

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

• diversity of the secondary metabolites from the genus Wikstroemia. Keywords: coumarin glucosides; flavonoids; lignans; structure elucidation; Wikstroemia nutans; Introduction The genus Wikstroemia (Thymelaeaceae) contains approximately 62 species, which are widespread throughout the subtropical regions of

• identification of a new bis-coumarin glucoside 1, together with three known bis- and tricoumarin glucosides 2–4, two flavonoid glycosides 5 and 6, and eleven lignan glucosides 7–17 (Figure 1). Herein, we present the isolation and structural elucidation of these natural products and their in vitro biological

• absorption bands at 325 and 293 nm indicated the presence of a coumarin-type chromophore. The IR spectrum of 1 demonstrated absorption bands characteristic for an hydroxy group (3266 cm−1), α,β-unsaturated carbonyl group (1739 and 1701 cm−1), and an aromatic ring (1624 and 1457 cm−1). The 1H NMR spectrum of

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• Natalia M. Moreira Lorena S. R. Martelli Arlene G. Correa Centre of Excellence for Research in Sustainable Chemistry, Department of Chemistry, Federal University of São Carlos, 13565-905 São Carlos, SP – Brazil 10.3762/bjoc.17.128 Abstract Coumarin derivatives are essential scaffolds in medicinal

• , the advances in asymmetric organocatalyzed synthesis of coumarin derivatives are discussed in this review, according to the mode of activation of the catalyst. Keywords: asymmetric synthesis; green chemistry; 2H-chromen-2-one; organocatalysis; Introduction Coumarins are important naturally occurring

• plant constituents and display a wide range of pharmacological and biological activities, such as anticancer [1], antibacterial [2], and antifungal [3]. Moreover, coumarin derivatives have shown activity against neglected diseases as leishmaniasis [4], tuberculosis [5][6] and Chagas’ disease [7

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• -NH tryptophan. Notably, alkenylative ligation of tryptophan-containing peptides and alkynes containing biomolecular motifs including sugar, menthol, or coumarin units was successful, delivering unprecedented hybrid complex peptides 34d–f in good yield. Based on the developed intermolecular process

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• synthesis of coumarin (90) was also reported, which involved an intramolecular aldol-type condensation of the acetylated intermediate 89 derived from salicylaldehyde (88, Scheme 18) [125]. The initial O-acetylation step was telescoped directly into the next reactor; the two-step process gave an overall

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

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

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• reactions, including photopolymerization, photohydrolysis, and photodimerization [42][43][44][45][46]. Chemical transformations assisted by nanosized reaction vessels have gained attention in the field of supramolecular photocatalysis. Therefore, Sivaguru et al. performed the photodimerization of coumarin

• /22 ratio of 1:2, which revealed that the singlet spin-state of coumarin could be involved in the photodimerization process within the CB[8] cavity and that the triplet state could be shielded from external quenchers (O2 as a triplet quencher). These results also indicated that photodimerization could

The fluorescence of a mercury probe based on osthol

• Guangyan Luo,
• Zhishu Zeng,
• Lin Zhang,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2021, 17, 22–27, doi:10.3762/bjoc.17.3

• coumarin compound extracted from the fruit of Cnidium monnieri (L.) cuss [18][19]. Modern pharmacological studies have shown that OST has antihypertension, anti-epilepsy [20], anti-arrhythmia, anti-fatty-liver-disease, antitumor [21], antiosteoporosis, and other effects [22]. As a new type of fluorescence

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• and co-workers disclosed the palladium-catalyzed intermolecular carboxylative TMM [3 + 2] cycloaddition [36] (Scheme 3). Exposure of coumarin 61 to the silyl-substituted TMM precursor 62 in the presence of a catalytic amount of Pd(PPh3)4 afforded adduct 63 in 81% yield as a single diastereomer (Scheme

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• were inert to triazolations, surprisingly affords bromomethylcoumarin in the presence of AzPS and HBr. The reaction was optimized using salicylaldehyde (1 equiv) in the presence of AzPS (2 equiv) and HBr (2.0 equiv). The reaction afforded 6-(bromomethyl)coumarin (4a) in a yield of 78% (Table 2, entry 3

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• access various derivatives, such as 12 and 13, derived from the trapping and Baeyer–Villiger oxidation of 11, respectively, or compound 16, obtained via the ring opening reaction of 15 with an amine (Scheme 5). Taking the enolate intermediate derived from the addition of EtMgBr to coumarin as an example

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• coumarin 307 [71], Figure S1A, Supporting Information File 1 and Table 1), but the shift and intensity of the emission band did not change upon the addition of Cu2+. The reaction of 3a upon the addition of Cu2+ was also investigated by 1H NMR spectroscopy in order to obtain more insight into the mechanism

• yields of the derivatives 3a, 3b, and 4a were determined relative to coumarin 307 (Φfl = 0.58 in MeCN) [72] or rhodamine 6G (Φfl = 0.95 in EtOH) [71], according to the established procedures [88][89]. Synthesis Synthesis of the quinolizinium–spirooxazine conjugates 3a and 3b (E)-2-(2-(1,3,3

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• reported the synthesis of coumarin derivatives using photoredox catalyst 12 and CF3SO2Cl as a potent radical source [111]. In comparison to other reported methods, the reaction was carried out under mild as well as environmentally friendly conditions, and the reaction remarkably showed much tolerance for

• benzothioamides. Mechanism involved in the synthesis of benzothiazoles via oxidant-free C–H thiolation. Mechanistic pathway for the synthesis of coumarin derivatives via C–H cyclization. Plausible mechanism for the formation of 71 from 70. Proposed mechanism for C–H arylations in the presence of 12a and a Pd

• purines via dual photoredox catalysis. Arylation of substituted arenes with an organic photoredox catalyst. C–H trifluoromethylation. Synthesis of benzo-3,4-coumarin derivatives. Oxidant-free oxidative phosphonylation. Nitration of anilines. Synthesis of carbazoles via intramolecular amination. Synthesis

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• : DFT; F···H hydrogen bond; fluorinated phenylcoumarin; Pechmann reaction; through-space coupling; Introduction Coumarins constitute one of the big classes of naturally occurring compounds. The first coumarin was isolated from the tonka bean (Dipteryx odorata) in 1820 and, to date, more than 1300

• crystal structure and solution-state NMR data of the coumarin 6 were studied to examine any C–F···H–C hydrogen bond interactions. DFT calculations were performed to determine the preferred conformations of the structure that might exhibit a C–F···H–C hydrogen bond. Results and Discussion Synthesis of 2

• used for the synthesis of coumarins [42][43]. Methyl 2-fluorobenzoylacetate (3) was reacted with resorcinol (4) in the presence of H2SO4 at 35 °C, and 7-hydroxy-4-(2-fluorophenyl)coumarin (5) [39][44] was obtained as a light yellow solid. The last step of the synthesis was the methylation of the