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

• based on the operating transition states [37][38]. A cyclic transition state is proposed in the reaction with sodium borohydride. In this transition state, the oxygen of the sulfinyl group interacts with the boron atom, facilitating the release of the hydride, directing the attack to the Si-face of the

• solvent, metal and additives in 1,2-addition reactions to N-tert-butanesulfinyl imines of organometallic compounds, different transition models have been proposed to explain the stereochemical outcomes. The cyclic model justified by the Zimmermann–Traxler transition state [40][41][42] is the typical

• mechanism operating in reactions involving Grignard reagents in noncoordinating solvents, such as toluene and dichloromethane, while an acyclic model [43] is common in organolithium compounds in solvents such as THF. In the cyclic model, the bulky tert-butyl group occupies an equatorial position due to

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• given combination of enone and arylboronic acid. Keywords: asymmetric reaction; boronic acid; conjugated enones; chromones; enantioselective catalysis; Michael addition; Pd complexes; Introduction The asymmetric 1,4-addition of arylboronic acids to conjugated cyclic enones and chromones is a very

• (phosphines, NHC-carbenes, bisoxazolines, pyridine-oxazolines, and miscellaneous) is used. Review Catalytic systems based on phosphine ligands A pioneering work on the enantioselective addition of boron-derived carbon nucleophiles to cyclic enones was published by the group of Miyaura et al. in 2005 [32

• ]. Specifically, they have dealt with the addition of potassium aryltrifluoroborates to conjugated cyclic enones differing in ring size [32]. The catalysts PdL1a,b exhibited great conversion and enantioselectivities (up to 99% and up to 96% ee) for various combinations of nucleophiles and enones (Table 1). The

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• dicyanamide in refluxing butanol with modest yields (36–54%) [54]. The resulting compounds were tested as proton-conducting materials (Scheme 23A). Another example was reported by Pietras et al. who prepared a series of cyclic amines in order to access new metformin analogs with anticancer activity against

• demonstrated by Schenker and Hasspacher for the synthesis of potential blood sugar-lowering biguanides, derived from cyclic secondary amines (Scheme 32) [66]. Besides, Bernatowicz et al. showed in a methodological study that primary amines are more reactive toward N-amidinopyrazole than N-amidino

• mechanisms for this formation. The first one consists of a direct intramolecular addition–elimination of the triguanide into triazine (path A); and the second involves a tautomeric exchange and subsequent amine elimination from the cyclic aminal intermediate (path B). The isolation of the trisubstituted

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• -1,3-diol [21][22]. For instance, deoxoprosophylline (5) as a cyclic 2-amino-1,3-diol target molecule was prepared by Kokatla et al. in an 8 step synthesis starting from Perlin aldehydes, via Pd(OH)2-catalyzed reductive azidoketon cyclisation [23]. Another synthetic pathway involves a stereoselective

• synthesize novel, cyclic potentially analogues of sphingosine, incorporating a lipophilic natural pinane skeleton, starting from commercially available monoterpene-based allylic alcohols via a stereoselective hydroxyamination in the presence of a potassium osmate(VI) catalyst. We also planned to explore the

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• via formation of a 7-membered cyclic acetal 263 as a single isomer in nearly quantitative yield, followed by Lewis acid-catalyzed rearrangement leading to the formation of tetrahydropyran. Under optimized reaction conditions, TMSOTf gave 7-membered cyclic acetal 263, which upon treatment with TiCl4

• THP synthesis to complement the aforementioned 7-membered cyclic acetal strategy. The treatment of α-acetoxy ether 266 with Lewis acid produced the corresponding THP 267 with moderate diastereoselectivity in favor of the trans-2,6-stereoisomer, as shown in Scheme 63. A variety of 4-hydroxy-substituted

• . Formation of the oxocarbenium ion 289, followed by an intramolecular nucleophilic attack by the alkynyl bond on the cyclopropane unit gave cyclic oxocarbenium intermediate 290. Further, the attack of a halide anion (from TiX4) leads to the Prins cyclization to give bishalogenated bicyclic THP with all-cis

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• generally assumed that nucleic acid analogues require cyclic units in the backbone to generate the necessary conformational preorganization for duplex formation. This assumption does not hold true for GNA backbones where the destabilization caused by the shorter glycol moiety in DNA duplexes most likely

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• ]. The regioselectivity is controlled by the formation of a six-membered cyclic intermediate. Directing-group-assisted C(sp3)−H halogenation reactions are efficient for promoting regioselective C(sp3)−H halogenations (Scheme 1c) [24][25][26][27][28]. In these reactions, the C(sp3)–H bond at the β

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

• ; 4, Figure 1) [36][37]. The relevance of acridine in drug discovery galvanized Singh and co-workers [38] to develop a water-promoted three-component reaction involving aldehydes 5, cyclic 1,3-diketone 6 and ammonium acetate powered by microwave irradiation resulting in 4-arylacridinediones 7 in

• -fused tetrahydrodibenzoacridinones 9 using phenanthren-9-amine 8, aldehydes 5, and cyclic 1,3-diketones 6 as structural units in ethanol under microwave irradiation to result in the targeted products in excellent yields. A conventional heating used for the same protocol delivered the desired products in

• -ones 24 using substituted phenylenediamine 23, aldehydes 5 and cyclic 1,3-diketone such as tetronic acid 6c under microwave irradiation in aqueous conditions delivering the product in good yields (70–89%). The use of a non-polar solvent resulted in the formation of side products like benzimidazole

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• , MG, Brazil 10.3762/bjoc.17.66 Abstract Desulfonylative alkylation of N-tosyl-1,2,3-triazoles under metal-free conditions leading to β-triazolylenones is reported here. The present study encompasses the synthesis of triazoles with a new substitution pattern in a single step from cyclic 1,3-dicarbonyl

• many bioactive heterocycles [36]. These are also important precursors of diazo adducts which are used in insertion, cyclopropanation, and various rearrangements to construct various cyclic as well as acyclic moieties under metal-catalysed conditions [37][38]. On the contrary, under basic conditions

• ). This might also be attributed to the lower yields obtained in certain cases. It may be noted that the outcome of the reaction is highly dependent on the nature of the 1,3-dicarbonyl compound. In the case of cyclic-1,3-dicarbonyls, cyclopentane-1,3-dione 2b reacts smoothly in almost all cases whereas

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• the corresponding cyclic sulfate via the formation of a cyclic sulfite in the presence of catalytic RuO4. The reaction of this cyclic sulfate with a nucleophilic azide followed by the reduction of the azide group provided the target, 3-aminocyclooctanetriol. The second key compound, bromotriol, was

• stereospecifically new chlorocyclooctanetriols. Keywords: aminocyclitols; aminocyclooctanetriol; chlorocyclooctanetriol; cyclic sulfate; cyclitols; Introduction The synthesis of aminocyclitols has attracted attention because they contain substructures of many biologically active natural products [1][2][3]. They

• described in the literature [33] (Scheme 1). Among the most relevant precursors for the synthesis of aminocyclitols are cyclic sulfates [36][37][39][40] and they have been also used in the synthesis of C8-aminocarbasugars [36][37] recently. We envisioned that aminotriol 12 could be prepared by the reaction

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• corresponding acyclic or cyclic allylic amines in very good yields (see Supporting Information File 1 for details). Their subsequent α-deprotonation by LDA followed by treatment with chlorotrimethylsilane at −78 °C [81] resulted in clean C-silylation of the corresponding enolate providing silylacetamides 8a–m

• hexafluorophosphate (4) and TEMPO (3) were subsequently added to trigger the single electron oxidation of the formed amide enolates and radical oxygenation affording α-(aminoxy)amides 9a–n in good 51–77% isolated yields. Cyclic units in the allylic N-substituent (Table 2, entries 14 and 15) and the epoxide (Table 2

• chiral cyclic amide substituent on the nitrogen atom influences the selectivity of the radical coupling with TEMPO to some extent, though less than the 1-arylethyl groups. Somewhat surprisingly, amides 8h,i did not react with propylene oxide 7b neither at 0 °C nor at room temperature. In order to confirm

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• –426 nm (Table 2). P-methylated cation 5 exhibited the longest wavelength and the highest quantum yield. The electrochemical properties of benzonaphthophosphoindoles were investigated by using cyclic voltammetry, and the electrochemical data are summarized in Table 3 and Figure S4, Supporting

• plots of the HOMO−3 to LUMO of compounds 3 and 4. The calculations were performed at the level of B3LYP/LanL2DZ. Synthesis of benzo[f]naphtho[2,3-b]phosphoindoles. Selected bond lengths and angles. Absorption and emissions spectroscopy data.a Cyclic voltammetric dataa (E vs Ag/AgCl) and calculated HOMO

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• thermal addition of diazo compounds (the well-known carbene precursors), followed by N2 elimination. However, it occurs much more difficultly for diazo compounds than with singlet carbenes. This is due to the formation of a mixture of [5,6]-closed and [6,6]-open isomeric cyclic adducts. This phenomenon

• % yield [100]. Photolysis of derivatives of para-substituted 3-fluoromethyl-3-phenyldiazirones in the presence of C60 gave phenylmethanofullerenes 53–56 in acceptable yields (Scheme 17) [101]. The electrochemical properties of the products were characterized by cyclic voltammetry and differential pulse

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• temperature (35 °C) but toxic CH2Cl2 solvent (Scheme 1). The reaction using second-generation N-heterocyclic carbene ligands was faster and preferably yielded cyclododecatriene. Larger cyclic butadienes may be used in the production of flame retardants, lubricants and specialty polymers [149][150]. 3.1.3

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• . As can be seen from Scheme 2 the yields of the amination products 5 and 6 were dependent on the nature of the amine as well as on the used phthalazinone. Efficient results of coupling were received using, inter alia, cyclic, aromatic or benzylamines. The reaction of 3a with piperidine gave a higher

• transfer (MLCT), and intraligand charge transfer (ILCT) transitions were identified. The vis–NIR spectroscopy revealed that in complex 17 the metal-to-ligand stoichiometry is equal to 1:1. In turn, cyclic voltammetry was used to investigate the electrochemical behavior of complex 17. The measurements on a

• 2-chloro-N,N-dimethylethylamine and 4-(2-chloroethyl)morpholine and further palladium-catalyzed amination of lactams 3 with aliphatic, aromatic, benzylic, cyclic amines and polyamines. Furthermore, we have demonstrated that some of the phthalazinone derivatives act as ligands and form stable

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• first protein-biosynthesis-generated structures are based on variable backbone elements; proline (cyclic and chiral), glycine (acyclic and achiral) or alanine (acyclic and chiral). Subsequent acquisition of the functional side-chains for this repertoire led to the recruitment of amino acids that are

• elucidate three-dimensional structures of proteins. However, the substitution of proline by one of the remaining 19 coded amino acids can be harmful to protein folding and the functional properties. This is usually explained by the absence of the amide hydrogen atom and the cyclic nature of the proline ring

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

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• Chemistry, Russian Academy of Sciences Leninsky prosp. 47, Moscow 119991, Russian Federation Department of Chemistry Johannes Gutenberg-University, Duesbergweg 10–14, D-55128 Mainz, Germany 10.3762/bjoc.17.27 Abstract The Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic 1,3-dienes was

• mol−1 for endo-1h and 121.75 kJ mol−1 for exo-1h and were consistent with the predicted ones. Next, the reaction with some other cyclic dienes was investigated. The reaction with the unsymmetrical 1-methoxy-1,3-cyclohexadiene (Scheme 5) led to the formation of a mixture of four products (regioisomers

• (H5 or H6) and its coupling constant to fluorine (3JH5-F or 3JH6-F). The reaction with 7- and 8-membered cyclic dienes (1,3-cycloheptadiene and 1,3-cyclooctadiene) did not result in the formation of the corresponding cycloadducts confirming that the reaction is very sensitive to the structure of the

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• the metal ions localized at different sites of the molecule. Electrochemistry studies Cyclic voltammograms for new o-quinones have been recorded in CH3CN solution containing 0.10 M (n-Bu4N)ClO4 as supporting electrolyte at a glassy carbon working electrode and a Ag/AgCl/KCl reference electrode. Table

•  1 summarizes the results of the electrochemical studies. Usually, the electrochemistry of sterically hindered o-quinones is relatively simple, it includes two one-electron steps with separation of potentials. Cyclic voltammetry studies reveal that the reduction of 3a, 6a and 7 takes place in two

• a Bruker Avance III 400 MHz instrument with TMS as an internal standard. EPR spectra were obtained using a Bruker EMX CW X‐band EPR spectrometer. Cyclic voltammetric measurements for new o-quinones were performed in MeCN in argon atmosphere on the Elins P-45X instrument using a glassy carbon working

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

• , we have performed a number of different functionalizations of such cyclic systems with various complexity, and with a particular focus on the modification of sugar-derived lactams. As summarized in Scheme 1, this includes simple nucleophile addition to in situ-generated imines [23], the consecutive

• spontaneous decomposition of the zirconium complex INT-1-A to the free imine species INT-3. This process is much more likely to occur via the 5-membered cyclic transition state TS-1-A than the alternative TS-1-B, as the energy barrier of 60.1 kcal·mol−1 is definitely too high for the reaction to take place

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• acid (GCP) or the aminopyridine carbonyl pyrrole carboxylic acid (ACP). At low temperatures, small cyclic structures are formed. However, at elevated temperatures, a ring–chain transformation leads to the formation of a supramolecular polymer. We demonstrate that this effect is dependent on the

• interact with each other and form cyclic structures. At increased temperatures, a ring–chain polymerization takes place and the monomeric compounds undergo supramolecular polymerization, leading to a viscosity improvement in chloroform. In this study, it was also shown that LU needs to have a

• precoordinating effect to favor the cyclic form at lower temperatures. Thus, the alkylene-bridged monomer A shows no effect in terms of viscosity improvement. In contrast, the gem-dimethyl unit in monomer B leads to sufficient stabilization of the cyclic form at lower temperatures. This allows a ring–chain

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• % overall yields. A relevant consideration in Holmes’s synthesis is: the nitrone is the same common intermediate as Gössinger’s [25], which is cyclized to form the tricyclic adducts. While the Gössinger route started from the cyclic 1-hydroxypiperidine, Holmes performed in situ cyclization to prepare the

• ]D24 +7.43 (c 0.350, MeOH); {lit. [α]D +7.5 (c 2.0, MeOH), [26]}. The (−)-adaline precursor (+)-23b was also accessed from 17 in 5 steps, in an overall yield of 7.3%. Inspired by Gössinger’s work, Murahashi et al. prepared a nitrone from a cyclic amine. However, the route was improved by the

• (−)-79a and (−)-79b, which were oxidized to enone (−)-80. The enone (−)-80 was subjected to ring-closing metathesis with Grubbs second-generation catalyst resulting in cyclic enone (−)-81 in 74% yield. (−)-81 was treated with phenylselenol to generate selenide 82 in high yield. The ozonolysis of 82 was

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• reactions, which allow for structural modifications on the organic compounds by forming several chemical bonds in one pot. To this end, gold catalysis [1][2][3][4][5][6][7] has been widely exploited to construct various cyclic and heterocyclic frameworks through cascade reactions triggered by the activation

• species to the alkyne 5, as in I (Figure 2). The first step TS1 has a low activation energy (ΔG‡ = 12.2 kcal⋅mol−1) to form the unstable cyclic intermediate II. This short-lived species rapidly reopens through TS2 (ΔΔG‡ = 8.1 kcal⋅mol−1) to give the pentadienyl cation III, which presents a high stability

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• -workers proposed that the catalytic mechanism involves a reaction between phosphine catalyst A and allene 82 to give B and/or C (Scheme 5B). Catalytic [3 + 2] cycloaddition of B and/or C and alkene D gives the cyclic intermediates E and F in an equilibrium state through a 1,2-proton transfer. The loss of

• ). An intermolecular [3 + 2] cycloaddition of tetrasubstituted alkene 150 and the dhdt-2-methanol reagent 151 under the effect of trifluoroacetic acid produced adduct 154 in 52% yield. The authors identified that the cyclic nature of the dhdt-2-methanol reagent 151 is essential for the cycloaddition to