Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• /bjoc.18.133 Abstract A series of N6-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The SN2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio (N7/N9-ferrocenoyl

• the acylation of purines from a regioselective to a regiospecific mode. Keywords: DFT; ferrocene; nucleophilicity; purine; steric effect; Introduction Nucleosides in which the sugar part is replaced with an organometallic moiety have attracted remarkable interest [1][2][3]. One important class are

• analogous reaction is regioselective and resulted in the formation of two products, i.e., N7- and N9-regioisomers (Scheme 1). In no case, the N1-, N3-, or N6-products were formed, which is comparable to the results reported for the reaction between benzoyl chloride (BzCl) and purine anions [25]. The two

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• reactivity and availability of multiple sites for substitution, often leads to an inseparable mixture of halogenated products [27][28]. Thus, a cheaper and sustainable method for a regioselective halogenation in a controlled manner is a worthy pursuit. In recent times, mechanochemistry [45][46], achieved by

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• regioselective 1,3-dipolar azide–alkyne cycloaddition to form 5-selanyl-1,2,3-triazole. The investigation of the biological activity of the compounds obtained in this study and the application of this synthesis route using other heterocycles, instead of imidazopyridine, are currently underway in our laboratory

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• , and double oxidative photocyclization. The photocyclization was a highly regioselective process. The molecular structures of DH-1 and DH-2 were confirmed by X-ray single-crystal analysis. Multiple intermolecular interactions, such as C–S, C–Se, S–S, S–Se, and Se–Se, were observed in the crystal

• packing structures of these compounds. Spectroscopic results and our previous work showed that the combination of molecular structure change and heteroatom replacement from S to Se could precisely modulate molecular energy levels. Keywords: crystal structure; double helicene; regioselective synthesis

• , regioselective double oxidative photocyclization was observed during the construction of three S-shaped double helicenes DH-1–3 based on thiophene/selenophene. From DH-1 to DH-3, sulfur atoms in the molecular framework were gradually replaced by selenium atoms. The crystal structures of DH-1 and DH-2 and

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• dimerization produces dispirocyclopentanebisoxindoles in a transition-metal-free protocol (Scheme 1). Results and Discussion There is extensive application of 3-phenacylideneoxindoles generating diverse reaction strategies following the regioselective and diastereoselective synthesis of carbocyclic and

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

• steps. In 2017, Lesyk and co-workers observed the indole C3 regioselective ring closure in the reaction between 4-aminoindoles 7 and acetone in the presence of hydrochloric acid as a catalyst (Scheme 4) [13]. Based on NMR spectroscopy and X-ray crystallographic analysis, the products were unambiguously

• assigned as 1-alkyl-3,5,5-trimethyl-5,6-dihydro-1H-azepino[4,3,2-cd]indoles 8. The authors proposed that aza-Michael addition of 4-aminoindoles 7 to in situ generated mesityl oxide gives compound 9 which undergoes a regioselective intramolecular cyclization–dehydration sequence to furnish 8. In 2019, Zou

• preference for cyclization onto the C5 position is more dominating than the higher nucleophilicity of the C3 position, making the CAr–C bond formation completely regioselective at the C5 position. Subsequently in 2017, Li and co-workers also applied the intramolecular Friedel–Crafts acylation strategy to get

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• study about the regioselective nucleophilic ring opening of C1-substituted OBDs 5 with water and alcohol and with an iridium compound as a catalyst (Scheme 1) [61]. Their study found the electronic nature of the C1-substituent controlled the regioselectivity of the reaction. Electron-donating groups

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• encountered in organic synthesis as precursors for the synthesis of nitrogen and oxygen-containing molecules [1][2][3][4][5]. The high reactivity caused by the polarization of the N–O bond enables the nitrosoarenes to undergo a wide range of transformations in a chemo- and regioselective manner [6][7][8]. The

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• solution (i.e., dichloroethane, 60 °C, 24 h, Ar atmosphere), 5 undergoes regioselective C-3 amidation with NFSI using catalytic amounts of K2CO3 [41]. An initial attempt to carry out the reaction by ball milling 5, NFSI (2 equiv), and K2CO3 (10 mol %) for 3 h afforded only traces of the aminated product 6

• + NFSI milled (bottom). (h) Analysis by ATR-FTIR spectroscopy of the reaction of 3a with NFSI. Regioselective C-3 mechanochemical amidation of 5 with NFSI. Supporting Information Supporting Information File 138: Experimental details, characterization data and copies of spectra. Acknowledgements We

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• was observed by TLC. However, the acid chloride reacted very sluggishly with (CH3)3SiCHN2, which is a safe alternative to the highly explosive diazomethane [34]. Another attempt to synthesize the open-chain precursor from indole and 2-bromo-N-(2-bromophenyl)acetamide by regioselective palladium

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• chemoenzymatic method was found to be superior over the chemical method in respect of the number of synthetic steps and overall yield of the final product. Keywords: bicyclic AZT analogues; bridged homoarabinofuranosylpyrimidine nucleosides; chemical pathway; Lipozyme® TL IM; regioselective enzymatic

• starting from diacetone ᴅ-glucofuranose were found to be 33.9 and 35.1%, respectively. In our earlier research work, bridged homolyxofuranosylpyrimidines were synthesized following a chemoenzymatic methodology where biocatalyst Novozyme 435 was used for regioselective acetylation of the primary hydroxy

• group present in 3′-O-benzyl-β-ᴅ-glucofuranosylpyrimidines [27]. In this article, regioselective acylation at the primary hydroxy group of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylpyrimidines was carried out with the different biocatalyst Lipozyme TL IM using the same acylating agent, i.e., vinyl acetate but

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• epoxide 7, the relative free energy of 7b is higher by 10.3 kcal mol−1 than that of 7a (Figure 5). Conclusion In summary, we successfully synthesized hydroxylated cyclooctane β-amino acid 6 and its derivatives 8, 10, and 13 starting from β-lactam 2. The regioselective synthesis of lactone 8, which is a

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• phthaloyl-protected N-terminal alanine was also used for macrocyclisation in peptide stapling [51][52]. Besides addressing the indole C2, the regioselective enzymatic halogenation at C5, C6, or C7 using FAD-dependent tryptophan halogenases opens a broad area of Pd-catalysed late-stage diversifications [53

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• of the anticancer agent verubulin. Thus, after regioselective 4-chloroquinazoline metalation by an in situ trapping metalation strategy, reaction quenching with iodine allowed us to isolate 4-chloro-8-iodoquinazoline in 83% yield. Surprisingly, further reaction of 4-chloro-8-iodoquinazoline with 4

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• radical 28 (Scheme 5). Regioselective Giese addition to the π-system 21 would generate the transient 2° alkyl radical 29. Due to the high energetic barrier associated with direct cross-coupling between sterically hindered 3° alkyl radicals and aryliron complexes, it is assumed the persistent aryliron

• an Fe(II) species and S2O82−, a cascade of SET reactions between the alkylcarbazate and the Fe catalyst will lead to the formation of the alkoxycarbonyl 125. Regioselective addition of the radical across the electron-neutral olefin will generate the radical intermediate 126, followed by the 6-endo

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• Shevchenko National University of Kyiv, Kyiv 01601, Ukraine 10.3762/bjoc.17.189 Abstract A regioselective method for the synthesis of 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones – close structural analogs of naturally occurring vasicinone alkaloids – is described. The procedure is based

• formation at the two competing nucleophilic centers. Results and Discussion In this work, we propose a regioselective approach to the synthesis of 2,3-dihydropyrroloquinazolin-5(1H)-ones 6 functionalized with a hydroxymethyl group by oxidative cyclization of hereto unknown 2-(buten-3-yl)quinazolin-4(3H

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• methodology based on the trans-stereoselective epoxidation reaction of 2,3-dihydroisoxazoles followed by the regioselective hydrolysis of the corresponding isoxazolidinyl epoxide [15][16]. Very recently, we have reported the synthesis of γ-(hydroxyamino)-α,β-diols by the addition of Grignard reagents to

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• ) through the regioselective hydroarylation of the carbon–carbon double bond. In TfOH, the reactions proceed further to 3-arylindanones, as products of the intramolecular aromatic acylation of the 3,3-diarylpropanenitriles by the electrophilically activated nitrile group [16][17]. Based on this study and

• -3,3-diarylpropenenitriles 2a–o as products of the regioselective hydroarylation of the acetylene bond (Scheme 1). These reactions proceeded only with an excess of AlBr3 (6 equiv). Thus, running the reaction of nitrile 1a with benzene under the action of less amount AlBr3 (1–4 equiv) resulted in an

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• corresponding plausible mechanism is shown in Scheme 19. Firstly, Au-coordinated alkyne undergoes regioselective hydration to form intermediate 48. Then, intramolecular nucleophilic attack by azide occurs to give 2-carbonyl intermediate 49. Subsequently, intermediate 49 will undergo aromatization as well as the

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• depending on the reaction conditions (Scheme 13) [53][58]. Cyclization of 4-cycloocten-1-ol (35) with Hg(OAc)2 resulted in formation of two types of fused bicyclic products, 9-oxabicyclo[3.3.1]nonane (36) and 9-oxabicyclo[4.2.1]nonane (37) (Scheme 14) [59][60]. It was observed that the regioselective

• enol ether derivative 79 forming carbocyclic compounds 81 with good yields via intermediate 80 [78]. The cyclization of compounds 79 undergo regioselective addition with the triple bond in exocyclic alkene position leading to the formation of α-mercury ketone 80, which were later functionalized by

• -metalation followed by a regioselective mercuri-cyclization reaction (Scheme 60). During the total syntheses of (±)-fastigilin C and (–)-fastigilin C (201), 2 equiv of Hg(TFA)2 were used to synthesize key intermediate tricyclic furan compounds 199, 200, and 203. Hg(TFA)2 helped in the desired ring-formation

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• the regioselective 2-functionalization of 1,3-dioxolane (13) with aryl chlorides 8. It was found that the electron-deficient aryl chlorides resulted in better yields within shorter reaction times over the electron-rich substrates. A possible catalytic cycle was shown to account for the reaction mode

• systems 16 were arylated in moderate to good yields. This photochemical C–H arylation protocol was also suitable for functionalizing diverse primary and secondary benzylic C–H bonds. The authors proposed a mechanism for this chemo- and regioselective C‒H arylation as shown in Figure 6 [62]. The

• corresponds to the observed major isomer product (Figure 15). In a related transformation, Hong realized the exclusively α-selective hydroacylation of ynones, ynoates, and ynamides via photoredox nickel catalysis. Thus, the combination of nickel and iridium catalysts efficiently catalyzed the regioselective α

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• recently found active against Parkinson’s and Alzheimer’s diseases [101][102][103]. In 2002, Jiang, while studying its synthesis, found the tris(indolyl)borane 154 instead of the desired chiral indole alcohol 155 while reacting the N-silylated 4-bromoindole 152 with n-BuLi in a failed regioselective ring

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• mixture of monometathesized products, but some dimetathesized (±)-9c was formed too. Similar to Table 1, G-2 provided the highest combined yield of (±)-9a and (±)-9b, but it was the least regioselective (ratio of (±)-9a and (±)-9b: 3.3:1 with HG-2, 2.5:1 with G-3 and 2:1 with G-2). We continued our

• (±)-15a and (±)-15b was formed as well. Judging from the ratio of (±)-15a and (±)-15b, HG-2 catalyst was the most regioselective and G-3 was the least regioselective. The next CM partner was 2,2,2-trifluoroethyl acrylate (7e, Scheme 9 and Table 9). With HG-2 catalyst, dimetathesized product (±)-16c was

• was formed, which was separable. The main product was always (±)-17a. HG-2 was more regioselective (ratio of (±)-17a and (±)-17b: 5:1 with HG-2 and 3.3:1 with G2), but G-2 provided a higher yield. We also attempted CM reactions of (±)-5 with 8-(allyloxy)-1,1,1,2,2,3,3,4,4,5,5,6,6-tridecafluorooctane