Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• the synthesis of cyclic imines using a one-pot protocol involving Grignard addition to a cyano group followed by PhI(OAc)2 (Scheme 30) [51]. The authors used p-tolylmagnesium bromide for both the arylation of the unsaturated carbonitriles 55 and as a bromide source. Bromocyclisation was achieved using

• PhI(OAc)2, which formed a range of 5- and 6-membered bromomethyl cyclic imines 56 in good yields from unsaturated imines 57. Xia and co-workers reported the bromocyclisation of indole derivatives 58 (Scheme 31) using PIDA and CuBr2 as the oxidant and bromide source, respectively [52]. Racemic pyrrolo

• of cyclic imines 45. Synthesis of brominated pyrrolo[2,3-b]indoles 59. Bromoamidation of alkenes. Synthesis of brominated cyclic guanidines 61 and 61’. Intramolecular bromocyclisation of N-oxyureas. The formation of 3-bromoindoles. Bromolactonisation of unsaturated acids 68. Synthesis of 5

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• .20.241 Abstract An efficient and facile synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives was developed through the isocyanide-based multicomponent reaction of isocyanides, gem-diactivated olefins, and cyclic imines such as dibenzoxazepine, dibenzothiazepine

• great attention in biomedical applications, clinical diagnostics, and conjugate materials. Keywords: cyclic imines; dibenzothiazepine; dibenzoxazepine; isocyanides; multicomponent reactions; pyrrole; triazolobenzodiazepine; Introduction Pyrroles and their derivatives are important N-heterocyclic

• ]. Here, we report an efficient and facile approach for the synthesis of pyrrole-fused dibenzoxazepine, dibenzothiazepine, and triazolobenzodiazepine derivatives via I-MCRs of gem-diactivated olefins, isocyanides, and cyclic imines (dibenzoxazepines, benzothiazepine, and triazolobenzodiazepine) under

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

• reactants. Therefore, based on the previous studies on the oxidative 3-component Ugi–Joullié reaction [22][23][24] and our precedent experience [25][26][27], we speculated that cyclic imines could be good substrates for our reaction, thanks to their higher rigidity and stability. As depicted in Scheme 2b

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

• separate peaks on chiral HPLC. Kinetic resolution of chiral secondary allylboronates [15][30]. (E)-Stereospecific asymmetric α-trifluoromethylallylation of cyclic imines and hydrazones [31]. Hosomi–Sakurai-type allylation of in situ-formed N-Fmoc aldimines [32]. Chiral squaramide-catalysed hydrogen bond

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• ) [59]. Other catalysts In 2019, Vila, Pedro and co-workers reported a functional group-directed activation of the carbocyclic ring of indoles utilizing cyclic imines as electrophiles. The quinine-derived compound O1 was the catalytic reagent to functionalize the ortho-C–H bond of 4-, 5-, and 6

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

• , entry 4). The scope of the reaction with 3,4-dihydroisoquinoline substrates as cyclic imines was investigated under these conditions [35]. In the current work, we first opted to examine the activities of other Lewis acids in the aza-Nazarov cyclization of imine 5a with acyl chloride 6b. The reason of

• demonstrates the preparative value of the catalytic aza-Nazarov cyclization developed in this work. Following the success of the newly developed aza-Nazarov reaction with 3,4-dihydroisoquinoline derivatives as cyclic imines [35], we next opted to investigate its effectiveness with acyclic imine substrates. The

• of pure (E)- and (Z)-isomers. The aza-Nazarov cyclization of such diastereomeric mixtures always resulted in the formation of products as single diastereomers with cyclic imines (e.g., imine 5a) [35]. We initially attributed this observed diastereoselectivity to the reaction taking place only with

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• tetraamino-bisthiourea chiral macrocycles were synthesized [30]. When applied in catalyzing the decarboxylative addition of phenyl β-ketoacids to cyclic imines bearing sulfamate heading group, an interesting substrate-induced assembly catalysis mode was uncovered [30]. To expand more applications, herein we

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

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• analogs 9 [12], and homophthalic anhydride (10) [13][14]) and imines 11, 12 offers a route to substituted lactam molecules 13 and 14 [13][14][15][16][17][18][19]. Among them, the reactions of homophthalic anhydride (10) with Schiff bases 11 or cyclic imines 12 have been examined in detail (Scheme 1) [13

• [24]. It is also suggested that the imine substrate structure and the anhydride’s ability to undergo enolization have a profound influence on the reaction course [16][23]. While the reactions of homophthalic anhydride (10) and various cyclic imines 12 have been extensively explored [13][21][24][25

• ], there are only few reports featuring reactions between monocyclic anhydrides 5–9 and cyclic imines 12 in the literature [12][25][26][27][28][29]. Thus, it was shown that glutaconic anhydride reacts with 1-methyl-3,4-dihydroisoquinoline and with 1-chloroisoquinoline to give 11b-methylbenzo[a]quinolizin-4

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• at 78 °C, [4 + 2] cycloaddition took place between the o-QM generated from the corresponding aminonaphthol as diene component and cyclic imines playing the role of heterodienophiles (Scheme 5). Fülöp and co-workers then extended their studies by applying both 2-aminoalkyl-1-naphthols and 1-aminoalkyl

• -2-naphthols [81]. These bifunctional compounds were reacted with various cyclic imines such as 4,5-dihydrobenzo[c]azepine or 6,7-dihydrothieno[3,2-c]pyridine to have new naphthoxazinobenzazepine 44 and -thienopyridine 45 derivatives [82]. Transformations at 80 °C in 1,4-dioxane as solvent were

• polyheterocycles formed was also described. The [4 + 2] cycloadditions between cyclic imines and o-QMs derived from Mannich bases could also be successfully applied in the syntheses of natural alkaloid-like compounds 47. Osyanin et al. reported the preparation of rutaecarpine and evodiamine, the 14-oxa analogues

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• enantiomer (S)-63a to be achieved in 67% yield and 86% ee starting from the corresponding imine 60a (Scheme 24). This convenient methodology constituted a novel and simple approach to chiral fluorinated building blocks. In 2016, Pedro and Vila envisioned the first use of cyclic imines, such as

• (79–93% ee). Notably, even sterically hindered cyclic imines bearing two substituents were compatible, providing the corresponding products in high enantioselectivities (79–93% ee). Moreover, the use of ketimines in such reactions represented a challenge, owing to their low reactivity and steric

• ZnMe2 in ethyl acetate as solvent at 0 °C the enantioselective aza-Reformatsky reaction of seven-membered cyclic imines, such as dibenzo[b,f][1,4]oxazepines (X = O) and dibenzo[b,f][1,4]thiazepine (X = S) 70a–p [50]. As shown in Scheme 27, the reaction of these electrophiles with ethyl iodoacetate (47

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• [10]. The use of cyclic imines (or surrogates thereof such as isoquinoline [11]) in the CCR is quite scarce in the literature [12][13][14]. As an example, 1-pyrroline (in the form of its trimer 3) has been reported by Smith and co-workers [15][16][17] to condense efficiently with HPA analogs to

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• cycloalkanones using catalyst 11 [18]. The enantioselective synthesis of indolo- and benzoquinolidine compounds through aza-Diels–Alder reaction of enones with cyclic imines [19]. Enantioselective [5 + 2] cycloaddition [20]. Asymmetric synthesis of oxazine derivatives 26 [21]. Asymmetric synthesis of bicyclo

Diastereoselective Ugi reaction of chiral 1,3-aminoalcohols derived from an organocatalytic Mannich reaction

• Samantha Caputo,
• Andrea Basso,
• Lisa Moni,
• Renata Riva,
• Valeria Rocca and
• Luca Banfi

Beilstein J. Org. Chem. 2016, 12, 139–143, doi:10.3762/bjoc.12.15

• , no report of valuable diastereocontrol by them has appeared so far. Successful examples of diastereoselective Ugi reactions have been reported only with chiral amines [15][16][17][18][19] or with chiral cyclic imines (Ugi–Joullié reaction) [20][21][22][23], although in the latter case, racemization

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles. Keywords: ene-sulfonamide; imine

Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps

• Sambasivarao Kotha,
• Ongolu Ravikumar and
• Jadab Majhi

Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163

• -caprolactam from cyclohexanone oxime involving the BR. The activation energy for the BR is almost the same as that of the nucleophilic substitution at sp2 nitrogen. To synthesize various aza-arenes and cyclic imines, such as quinolines, aza-spiro compounds and dihydropyrroles, the intramolecular SN2-type

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , several cyclization strategies have been utilized in order to obtain cyclic constructs. For example, the incorporation of cyclic imines immediately gives cyclic MCR-products, whereas other strategies make use of unreactive, convertible or protected functional Ugi-substrates that can be cyclized via

• %). In addition, the mild conditions tolerate a wide range of Ugi-substrates, resulting in a broad range of different pyrrolidine mimics 32. A more straightforward method [53] includes a single Joullié-Ugi 3CR using previously described alkyl substituted cyclic imines [54] giving the cyclic constraint

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• ratio of the imines. This was true regardless of whether the hydrogenation catalyst (Pd, Pt, Raney-Ni) was pre-activated with H2 or not (for further details, see Supporting Information File 1). (Note: The reduction of a small number of cyclic imines with Pd/C has been reported, and showed a significant

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• polycyclic natural products, the successful employment of preformed cyclic imines was required. Accordingly, the imine 5a (Figure 2) was synthesised from commercially available 2-phenylethylamine [85] and reacted with the chromatographically inseparable mixture of diastereomeric Michael adducts 6a and 6a

• fundamental synthetic tool. Further development is ongoing in our laboratory and the results will be disclosed in due course. Biologically active natural products and drugs containing the piperidine ring. Cyclic imines employed in nitro-Mannich/lactamisation cascade. Thermodynamically driven epimerisation of

• /lactamisation cascade with in situ formed imines. Nitro-Mannich/lactamisation cascade of diastereomeric Michael adducts 6a, 6a’’ with cyclic imine 5a. Nitro-Mannich/lactamisation cascade with cyclic imines. aDiastereomeric ratio in a crude reaction mixture, bH2O/MeOH 1:1 mixture used as a solvent, cminor

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines

• Luca Banfi,
• Andrea Basso,
• Valentina Cerulli,
• Valeria Rocca and
• Renata Riva

Beilstein J. Org. Chem. 2011, 7, 976–979, doi:10.3762/bjoc.7.109

• membered cyclic imines. It allows the diversity-oriented synthesis of various tetrahydro[f][1,4]benzoxazepines. Keywords: benzoxazepines; cyclic imines; long range stereoinduction; multicomponent reactions; Ugi reaction; Introduction The Ugi reaction is probably the most renowned and widely used

• with chiral amines as auxiliaries [6], or with chiral cyclic imines. The use of cyclic imines (three-component Ugi–Joullié reaction) [7][8] is particularly useful, because the resulting Ugi products are necessarily nitrogen heterocycles. However, good diastereoselectivity has been obtained so far only

• be accessed stereoselectively from the three-component Ugi–Joullié reaction of cyclic imines. Results and Discussion We report here some preliminary results disclosing a new family of chiral 7-membered cyclic imines that afford good levels of diastereoselectivity when submitted to an Ugi–Joullié