N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• itself, in which the carboxylic function acts as an ancillary hydrogen-bond donor for the direction of one of the reagents [9]. Amines serve as basic units and nucleophilic components capable of carbonyl compounds activation via enamine or iminium ion formation [10][11]. In particular, pyrrolidine became

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

• appears that in this case, both activation mechanisms, namely through hydrogen bonding and iminium ion formation are operating. Using the same chiral cinchona-based primary-tertiary diamine as catalyst (cat. 11), Zhai et al. developed a highly efficient intramolecular enantioselective aza-Michael addition

• 108 to aliphatic α,β-unsaturated aldehydes 109 and synthesized biologically active acyclonucleoside 110 via an iminium-ion activation mechanism. The initially formed product was reduced in situ to afford the final product in 82–89% yield and 89–96% ee (Table 25) [66]. In a similar method, Joie et al

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

• cation I and a CuI species. This process regenerated CuII in the presence of molecular oxygen. The deprotonation of the nitrogen radical cation produces an α–amino radical II, which was further oxidized to the iminium ion III to which the copper alkynylide added forming the desired product (Scheme 17

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• compound 16; the next step involves the formation of the iminium ion 17, which is then hydrolyzed to compound 8 and hydroxyacetaldehyde in the last step. Thus, the unexpected reactivity of 6a with diluted HCl may be explained by the electron-withdrawing effect exerted by the adjacent COOH group which

• facilitates hydrolysis of the iminium ion 17. Conlusion In conclusion, a straightforward and efficient method for the synthesis of new tetrahydroisoquinoline derivatives, 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids 7a–f has been developed. It is based on the Petasis reaction with the use

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

• addition of 4-hydroxycoumarin (1) by the Re face of the enones 2 through a bifunctional modified binaphthyl organocatalyst 18 with primary amine [37]. The reaction occurs through the activation of the enone substrate by formation of an iminium ion intermediate and, in the presence of an acid additive

• proposed transition state includes activations of the enone via an iminium ion and the coumarin by hydrogen bonding. A series of optically active polycyclic pyranocoumarin derivatives 37 was obtained in high yields with excellent enantioselectivities (up to 97% ee) (Scheme 12). Kowalczyk and Albrecht

• methodology developed made it possible to obtain a mixture of open and closed forms of (R)-warfarin (3a) from a bifunctional catalyst of squaramide by the formation of an iminium ion intermediate with enone and hydrogen bonding with hydroxycoumarin (Scheme 27a). By using the squaramide catalyst with tertiary

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

• aromatic substitution reaction. The substrate failed to give the same product when subjected to alkylation with the isolated putative iminium ion intermediate. The authors then suggested the reaction took place through a radical mechanism instead. This vanadium-mediated aminoalkylation reaction was found

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -proliferative activity against tumor cell lines leading to the discovery of new lead compounds (Scheme 6). A tentative mechanism in Scheme 7 depicts the formation of iminium ion A from the reaction between 19 and 20 after the intramolecular protonation by carboxylic acid. The A conformer stabilized by

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

• to give an imine in the first step, which is protonated by (S)-TRIP to generate the corresponding chiral CF3-substituted iminium ion. The latter subsequently reacts via the most accessible Re-face with indole 149 to afford the resulting Friedel–Crafts product 177. Worthy of note is the fact that the

• stabilization of radical 181 by the captodative effect could also favor the general process. Lewis acid activation of trifluoromethylated hemiaminal ethers has also been studied by Fuchigami et al. [115][116]. For instance, when 179b is treated with a slight excess of TiCl4 in dichloromethane, iminium ion 182b

• iminium ion 192 by Lewis acid activation was suggested by the authors (Scheme 46). The resulting CF3-substituted β-amino ketones 190 could then be efficiently transformed in a one-pot procedure into the corresponding CF3-substituted enones 191 upon Brønsted acid treatment. Langlois and Billard then

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• , irrespective of the site of activation, the subsequent ejection of the activating reagent would generate an extended iminium ion whose capture by adventitious water would produce legonmycin A directly. For context, the treatment of enol esters with oxidizing agents to give α-hydroxyketones, or halogens to give

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

• radical 5•, which (depending on the EWG) can either reduce another molecule of 2 via a SET process or via an atom transfer (AT) process and propagate the chain reaction [21]. The SET route directly generates 2• and iminium ion intermediate 6, but the AT goes through alkyl bromide 7, before generating 6

• reductively quenches the photocatalyst to form enaminyl radical 13•+. However, in this reaction 13•+ can then add to the alkene to give an alkyl radical 14•+, followed by hydrogen atom abstraction from the thiol, acting as a HAT catalyst, to give iminium ion intermediate 15. Hydrolysis of 15 generates the

• ]•+, with the latter oxidising 22 to give radical cation 22•+ and turn over the photocatalytic cycle. The radical cation 22•+ is then proposed to participate in a two-step electron and proton exchange process with [CoII] to give [H–CoIII] and iminium ion 24, likely via a [CoI] intermediate. [H–CoIII] can

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• non-nucleophilic anions can be isolated [14][15], but in organic synthesis, they are most often generated in situ from suitable precursors and are directly exposed to diverse nucleophiles. Such transformations have been achieved using CH2(CF3)NR2 as the iminium ion precursors [15

• of 1a and 2,3-dimethylbutadiene (DMBD), the regioselectivity of which is as expected for a highly asynchronous transition state with effective stabilization of the positive charge or a two-step ionic process (vide infra). The high electrophilic power of the 1-CF3-substituted propyn-1-iminium ion

• sequence. On the other hand, the successful thermal iminium-ion induced SE(Ar) reactions shown in Scheme 2 were not applicable to the iminium-substituted norbornadiene 2, which suffered undefined polymerization on moderate heating in various solvents. In contrast to so far unknown 9‑amino-9

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• diphenylphosphoryl azide (DPPA) in excellent yield. Finally, the oxazoline group, which acted as directing and protecting group, was removed in a three-step sequence of N-methylation, reduction of the in situ formed iminium ion and acidic hydrolysis. This afforded the azide-functionalized para-bromobenzaldehyde 3 in

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• chemical transformations come from this process, whose crucial step involves the formation of a charge-transfer complex between singlet oxygen and the amine. Subsequently, hydrogen-atom abstraction leads to the radical intermediate, which can undergo SET with a hydroperoxyl radical to afforded an iminium

• ion, then giving an imine after deprotonation (Scheme 50). Adopting this strategy, Che and co-workers obtained several imines in 90–99% yield from secondary amines [102] (Scheme 51). The authors observed that the oxidation is regioselective, occurring at the less substituted position of nonsymmetric

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction in photocatalysis, the oxidation of N-aryl tetrahydroisoquinoline (Scheme 31) [45]. Upon oxidation, the in situ-formed iminium ion was reacted with nitroalkanes, enamines, and indoles. In all cases, the 1-substituted tetrahydroisoquinolines were isolated in good to excellent yields. The reaction

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• , which is formed via initial acid-mediated electrophilic attack of the unsaturated lactone at C-2 of the pyrrole ring. The resulting carbenium ion should be stabilized as shown in Scheme 3 (B ↔ B’). Subsequent shift of the isopropyl group from C-2 to C-3 then would give carbenium(-iminium) ion C, which

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• ). However, the reaction was unsuccessful with aliphatic and low-boiling aldehydes (as the reaction was taking place at high temperature). The reaction mechanism involved a Cu-NPs-mediated C–H bond activation of the alkyne which further reacted with the iminium ion to form propargylamine 45 and Cu NPs were

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• carbocation. In the case of pyrrolidines, the carbocation is completely stabilized as an energy minimum in the form of an iminium ion and the reaction takes place in two steps. Keywords: alkanes; carbocations; DFT; oxidations; ruthenium tetroxide; Introduction Ruthenium-catalyzed oxidations [1][2] and, in

• not be located, the optimization of which led to P4b. Transformation of ion pairs into the corresponding products P4a and P5a,b was found to be essentially barrierless. As expected, the ion pairs identified as minima adopt the form of an iminium ion, the most stable being IN5b, corresponding to that

• bond and formation of the O–H bond but the resulting iminium ion was stable enough to be considered a real intermediate according to IUPAC definition of 1994, which is: “A molecular entity with a lifetime appreciably longer than a molecular vibration – corresponding to a local potential energy minimum

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• classed either as stabilised or non-stabilised, depending on the presence or absence of an electron-withdrawing substituent such as a carbonyl group. The most common method for their preparation is by condensation of a secondary amine with an aldehyde to give an iminium ion that loses a proton to give the

• N-alkylation of a pyridine [19][20][21][22][23][24][25][26][27], isoquinoline [26][27][28][29][30][31][32], or related structures [33][34][35], followed by deprotonation. Such ylides are formally azomethine structures assuming reactivity of the aromatic ring as an iminium ion, although the reaction

Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• component that leads to the formation of an imine intermediate A. The formed Schiff base is in equilibrium with its iminium cation B as a result of an intramolecular proton exchange with the carboxylic acid moiety which activates the iminium ion for the nucleophilic addition of isocyanide. Consequently, the

• electrophilic centre of the iminium ion in B is subjected to a nucleophilic attack of the isocyanide to furnish the intermediate C. Then, a second nucleophilic addition takes place at this nitrilium intermediate C with an intramolecular nucleophilic addition of the carboxylate anion. The final step is an acyl

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• anion. Next, a SET from the enamide 45 to Fe(III) affords again Fe(II) and a further reaction with the radical A or A’ leads to the formation of carbocation B or iminium ion B’, respectively. Recombination of these positively charged intermediates with the azide anion finally affords the oxyazidated

Anodic oxidation of bisamides from diaminoalkanes by constant current electrolysis

• Tatiana Golub and
• James Y. Becker

Beilstein J. Org. Chem. 2018, 14, 861–868, doi:10.3762/bjoc.14.72

• formation of mono- and dimethoxylated amides is well-documented in the published literature [1][2][3][4][5][6][14][17][23]. It is generally accepted that the initial electron transfer forms an iminium cation radical followed by deprotonation and further oxidation to generate an iminium ion/carbocation that

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• then react with Cu(II) to provide species such as Q or iminium ion S. Either of them would aromatize to generate the desired product 90. The alternate proposal involved a ligand exchange between Cu(II)X2 and dihydropyrimidinone 88 providing compound T, which gets oxidized in the presence of TBHP to

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• use of basic settings has been advantageous to primary glycamines synthesis [19]. Under basic conditions increased amounts of free-base ammonia are created, thereby favoring the nucleophilic attack at the carbonyl group. Moreover, the base helps deprotonate the iminium ion intermediate pushing the

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• , which then undergoes nucleophilic addition at the electrophilic iminium ion 4, eventually providing the A3 coupled product (Scheme 3). In the absence of the metal catalyst, the sp carbon (C–H) of the alkyne is less nucleophilic in nature. However, after the formation of the iminium ion 4 (as it happens

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• ] or LiAlH4 [65][66]. These reactions usually require mild conditions but the course of the reaction depends on the ease of formation of the iminium ion [48][67][68][69]. With the highly reactive LiAlH4, diamines can also be formed by reduction of the nitrile moiety [70]. This competition with the

• ]. The authors logically proposed that the decyanation occurred via the reduction of an iminium ion intermediate. The hydrogenation of α-aminonitriles catalyzed by nickel nanoparticles results in reductive decyanation and yields 29–31. The colloid solution of nickel is prepared in situ via reduction of