Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• ]pyridine 7b was formed together with disulfide 18b and aminoborane 17b (Table 1, entry 11). We thus evaluated B(C6F5)3 as a nonmetallic catalyst to activate ammonia borane in the reductive hydrogenation of the C=N-bond in [1,3]thiazolo[4,5-b]pyridines 5 and 15c. In line with reports on the hydrogenation of

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• and C=O bonds of the indoxyl groups are somewhat longer than typical double bonds of these types (Figure 3). On the contrary, the C–N bonds in indigo are much shorter than the single C–N bond in pyrrolidine, while the lengths of the C–C bonds in the fused benzene rings are approximately the same as in

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

• review in 2018 focused on a variety of routes to these compounds [8]. The well-known Buchwald–Hartwig (B–H) and Chan–Lam (C–L) reactions have proven to be highly useful procedures that allow the step-economical synthesis of diverse biologically relevant heterocycles through C–N bond formation [9]. These

• diverse dibenzodiazepinones via a copper-catalyzed C–N bond coupling between 2-halobenzoates and o-phenylenediamines leading to a key intermediate that undergoes an intramolecular N-acylation to afford the corresponding dibenzodiazepinone structure in high yields (Scheme 1b) [14]. Another innovative

• was obtained in 15% yield along with the undesired dihydrophenazine 6 side product in 5% yield, produced by a further C–N bond coupling (entry 7, Table 2). We decided to decrease the amount of base and time, but little improvement was observed (entry 8, Table 2). Given the well-established role of the

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• trends observed on 13C NMR and IR spectroscopies for δ CS2 and ν̃ CS2 and support the hypothesis that the perpendicular arrangement between the CS2− and CCN+ units is retained in solution. Likewise, all the exocyclic C–C and C–N bond lengths in the crystal structures under examination were typical of

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• methods. Because there are one C=C bond and one C=N bond in the molecules 3a–m, no diastereoisomers are obtained. Therefore, the 1H NMR spectra gave simple absorptions for the characteristic groups in the molecules. For further developing the scope of the [4 + 3] cycloaddition reaction, MBH esters of

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• were extremely broadened. This can be explained by some equilibrium processes including internal rotation of the acetylamino group and/or exchange between C=N bond configurations. As the temperature increases, the width of the signals decreases, however, even at 100 °С, some signals remain broadened

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• under heating, followed by the formation of ylide, N–S bond cleavage, and C–N bond formation along with the release of N2. In 2019, Sun and co-workers introduced an unprecedented method for the synthesis of isothiourea derivatives via the activation of diaryl/alkyl disulfides 47 with N-halosuccinimides

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

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

• Dmitry B. Vinogradov,
• Alexei N. Izmest’ev,
• Angelina N. Kravchenko,
• Yuri A. Strelenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2023, 19, 1047–1054, doi:10.3762/bjoc.19.80

• in the thiazine ring leads to the cleavage of the triazine C–N bond. Further proton transfer gives product 9. The structures of the synthesized compounds 3a,b,j and 5a–k,m were confirmed by IR, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry. the potassium salts 3c–i,k,m were

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• electron-withdrawing groups on the aryl ring reacted smoothly with iodonium ylides to give the corresponding diarylamines with good to excellent yields. Also, secondary amines underwent N-arylation to deliver tertiary amines with moderate yields. Keywords: amines; arylation; C–N bond formation; iodonium

• strategies for C–N bond formation have been extensively explored by various research groups for the N-arylation of amines. Specifically, seminal contributions by Buchwald [15] and Hartwig [16] involving the use of palladium complexes as catalysts in the presence of either phosphine or diamine ligands for C–N

• bond formation. However, these methods suffer from limitations such as moisture sensitivity, the requirement of specific ligands, and the use of expensive palladium catalysts [17]. Also, Chan Lam, Evans, and other research groups have developed copper-catalyzed C–N bond formation reactions by careful

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• construction of tetrahydrofuro[3,2-c]pyridines is based on a Bischler–Napieralski cyclocondensation followed by the C=N bond reduction (Scheme 1d) [36][37][38][39]. Despite the simplicity of the latter approach and availability of 2-(furan-2-yl)ethanamine, the instability of intermediate dihydrofuro[3,2-c

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• formation of the terminal carboxamide in 6 might be due to a spontaneous C–N bond cleavage, which occurs in 1’’ prior to the cyclization, consistent with a mechanism recently proposed in photoxenobactin biosynthesis [34]. Despite the widespread occurrence of siderophores featuring a phenolic moiety with a

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• the C=N bond), diffusion controlled (the slope of the ln ipc vs ln v dependence is 0.48), and reversible; the direct and reverse peak separation value was 57 mV at 100 mV/s, and Ia/Ic peak current ratio was close to unity. This means that the radical anion of (GlyNi)L7 is stable, at least in the

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• norbornene derivatives 15 using imides 27 and tetraarylborates 28 (Scheme 5) [37]. The method utilizes C–N bond activation to trigger the reaction. The authors demonstrated a broad reaction scope. Electron-deficient amides were shown to perform worse than their electron-rich counterparts with the p

• alkene of the azabicycle producing 154. A C–N bond cleavage occurs creating π-allylrhodium 155. Subsequently, the phenol oxygen then adds to the π–allyl species in a cis fashion, furnishing 156 which is proposed to be the enantiodetermining step. The carbonyl–rhodium species 156 inserts into the alkene

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• benzylic substrates with azoles was developed [128] (Scheme 27). In the proposed mechanism DDQ participated in benzylic C–H bond cleavage. The C–N bond of the final product is formed as a result of the nucleophilic attack of azole on a benzylic cation. A two-fold molar excess of azoles was used. A

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

• , respectively. At this stage, we started to investigate alternative methods to cleave the amide via reduction. Achieving selective C–N-bond cleavage of amides under reductive conditions is still a largely unsolved problem since a C–O-bond cleavage is typically the preferred mode of reactivity, especially when

• using hydride reducing agents [13]. Nevertheless, specialized conditions for achieving C–N-bond cleavage of amides using SmI2 [13], Tf2O/Et3SiH [14], and stoichiometric Schwartz’s reagent [15] have been reported; however, none of these methods was successful in reducing amide 5 to the desired amine 4

• . Although there is one literature example of directly reducing a benzamide with diisobutylaluminum hydride (DIBAL) to achieve C–N-bond cleavage [16], we observed exclusive over-reduction of compound 5 under these conditions to form the corresponding N-benzylamine, even at −78 °C. We next investigated the

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• for the synthesis of 1,2-azaphospholidine 2-oxides/sulfides and their fused derivatives. The 1,2-azaphospholidine 2-oxide/sulfide derivatives have been prepared by construction of any of their ring bonds. Synthesis via C–N bond formation In 1962, Helferich and Curtius reported the first synthesis of a

• 1,2-azaphospholidine 2-oxide (γ-phosphonolactam) from N,N’-diphenyl 3-chloropropylphosphondiamide (1), which was cyclized to 1-phenyl-2-phenylamino-γ-phosphonolactam (2) in the presence of NaOH in methanol via the C–N bond formation (Scheme 1) [21]. In 1974, the strategy was applied for the synthesis

New synthesis of a late-stage tetracyclic key intermediate of lumateperone

• Mátyás Milen,
• Bálint Nyulasi,
• Tamás Nagy,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66

• (19a), a benzyloxycarbonyl group (19b) was also used for N-protection; (ii) compounds 19a,b were N-alkylated at the indole nitrogen atom with N-methylchloroacetamide to derivatives 20a,b; (iii) the 20→21 cyclization was realized by a Xantphos/Pd-catalyzed C–N bond-forming reaction; (iv) synthetic steps

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• known, but limited reports are available for reactions carried out under solvent-free conditions [28][29]. However, improving environmentally benign methods [30][31] of C–N bond synthesis is of enormous significance [32][33][34]. In comparison to the metal-mediated C–N coupling reactions [35], the

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• a further cycloaddition. In addition, the conjugation between the new C=N bond and the enol double bond promotes the enol tautomer formation. This may also explain why the trifluoromethylated 1,3-diketones produced the trifluoromethyl-substituted isoxazoles with lower yields than the methyl

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• form a salimethyloxazolinyl-thioester intermediate, which then undergoes a C–N bond opening resulting in an ester formation. Eventually, the thioester undergoes a hydrolysis reaction leading to compound 6. The compounds, which were discovered in this study, are members of the large family of nocobactin

Tenacibactins K–M, cytotoxic siderophores from a coral-associated gliding bacterium of the genus Tenacibaculum

• Yasuhiro Igarashi,
• Yiwei Ge,
• Tao Zhou,
• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku and
• Agus Trianto

Beilstein J. Org. Chem. 2022, 18, 110–119, doi:10.3762/bjoc.18.12

• conducted [24] (Figure 4). In the negative ion mode, a precursor ion m/z 654 underwent sequential eliminations at every hydroxamate C–N bond, giving rise to ketene-terminated product ions at m/z 621 and 421, which supported the position of hydroxylation at N37 and N26 and chain lengths of each cadaverine

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• residue (Figure 1C, step, i + iv → ii) [18][19][20]. Subsequent investigations validated the use of photoreactive boronic acids as an approach to reversible backbone N–H modification via photocleavage of an alkenyl C–N bond [16][17]. Traditional 2-nitroaryl groups allow cleavage of benzylic C–X bonds (e.g

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• , this synthetic method (nucleophilic aromatic substitution reaction) is crucial for the development of alternative C–N bond-forming reactions to conventional metal-involved cross-couplings, providing axially chiral N-arylcarbazoles 60 in good yields with remarkable enantiocontrol through a

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ). Enantioselectivity for a wide range of substrates was achieved in good yield with rigorous optimization of the reaction conditions by utilization of wild-type CAL-B. Synthetic N-glycosylation strategies for glycosidic C–N bond formation in 1,3-oxathiolane nucleosides This section will discuss the methods for

• carbon atom while maintaining α-configuration and simultaneous elimination of an acyl group as illustrated in intermediate IV. Further, attack of silylated cytosine on α-chloro-substituted derivative V in an SN2 reaction results in the formation of a glycosidic C–N bond in the β-configured nucleoside