Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• cinnamic acid. For example, Chen and co-workers (2020) reported the Pd-catalyzed N-acylation of cinnamic acids using tertiary amines to generate the corresponding amides 83 and 84 in good yields via C–N cleavage (Scheme 25) [61]. The active Pd0 species was inserted into the carboxylate group to afford the

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• + species, a process where transition-metal-based complexes are employed [29], often (in the case of Ru(II)-based derivatives) in the presence of tertiary amines as sacrificial reductants [27][28]. Nonetheless, while this work serves primarily as a preliminary study comparing the reducing power of various

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• compounds using dihalomethanes (Scheme 27) [79]. They developed a three-component reaction between amines (mainly tertiary amines), a dihalomethane, and a P(OH) species (like phosphonate, phosphinate, or secondary phosphine oxide) under catalyst-free conditions to afford α-amino phosphorus compounds 35. The

• DMSO or MeCN as solvents. The reaction works very well with tertiary amines (both symmetrical and asymmetrical) and with some bulky primary and secondary amines (such as n-octyl-, dibutylamine, and N-methyl-N-butylamine). When applying primary or secondary amines are used, milder reaction conditions

• , secondary alkyl group. Therefore, for primary and secondary amines, the N–H-bond cleavage takes place predominantly instead of the other two N–R cleavage possibilities. However, in the case of tertiary amines, the N–R cleavage depends on the stability of the carbocation generated. For example, when using an

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• to give 22. In a same manner, Opatz et al. have shown that zinc phthalocyanins can catalyze oxidative cyanation reactions of tertiary amines 23, yielding α-aminonitriles 24 under continuous-flow conditions [36]. This reaction proceeds through the excitation of zinc phthalocyanin by near-infrared

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• covered in this review are hydrogen-bond donors such as thioureas and squaramides, Brønsted bases such as tertiary amines, and Brønsted acids such as chiral phosphoric acids. As depicted in Figure 4, a bifunctional squaramide is able to activate both an α,β-unsaturated imine through hydrogen bonding with

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of N-aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which

• efficient methods for the synthesis of heterocycles by multicomponent processes and domino reactions [16][17][18][19][20], here we disclosed the oxidative one-pot four-step synthesis of 2-amino-3,3’-spiroindolenines using readily available tertiary amines, electron-rich anilines and isocyanides as starting

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

• products was concluded by the observed NOESY cross peaks between H2-H4 and H3-H4, clearly demonstrating the relationship between these three hydrogen atoms as cis. Formation of syn,syn-7a and -7b by the above tertiary amines would be mechanistically elucidated by the deprotonation of the most acidic H2

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• reactions. To increase the molecular diversity at the morpholine ring, tertiary amines were formed by nucleophilic substitution. A final removal of the cyclic ketal group in aq sulfuric acid provided spiromorpholinone derivatives 134a–e, 136a–e, and 138 (Scheme 37). Spiromorpholinones were evaluated as

• inhibitors of 17β-HSD3 in a microsomal fraction of rat testes. Their androgenic effect on androgen-sensitive cells LAPC-4 was also evaluated. According to the biological results, compounds 134 and 136 with substituents in (S)-configuration were better inhibitors than the (R)-isomers. Furthermore, tertiary

• amines 136a–e and 138 showed better 17β-HSD3 inhibition at 0.1 µM than the secondary ones 134a–e, with some of them presenting better inhibition values than the reference compounds (RM-532-105 and D-5-2). However, only morpholinones 138 that bear sulfonamide and carboxamide groups did not exhibit

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• team introduced a manganese(III) porphyrin system as a catalyst for the BH methodology to achieve C–N coupling reactions [43]. Various tertiary amines were isolated by coupling secondary amines and benzylic alcohols using Mn7 (3 mol %) in the presence of K2CO3 (20 mol %) under reflux conditions in

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• particular, Xu and co-workers used tertiary amines for achieving the reaction through a Pd/Cu co-catalysis [60]. The 17 examples were obtained by using PdCl2 (10 mol %) as catalyst and Cu(TFA)2∙H2O (30 mol %) as co-catalyst. At the end of the process the catalyst underwent reduction, and therefore, in order

• the other hand, Chandrasekhar and Sankararaman reported the same process starting from secondary amines instead of tertiary amines [61]. In this case, the catalyst system was Pd(OCOCF3)2 (10 mol %) and the oxidant Cu(OAc)2 (2 equiv) and oxygen. The reaction was carried out in toluene at 80 °C for 24 h

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• -diketone 2a. Supplementation of the reaction mixture with either a tertiary amine or inorganic base led to varying mixtures of mono- and difluoro products 2a and 3a, respectively, with the tertiary amines proving most effective. Inorganic bases offer the possibility of deprotonating 1a-enol to form a more

• reactive enolate 1a-enolate. Nitrogen-centered bases react with fluorine gas to form N-fluoroammonium fluorides and fluoride ion [49]. Thus, on addition of tertiary amines, fluorine can react to generate basic fluoride ions and deliver reactive, electrophilic N–F species. Given that Selectfluor is

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• introduced explicitly in 2019 [13]. Already in the presence of pristine SWCNTs 2, the ability of TEA 23 to catalyze enolate addition with 4 increased to A/D48/23 = 1.2 for a virtual catalytic complex 48 between the two (Figure 8). Covalent modification of SWCNTs with tertiary amines as in 49 further

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

• ]. They disclosed a reaction between acyclic iodonium ylides (e.g., 31/ I-10) and tertiary amines 32, which produced indoline rings 33 by forging two new C–C bonds between the ylidic carbon and unactivated positions on the amine (Scheme 5). In 2020, they disclosed a more complex variant of this reaction

• events. Xuan, Li and co-workers further investigated the coupling between iodonium ylides and tertiary amines, and showed that this thermal reaction could instead be initiated by blue light photocatalysis (Scheme 7) [124]. Therein, they investigated the iodoarene motif of the ylide, and while ylide 31

• synthesis from acyclic iodonium ylide 31 and tertiary amines. N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines. Indoline synthesis from acyclic iodonium ylides 39 and tertiary

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• electron-withdrawing groups on the aryl ring reacted smoothly with iodonium ylides to give the corresponding diarylamines with good to excellent yields. Also, secondary amines underwent N-arylation to deliver tertiary amines with moderate yields. Keywords: amines; arylation; C–N bond formation; iodonium

• , as well as secondary amines, underwent N-arylation with aryliodonium ylide obtained from 1,3-cyclohexanedione to furnish moderate to excellent yields of the corresponding secondary and tertiary amines, respectively. Representative examples of N-arylamines. N-Arylation of amines with hypervalent

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• functionalized various spiro[cyclohexane-1,3'-indolines] and related reactions. Results and Discussion Initially, the reaction conditions were optimized by using isatylidene malononitrile 1a and bis-chalcone 2a as standard reaction. Tertiary amines such as DMAP and DABCO did not catalyze this reaction (entries 1

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• 2021. Keywords: cyanation; nitriles; photocatalyst; ruthenium; tertiary amines; Introduction Nitriles are a major class of organic compounds having wide significance in materials science, agrochemical and pharmaceutical industry [1]. They are the privileged compounds finding broad applications in

• -immobilized ruthenium trichloride to catalyze the oxidative cyanation of tertiary amines [28]. The reaction was performed using 2 mol % of catalyst, 2.5 mmol H2O2, 1.2 mmol NaCN, and 1 mL CH3COOH in methanol at room temperature (Scheme 1). Better yields of the α-aminonitrile products were obtained for

• established a methodology for the oxidative cyanation of tertiary amines using a heterogeneous Ru/C catalyst [29]. Most of the reported works involve the use of toxic cyanating agents like NaCN or TMSCN. In this protocol, the authors have exploited the cost-effective, less toxic, and easily available ethyl

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• secondary and tertiary amines, amides/lactams/carbamates, and nitrile. The test reactions were monitored by thin-layer chromatography (TLC) and, where deemed necessary, results were further verified by GC–MS. The reagents employed encompassed tritylium tetrafluoroborate [50], H2O2/HBr [42], ceric ammonium

• /reagent combinations employed. The reaction of the secondary N-methylamine 2b with CBr4 [22] gave fluorenone (3) in 6% yield (determined by GC–MS), while tertiary amines, amides, and the γ-lactam 2e did not yield any. Formation of fluorenone (3) was also confirmed after applying a modified version of one

• amines 2c, 2d, and 2f, albeit in drastically lower yield (Table 1, entries 3, 4, and 6). Initially, our focus was on testing tertiary amines, as we speculated that the electrophilic iminium species 4a (R1, R2 = alkyl; Scheme 3) would form more easily with stabilizing electron-donating alkyl substituents

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ] discovered the photoinduced, copper-catalyzed cyanofluoroalkylation of alkenes and fluoroalkyl iodides 12. The reaction was initiated by the reduction of CuII with tertiary amines, which formed CuICN and an amine radical cation [55]. Under irradiation by ultraviolet light, CuICN was excited and transformed

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• bonds are not limited to tertiary amines/amides. Secondary amides could also be arylated, as reported by Montgomery, Martin and co-workers [72]. The authors discovered that the combination of Ir[dF(CF3)ppy]2(dtbbpy)PF6, NiBr2·diglyme, 5,5’-dimethyl-2,2’-bipyridine (5,5’-diMe-bpy), and K3PO4 in dioxane

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• , antipsychotic (12) [54], anticonvulsant (13) [55], and antiparkinsonian activities (14) [56][57] (Scheme 5A). A few years earlier, Hou and co-workers reported the very first metal-catalyzed C–H hydroaminoalkylation of tertiary amines using norbornene as the coupling partner [41]. For this method, the scandium

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• reaction works equally well with a CHF2-containing hemiacetal. Nitrogen-stabilized α-(trifluoromethyl)carbenium ions have also been extensively investigated. Under electrochemical conditions, trifluoromethylated iminium ions 182 were successfully generated by Fuchigami et al. [115]. Starting from tertiary

• amines 178a–c, the corresponding hemiaminal ethers 179a–c were obtained (Scheme 43). The reaction is highly regioselective as no methoxylation of 178a and 178b was observed on the nontrifluoromethylated alkyl substituent (Me or Et). Hence, although amines 178a–c are more difficult to oxidize than their

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

• dual catalytic mode. Ooi et al. reported an enantioselective synthesis of 1,2 diamines 247 from tertiary amines 248 and aldimines 249 (Scheme 39) [100]. The proposed mechanism involves a reductive quenching pathway with 248 to produce radical cations 248•+, which following deprotonation and a [1,2

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• tertiary amines and should only be carefully treated with reagents containing tertiary amino groups. Because of this, we were encouraged to examine EDC as a carbodiimide in the developed procedure (Table 1, entry 30). As expected, we found that the utilization of EDC in this reaction resulted in the

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• , first reported in 1834 by Liebig, which he named “melon” [119]. The material consists of two-dimensional sheets of hexatopic, hexagonal sp2-hybridised carbon and nitrogen atoms, linked by bridging tertiary amines (Figure 9) [120]. The material is crystalline as sheets are held together by strong π

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• step of the McKenna reaction. To this end, we used model compounds from our previous work, analyzed the possible side reactions, and proposed solutions in order to minimize or prevent the unwanted processes. We also showed that tertiary amines, that are commonly used as additives to prevent these side

• allyldimethylamine (pKa 8.72), respectively [44]. This effect was reinforced by the higher nucleophilicity of the nitrogen atom in 12 compared with Et3N, as we deduced by comparison of model tertiary amines: Me3N (in MeCN: N 23.05, sN 0.45) and Et3N (in MeCN: N 17.10, sN 0.52) [45][46]. On the other hand, the lower