Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• in the asymmetric (3 + 2) cycloaddition of iminoethers with various 2-alkylidenecyclopentanones [53] In 2025, Wang and co-workers carried out a cascade enantioconvergent reaction between aldimine esters 1 and low-reactivity allylic alcohols 30, which are activated by oxidative dehydrogenation to form

• enones, which trigger a 1,3-dipolar cycloaddition via copper–ruthenium catalysis [54] (Scheme 15). Further reductive hydrogenation of ketopyrrolidines proceeds to form hydroxypyrrolidines 31 in high yields and excellent diastereo-/enantioselectivity. The reaction can be used with aldimine esters with

• . The authors used this methodology to modify peptides and functionalize several natural products. Thus, aldimine dipeptides Gly–Gly, Gly–Ala, as well as iminoesters in combination with natural ʟ-borneol, ʟ-menthol, cholesterol, or lactate scaffolds proved to be suitable precursors of azomethine ylides

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• , vinylogous Mannich reaction of the in situ-generated aldimine condensation product of 49 and amine 50 with trimethylsiloxyfuran 51 generated secondary amine 52 in a diastereomeric ratio of 10:1. To close the piperidine, which is to become the F-ring, six steps were carried out: 1,4-reduction of the

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• aryl group of the oxazaborolidinium ion is restricting the allyltributylstannane attack to only one enantioface of the imine C=N bond (Scheme 13, COBI–aldimine complex). The catalyst was used in the allylation of a wide range of aliphatic and aromatic N-(2-hydroxyphenyl)imines 64, providing good to

• active catalytic species in COBI-catalysed allylations, chemical equilibria in a solution containing catalyst 72, triflic acid, and aldimine 73 were investigated by low-temperature NMR spectroscopy (Scheme 15). Protonation of oxazaborolidine 70 with triflic acid resulted in an 8.3:1 mixture of 71 and 72

• chemical shifts of the Hb proton in 74 with the same signals in the free substrate 73 and protonated 75 at −40 °C. It was revealed that the aldimine proton Hb in the free imine appears as a singlet at 7.95 ppm, while in both 74 and 75 it becomes a doublet with a 15 Hz trans JH–H coupling constant. However

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• electromediated by iodine would furnish aldehyde 56. Electrogenerated iodine would further assist the reaction with ammonia to form N-iodo aldimine intermediate 57. Subsequent radical cycloaddition between 56 and 57 would furnish cyclic hydrazinyl radical 58. Finally, the triazole would be obtained after hydrogen

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• careful review of the product structure it was revealed that the purported dibenzodiazepine products were, in fact, diarylimines, which resulted from a nucleophilic addition of the aniline reagents to the aldimine substrates, followed by elimination of an tosylamine product. This was one of the principle

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• bioconjugates with different degrees of fluorescence labelling were synthesized as guests by controlling the feed ratios (Rf) of 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO) [23] to 2 mol %, 10 mol %, and 20 mol %, respectively. They were obtained with chitosan and TPE-CHO through an aldimine condensation

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• aza-Nazarov reactions of such imines were found to proceed successfully, albeit with slightly lower diastereoselectivities (ca. 4:1 to 16:1 dr) compared to their cyclic counterparts (Scheme 3). The reaction of the aldimine formed via the condensation of benzaldehyde and n-propylamine with acyl

• °C and with the use of 1.3 equivalents of AgOTf. Finally, we sought to check the reactivity of other substituents on the amine component of acyclic imine substrates. With the use of benzyl-substituted aldimine, the aza-Nazarov product 19l was obtained in 49% yield and with 10:1 dr. Similarly, the aza

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• configuration was not rigorously established, we have assigned it as the (E)-isomer, as is commonly observed in aldimine formation. The stage was now set for the key intramolecular aza-Prins reaction that would form the bicyclic structures of the halichonic acids (Scheme 2). When a solution of imine 7 in

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• cyclization leading to the formation of polycyclic azepino[5,4,3-cd]indoles. Synthesis of azepino[3,4,5-cd]indoles via iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides. Aldimine condensation/1,6-hydride transfer/Mannich-type cyclization cascade of

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

• cyanation of resultant aldimine intermediate to afford the α-amino nitriles (Scheme 20). This reaction worked well under eco-friendly conditions with low catalyst loading, and utilizing O2 as green oxidant to give excellent yields of the products. They also disclosed the efficiency of these Ru(II) complexes

• strategy. Proposed mechanistic pathway for the cyanation of the aldimine intermediate. Strecker-type functionalization of N-aryl-substituted tetrahydroisoquinolines under flow conditions. One-pot synthesis of α-aminonitriles using RuCl3 as catalyst. Synthesis of alkyl nitriles using (Ru(TMHD)3) as the

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• alkaloids that were isolated in the mid-1990s from the Caribbean sponge bataella sp. From a biological point of view, the batzelladines have received attention due to their reported activity as inhibitors of HIV gp120-human CD4 binding. Chiral N-tert-butanesulfinyl aldimine (SS)-58 was used as a precursor

• Grignard reagents to chiral aldimine (RS)-74, and an intramolecular oxidative cyclization of aminoalcohols derivatives 76, are key steps of this approach. Both diastereoisomers of aldimines 74 (RS and SS) were prepared from ᴅ-malic acid and the corresponding enantiomer of tert-butanesulfinamide

• the Re face of the imine with S configuration at the sulfur atom, through a chelated transition state. The reaction of chiral aldimine (SS)-104b with pentylmagnesium bromide gave compound 106 in 75% yield. Further successive N-desulfinylation, intramolecular palladium-catalyzed N-arylation, and final

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

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• Abstract This work describes an efficient, simple, and ecofriendly sonochemical procedure for the preparation of new α-(arylamino)acetonitrile derivatives C-substituted with phenothiazine or ferrocene units. The synthetic protocol is based on the Strecker reaction of a (hetero)aryl aldimine substrate with

• of aldimine and ketoimine substrates under mild conditions [18]. Early studies reported a positive effect of sonication on the classical aminocyanation procedures. The reaction rate of the classical Strecker reaction using cyanide salts, amines and aromatic carbonyl derivatives [19] or piperidone [20

• ] was customized for phenothiazinyl aldimine substrates (Scheme 1), but an extremely long reaction time was required (72 hours) for the reaction to complete. In order to enhance the reaction rate, alternative energy sources were taken into consideration and ultrasonic irradiation was selected as a green

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• -nucleophile; CF3-aldimine; fluorinated propargylamine; Introduction In recent years, substitution of hydrogen by fluorine atoms or fluorine-containing groups usually provides unexpected biological and physicochemical properties, which thus has become an established approach for the development of

• yne nucleophiles have never been reported thus far. Accordingly, intrigued by this methodological deficiency, we decided to dedicate a special research project to this objective; herein, we report Mannich reactions between yne nucleophiles and aldimine 1 (Scheme 1c). The results reported in this work

• excellent level (>90% de) of stereocontrol reported for the Mannich additions of aldimine 1 with sp3 [42][55] and sp2 [56] nucleophiles, including lithiated aromatics [57] one would not anticipate such a dramatic drop in the selectivity in the reactions of sp nucleophiles. Accordingly, we considered the

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• aldimines 62, failing to use unactivated educts [40]. Likewise, the α-silylated sulfonamide 67 was obtained in modest ee, although the chemical yield of the transformation was very low (15%). Changing the protecting group from Ts to methyl (68) or Boc (70) in the aldimine series did not alter yields or ees

Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms

• Erika Bálint,
• Anna Tripolszky,
• László Hegedűs and
• György Keglevich

Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40

• of alkylphenylphosphine oxides and the corresponding aldimine derivatives of thiazole 1 (Scheme 1) [12]. Cherkasov and his group applied the Kabachnik–Fields reaction to synthesize a P-chiral aminophosphine oxide with a 2-pyridyl substituent 3 (Scheme 2) [13]. Bis(aminophosphine oxide) derivatives

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• (Scheme 20b) [66]. Moreover, the Co-catalyzed hydroarylation of styrene with ketimine or aldimine proceeded without Grignard reagent using Mg metal as the reductant [67]. Recently, N–H imines 9d were also employed for the hydroarylation reaction with styrenes, giving a branched-selective hydroarylation

• . Indoles also efficiently participated in intra- and intermolecular hydroarylation reactions to access useful organic skeletons [70][71][72][73]. Thus, the reaction of indole bearing an aldimine and homoallyl group 29 in the presence of CoBr2, SIMes·HCl and Me3SiCH2MgCl gave dihydropyrroloindoles 30

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• addition to sulfinylimines is controlled by the formation of a cyclic, six-membered, chair-like transition state, which is formed by precoordination of the organometallic reagent to aldimine 5 [45]. This cyclic transition state accounts for the preferred re-face attack of the nucleophile at (S)-configured

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles

• Masahiro Torii,
• Kohsuke Kato,
• Daisuke Uraguchi and
• Takashi Ooi

Beilstein J. Org. Chem. 2016, 12, 2099–2103, doi:10.3762/bjoc.12.199

• reduced diastereoselectivity (Table 2, entries 1–4). Sterically demanding 2-tolualdehyde-derived imine 3f served as a good electrophile and the corresponding Mannich adduct 4af was isolated as virtually a single stereoisomer (Table 2, entry 5). 3-Thiophenyl aldimine 3g was also well tolerated, but a

• substantial decrease in diastereoselectivity was observed in the reaction with 2-furyl aldimine 3h, owing to the requisite higher reaction temperature (Table 2, entries 6 and 7). Catalysis with 1c was also applicable to aliphatic imines, which required prolonged reactions and slightly higher catalyst loadings

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• -nitrobenzaldehyde, and 2,6-dimethycyclohexanone for 8. The proposed reaction mechanism for piperidone formation is through an aldimine, which is formed by the reaction between an aldehyde and ammonium acetate. The aldimine is then attacked by a keto–enol to form a β-aminocarbonyl, which reacts with another molecule

• of aldehyde to form a second aldimine. Finally, 6-endo-enol-endo intramolecular cyclization leads to piperidone formation (Scheme 2) [58][59]. Structural and conformational analysis of piperidones 1–8 by NMR and X-ray diffraction Solution characterization of 1–8 was performed by 1H and 13C NMR, and

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• transformation significantly affected the selectivity in the desired products. Taking advantage of this secondary process, we performed a domino reaction, where the alcohol served as the source of both the nucleophilic radical and the aldehyde necessary for the in situ formation of the aldimine (Scheme 2, entry

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• , 25 °C for aldimine formation (first step) in the MM K-10 containing packed-bed capillary reactor (PBCR), and 80 °C for the reaction with phenylacetylene (second step) in Au NP@Al2O3 containing PBCR. The system, tested with some different aryl/heteroaryl/alkylaldehydes and cyclic/acyclic secondary

• diastereoisomeric 1,2-dihydroisoquinolines 40 (Scheme 22) [60]. Iminium intermediate 28, generated in situ from the aldimine 27 under silver triflate catalysis is the usual electrophilic intermediate, whereas the nucleophile, in this case, is the oxonium ylide 39. The reaction resulted in the synthesis of highly

• chiral phosphine ligands and AgOAc via bidentate chelation of a properly substituted aldimine. Chiral phosphine–silver(I) complexes are emerging as a valuable tool for carbon–carbon bond forming reactions. These catalysts are effective in promoting enantioselective allylations, aldol reactions, Mannich

Four-component reaction of cyclic amines, 2-aminobenzothiazole, aromatic aldehydes and acetylenedicarboxylate

• Hong Gao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 2934–2939, doi:10.3762/bjoc.9.330

• 1,3-dipolar intermediate A. In the meantime, the condensation of the aromatic aldehyde with 2-aminobenzothiazole affords an aldimine B. Secondly, the nucleophilic addition of 1,3-dipole intermediate A to aldimine B gives an addition intermediate C. Thirdly, the intramolecular nucleophilic attack of

Diastereoselectivity in the Staudinger reaction of pentafluorosulfanylaldimines and ketimines

• Alexander Penger,
• Cortney N. von Hahmann,
• Alexander S. Filatov and
• John T. Welch

Beilstein J. Org. Chem. 2013, 9, 2675–2680, doi:10.3762/bjoc.9.303

• control of the C–N ketimine geometry was reflected in the stereochemistry of the product β-lactam. Cyclization of imines with a stereogenic center bearing SF5 was reflected in the 1,2-lk,lk selectivity of the β-lactam. Keywords: aldimine; Cornforth transition state; diastereoselectivity; β-lactam; organo

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes

• Jing Sun,
• Hong Gao,
• Qun Wu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2012, 8, 1839–1843, doi:10.3762/bjoc.8.211

• enantiomerically enriched 4-amino-tetrahydroquinolines [43][44]. In this work our aim is to describe the domino Povarov reaction with both in situ formed aldimine and in situ generated β-enamino ester for the facile synthesis of the functionalized tetrahydroquinoline. Results and Discussion It is known that the

• was prepared in 63% yield (Scheme 1). The tetrahydroquinoline was obviously formed by the reaction of the previously formed β-enamino ester with in situ generated N-aryl aldimine. Thus, a domino Povarov reaction is successfully established. Similarly, various arylamines and aromatic aldehydes were

• published domino Povarov reaction [45][46][47][48][49]. At first, arylamine adds to methyl propiolate to form the β-enamino ester A. Secondly, excess arylamine reacts with the aromatic aldehyde to form the N-aryl aldimine B in the presence of p-toluenesulfonic acid as catalyst. Thirdly, the Mannich type