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

• imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high

• -butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the

• -containing heterocycles; N-tert-butanesulfinyl imines; Intoduction Chiral imines derived from tert-butanesulfinamide have been extensively used as electrophiles in a wide range of reactions. The presence of the chiral electron-withdrawing sulfinyl group facilitates the nucleophilic addition of

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• tetraoxyspirophosphoranes to imines The addition reaction of the P–H bond of tetraoxyspirophosphoranes 199 to long-chain imines 200 of benzaldehyde, acetaldehyde, and dodecanal at room temperature generated the corresponding (α-aminoalkyl)spirophosphoranes 201 via the Pudovik reaction. The one-pot selective hydrolysis of

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

• a trifluoromethylated iminium ion 187 during the course of their studies on a Strecker-type reaction [123]. Starting from trifluoromethylated imines 193 or oxazolidines 194 and 195 bearing enantiopure chiral auxiliaries, the authors accessed the corresponding cyano derivatives 196–198 with different

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• imines 115, which led to alkylideneazetidines 116 (Scheme 52) [102]. The MgI2 acted as a Lewis acid and reducing agent, effecting the distal C–C bond cleavage in 113a to form an allenyl ketone, or an equivalent fluoro,iodo-enone species, either of which could then have added to the imine 115 and led to

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• of vinyl azides, or by other strategies involving oximes, imines and oxazoles [24]. One appealing strategy for the preparation of 2H-azirines involves the use of readily available vinyl azides [25][26][27][28][29][30]. However, the batch cyclization of vinyl azides into the corresponding 2H-azirines

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• review articles have been written about this topic, enclosing most of the advances made to date [3][4][5]. A fascinating subset of these transformations encompass the reduction of amides to imines, with direct subsequent functionalization. One of the methodologies for such a modification was developed by

• formamides [11] and reduction of isothiocyanates to thioformamides [12] by its means. There have also been some catalytic protocols developed for the reduction of amides to imines. The most notable examples incorporate iridium complexes and silanes [13][14]. Cheng and Brookhart showed that the chlorobis

• (cyclooctene)iridium dimer ([Ir(coe)2Cl]2) can act as the catalyst in combination with Et2SiH2 [15]. Surprisingly, they were able to obtain imines as well as amines using this methodology. Based on the works of Nagashima [16], an iridium-based protocol for tertiary amides was introduced by Dixon [17][18][19

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• report by Ishikawa and Kitazume that the reaction of anilines with tetrakis(trifluoromethyl)-1,3-dithietane (1) results in the formation of the corresponding imines of hexafluoroacetone [18]. Unfortunately, we were not able to confirm the structures by X-ray diffraction, and the structural assignment for

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• reaction undergo cycloreversion under the reaction conditions. Keywords: azomethine imines; cycloaddition; diazabicyclohexanes; diaziridines; regioselectivity; Introduction Cyclic azomethine imines (AMIs) are very useful synthetic blocks for the preparation of diverse dinitrogenated heterocycles by 1,3

• -dipolar cycloadditions under thermal or catalytic conditions [1][2]. In general, cyclic azomethine imines are classified into two types, depending on their structure: N,N'-cyclic AMIs with both nitrogen atoms included in the cyclic system and C,N-cyclic AMIs having the C=N motif in the cycle (Scheme 1) [3

• ]. A wide range of pharmaceuticals, agrochemicals, and other biologically active compounds are prepared using different types of (3 + n) cycloadditions, mainly with alkenes and alkynes [3][4][5][6][7]. For example, N,N'-cyclic azomethine imines are precursors of biologically active bicyclic

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

• expand our knowledge of the reactivity of imines and the origins of stereocontrol, as well as provide synthetic access to a series of trifluoromethylpropargylamine of high biological interest. Results and Discussion Drawing from our previous studies on the chemistry of trifluoromethylated sulfinylimine 1

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

• 139 (Scheme 19b). As previously mentioned, photoredox catalysis has been widely used for the generation of imines. The Jiang group applied this to the synthesis of substituted tetrahydroquinolines (THQs) 144 from α-amino acids 145 to give racemic products in good yields and found that the addition of

• and enantioselectivities (16 examples, up to 99:1 er). Within the same publication Jiang et al. expands this reactivity to activated imines 232, using slightly modified conditions to obtain α-amino ketones 233 in excellent yields and good enantioselectivities (10 examples, up to 95:5 er) (Scheme 35b

• intermediate 239•, which abstracts a hydrogen atom from TRIP-thiol to produce enantioenriched cyclic sulfonamides 239 in excellent yields and enantioselectivities (28 examples, up to 98:2 er). Chiral phosphates have also been used to catalyse the enantioselective nucleophilic addition of indoles 241 to imines

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

• reaction of trifluoroacetaldehyde hemiaminals with enolizable carbonyl compounds in the presence of a strong base [23], the reaction of aldiminium salts with (trifluoromethyl)trimethylsilane/Lewis base [24], and the preparation of secondary α-(trifluoromethyl)propargylamines from imines CF3CH=NR and

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• through treatment of 49a with trifluoromethanesulfonic acid in the presence of anisole to form 51. In a recent report, Fustero and co-workers synthesized a series of N-tethered 1,7-enynes 53 bearing fluorinated substituents starting from fluorinated tert-butanesulfinyl imines 52 (Scheme 27), which were

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

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• -dihydro-1,3,5-triazine-2(1H)-thione (6za). However, no product was detected starting from paraformaldehyde and paraldehyde. Presumably, this result could be either due to the aliphatic aldehydes' lower reactivity with thiourea to generate the intermediate imines undergoing ring-closure and subsequent

• alkylation, and/or due to the instability of the imines formed. In order to further explore the substrate scope of this multicomponent reaction, next we wanted to use other orthoformates. Interestingly, under the similar reaction conditions triethyl orthoformate (3b), tripropyl orthoformate (3c), and

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• subtle differences in the reaction conditions opened up distinct reaction pathways [1][2][3][4][5]. Imines are versatile substrates that can be converted into various azo compounds, depending upon the reaction conditions [6][7][8][9]. In particular, the reactivities of N-benzylidenes have been

• ]. Among these diverse applications, the Rueping group has reported excellent examples of the reductive umpolung homocoupling of imines and heterocoupling with α-amino radicals for the synthesis of symmetrical and unsymmetrical vicinal diamines (Scheme 1b) [23][26]. Notably, 1,2-diamines have widespread

• product 3a was unambiguously confirmed using X-ray crystallography [57]. To further extend the diversity of the reactivity of the imines in this process, we also attempted the use of a reducing agent in the reaction of 1a. Pleasingly, the reaction of 1a with 2 equivalents of the Hantzsch ester in CH3CN

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• )ethylene-1,2-dicarbonitrile (R = CF3) [8]. Both five-membered spirotetrahydrothiophenes 3 and seven-membered S,N-heterocycles (ketene imines) 4 were observed in the course of these reactions (Scheme 1). The latter products were trapped with suitable nucleophiles (R = CO2Me) or even isolated and identified

• -deficient ethylenes 2. Cyclic ketene imines 4 are also formed as products of formal [4 + 3]-cycloadditions. Formal [3 + 2]-cycloadditions of thioketones and [4 + 3]-cycloadditions of thiochalcones with donor–acceptor cyclopropanes 5 leading to tetrahydrothiophenes 6 and tetrahydrothiepines 7, respectively

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• -iminooxycyclohexadienones 28a,b (Scheme 12). Phenol (29) and 1-naphthol (30) were transformed into 4,4-bisoximes 31 and 32, respectively (Scheme 12) [35][78]. Imines 37–40 were obtained with good yields by the reaction of di-tert-butyliminoxyl radicals with primary and secondary amines 33–36 for several hours at room

• temperature in pentane or hexane (Scheme 13) [85]. Due to the low stability of most imines, they were not isolated in pure form but were transformed into 2,4-dinitrophenylhydrazones. For example, the yields of 2,4-dinitrophenylhydrazones from 37, 38 and 39 were 79, 68 and 78%, respectively [85]. The example

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• amines, imines, amides, pyridine nitrogen and pyrrole nitrogen or as oxidized nitrogen species, e.g., pyridine-N-oxides [10]. Díaz-Terán et al. examined the surface of the samples (surface groups, chemical state of the elements, metal content and distribution) during the activation process of

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• protocol for the radical alkylation of imines using ammonium alkylbis(catecholato)silicates 5.4 as the C(sp3) radical precursors (Scheme 5b) [50]. 4CzIPN (OD6) was found again to be the best organic photocatalyst, triggering the oxidative fragmentation of the bis(catecholato)silicate. The so-formed alkyl

• radicals occurs on the heteroatom and leads to versatile neutral C(sp3) radicals. Such processes can also occur via concerted proton-coupled electron transfer mechanisms [105]. Similarly, the photocatalyzed reduction of imines followed by protonation, as well as the reduction of iminium compounds, gives

• access to α-amino radicals [106]. Most approaches are based on inorganic photocatalysts. As a rare example of the use of an organic dye, Dixon and co-workers used eosin Y (OD13) to reduce imines and generate the α-amino C(sp3) radical upon protonation (Scheme 24) [107]. This radical is then trapped with

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• synthesized through alkylation of the benzophenone imine of glycine ester 73, with perfluorinated benzylbromide 19c or 2,4-bis(trifluoromethyl)benzyl bromide (74) in the presence of 2,7-bis[O(9)-allylhydrocinchonidinium-N-methyl]naphthalene dibromide, to afford the fluorinated phenylalanine imines 75a,b with

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

• 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

• dibenzylamines, and they have demonstrated scalability of the protocol (products in up to 3.8 g scale). Similarly, using Pd-TPFPP the oxidation of amines to imines was achieved in 88–99% yields with low loading (0.005 mol %, 13000 TON h−1) after 1.5 h of irradiation with visible light (Scheme 52) [97]. The

• oxidation of amines to imines was also described using heterogeneous catalysis. Zhang and co-workers demonstrated that the MOF (SnIV)porphyrin-containing photocatalyst (UNLPF-12) can be used for the oxidation of primary amines to imines in 88–99% yields under visible light irradiation (Scheme 53) [40]. In

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

• mechanism(s), a variety of substrates were suitable for this transformation, giving the desired products 42–44 in good chemical yields (Scheme 10) [32]. 1.2 Additions to imines Among the very first studies on Cu-catalyzed additions to imines one can include the work of Moeller and co-workers published in

• types of aldimines 47 to give both good chemical yields and enantioselectivities associated with products 48–51 (Scheme 12). However, these additions were not applicable to neutral imines or ketimines – they are best performed on activated imines (e.g., N-sulfonyl imines) [38]. The same year, Sato and

• co-workers [39] used a comparatively simple ligand to perform asymmetric silylations of imines. Different ethylenediamine-based ligands (L3–L5) were screened from which L3 proved to give even better yields and ees (Scheme 13). The use of this ligand was explored with other substrates 56 and found to

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• imines and the reaction rates were low for anilines and analogous compounds. However, using dichloromethane proved to be a more suitable solvent because of higher product solubility and the reactions could be followed using 31P NMR spectroscopy [98][102]. The addition of four molar equivalents of Ph2PCl

• appropriate pyridine carboxaldehyde 143 in refluxing ethanol/magnesium sulfate solution. The targeted ferrocenylphosphine imines 144 were obtained in almost quantitative yield. The α-ferrocenylethyl(dimethyl)amine 141 can be synthesized from ferrocenylethanol using phosgene and subsequent treatment with

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

• 66 with imines 65 for the first time, using aerobic conditions with a Cu(II) catalyst. EWGs on aldehydes gave a high yield of the product whereas the yield was decreased with EDGs (2,4-OMe, 4-Me, 5-Br, 5-Me and 4-Et ≤37%). Also, the reaction of unsubstituted benzaldehyde with substituted 2-AP gave

• that the presence of copper salt is mandatory for the formation of the fused heterocycle as its absence resulted in the formation of the enaminone only. The imines 118, generated in situ via the loss of nitrogen from azide derivatives, were found to be reactive towards 1,3-dipoles 117 to form diverse

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• imines 99 to furnish complex spirocyclic γ-lactams 101 (Scheme 29) [107]. These products show a trans orientation of the benzene moiety in the isoindolinone and the substituent in R2, according to NOE experiments and crystal structure analysis. The proposed mechanism involves an initial palladium

• of imines 99 with CO (23) and ortho-iodoarylimines 100. Palladium-catalysed three-component reaction of amines 2 with CO (23) and aryl iodide 105. Three-component reaction of 2-ethynylanilines 109, perfluoroalkyl iodides 110 and carbon monoxide (23). Ultraviolet-induced three-component reaction of N