Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• advantages over the related enol silyl ethers [24][25]: they are more stable towards acidic conditions, their electronic character contributes to high regioselectivity in cycloaddition reactions, and they can be converted to many other functions, including their hydrolysis to ketones [26]. In the other hand

• , we have shown that the Wightman reagent 6, a chiral chloronitroso derivative [27], led to a complete regio- and stereoselective reaction with functionalized dienes (Scheme 1). The chiral auxiliary contributes to both regioselectivity and stereoselectivity. After hydrolysis of the chiral auxiliary and

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

• at the exocyclic amino group of adenine affect the reactivity of the respective purine anion and govern the regioselectivity of the ferocenoylation reaction (N7- versus N9-product). By using an appropriate substituent at the C6 position in the purine ring, one can tune the isomeric product ratio, i.e

• . may influence the regioselectivity of the ferrocenoylation reaction. While the N9-position of the purine ring is a typical site of substitution, the N7-position may be preferred in some situations. In any case, the interplay between steric and electronic effects of selected substituents is crucial to

• different regioisomers, 1-N7 and 1-N9, were formed simultaneously in the course of the reaction between adenine anion 1 and FcCOCl in DMF (Scheme 1). According to the 1H NMR spectrum (Figure 1) of a reaction aliquot, the ratio of N9/N7 isomers is 1.5:1, i.e. 60% regioselectivity is reached. The formation of

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis

• thermodynamic stability (1.3:1, see Supporting Information File 1). Notably, the coordination to the Lewis acid increases the regioselectivity of protonation in the allylic anions formed in the electrolysis. Thus, using LiCl as a supporting electrolyte increases the ratio to 5:1. An even more pronounced effect

• in the side chain; the regioselectivity can be tuned by the addition of Lewis acids. This type of non-proteinogenic amino acid derivatives is not easily available but strongly required due to their bioactivity. One-pot nucleophilic in situ functionalization of the double bond of dehydroalanine

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• trace amount of 3 was detected by HRMS analysis (Figure S8, Supporting Information File 1). Redox partners might be responsible for the different regioselectivity between in vivo and in vitro reactions, as it has been reported that different reductases would lead to different diastereomeric dimers of

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• ‐substituents, and others suffer from poor regioselectivity for substrates without a directing group [18][19][21][22]. On the other hand, methods based on metal-free [23], palladium- [24][25], and copper-promoted [26][27][28][29][30][31] intramolecular N-arylation of in situ-generated or isolated o

• -haloarylhydrazones are advantageous concerning regioselectivity. However, they also present limitations, such as costly Pd catalysts, a scope of the N-substituent limited to alkyl [30], (substituted) phenyl [23][24][25][26][27][28][29], and tosyl moieties [31], and low to moderate yield when o-chloroarylaldehydes or

• seen in the 1H NMR spectrum. This inversion of the regioselectivity can be attributed to electronic and steric effects of the N-substituent but needs additional investigation for full comprehension. When arylhydrazone 1i or 3i, respectively, was subjected to the same reaction conditions in the absence

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

• of N-halosuccinimides (NXS, X = Br, I, and Cl). It was observed that PEG-400 plays a key role in controlling the reactivity of the substrates and to afford better regioselectivity. Almost exclusive para-selectivity was observed for the aromatic substrates with free o- and p-positions for mono- and

• reaction time, and mild reaction conditions are a few noticeable merits of this environmentally sustainable mechanochemical protocol. Keywords: automated grinding; chemoselectivity; mechanochemistry; N-bromosuccinimide; PEG-400; regioselectivity; stoichiometry-controlled halogenation; Introduction Aryl

• in good yields (product 2ai and 2aj, Scheme 3). It is worthy to note that PEG-400 as the grinding auxiliary not only expedited the reaction but also played a key role in availing better regioselectivity. A very high para-selectivity was observed for both phenols and aniline substrates with free o

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• . Across the years, it was employed to prepare 2-hydroxypyrazines but some of its limits, notably regioselectivity issues when starting from α-ketoaldehydes, certainly hampered a full-fledged generation of pyrazine-containing new chemical entities of potential interest in medicinal chemistry. The present

• text describes some insights and improvements, such as the unprecedented use of tetraalkylammonium hydroxide, in the reaction parameters affecting the regioselectivity and yield when starting from phenylglyoxal and two α-aminoamides. We also suggest a mechanism explaining the counterintuitive

• expected 3,5-substituted-2-hydroxypyrazine isomer (3, R1 = H, R2 ≠ H) which is isolated sometimes along with a much smaller amount of the alternative 3,6-substituted-2-hydroxypyrazines (4, R1 = H, R2 ≠ H) [6][13][18][19][20][21][22][23][24][25][26][27][28]. This regioselectivity appears counterintuitive

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• functionalized spiro[cyclohexane-1,3'-indolines] in good yields and with good diastereoselectivity. On the other hand, the tri(n-butyl)phosphine-catalyzed reaction of 3-(ethoxycarbonylmethylene)oxindoles and bis-chalcones gave functionalized spiro[cyclohexane-1,3'-indolines] with different regioselectivity

• should be pointed out that the exocyclic benzylidene group exists on the C3-position in the newly formed cyclohexyl ring, while it exists on the C6-position in the above obtained spiro compounds 3a–z. This result clearly indicated that these two reactions have the opposite regioselectivity. Another kind

• of the zwitterion A to the isatylidene malononitrile 2 and 3-(ethoxycarbonylmethylene)oxindole 4 results in the different regioselectivity in the formation of the spiro compounds 3 and 5. For further demonstrate the synthetic value of this procedure, ethyl isatylidene cyanoacetates 6 were also

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

• alkynes to activate them for a decent yield of the isoxazole products, thus limiting the scope of the substrates in this method. In addition, this method requires high heat and produces very poor regioselectivity of the products [17][18]. The addition of copper catalysts in this route can help the

• reaction proceed at room temperature and improve both the regioselectivity and yields of the isoxazoles. However, these catalysts only work for the reaction with terminal alkynes and only produce 3,5-disubstituted isoxazole products (Figure 1) [19][20]. The synthesis of 3,4,5-trisubstituted isoxazoles from

• highly substituted non-terminal alkynes does not proceed with copper catalysts at room temperature. As an alternative, the usage of ruthenium(II) catalysts enables the reaction to proceed smoothly at room temperature and produces high yields and regioselectivity for both, 3,5-disubstituted and 3,4,5

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

• summarizing recent relevant literature reports. Keywords: annulation; cyclization; fused indoles; regioselectivity; SEAr; Introduction Over the decades, countless cyclization and annulation reactions of substituted arenes/heteroarenes involving an electrophilic aromatic substitution (SEAr) reaction as the

• published in the last decade [5][6][7], this is the first time the regioselectivity of the SEAr-based/terminated cyclization and annulation reactions of 3,5-unsubstituted, 4-substituted indolesis is sytematized as a dedicated topic. Discussion The Tsuji–Trost reaction serves as a powerful tool in

• regioselectivity in favor of the 4,5-fused indole system. Based on their experimental and computational investigations, the researchers hypothesized that Thorpe–Ingold effect could induce dispersive interactions between the indole and styrene moieties, triggering the preferential formation of the 3,4-fused indoles

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

• regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C–H bond, insertion of the olefin into the iridium

• hydride, and C–C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step. Keywords: C–H activation; density functional theory; hydroacylation; iridium catalysis; regioselectivity; Introduction Organic synthesis is

• , the regioselectivity of such reactions is still undefined (Scheme 1) [58]. While the chemistry of symmetric OBD derivatives is well established, their unsymmetrically substituted counterparts 5 have remained underexplored (Scheme 1). Upon C1-substitution, the reactivity of C1-substituted OBDs 5 can

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• inherent in the known triazolo[4,3-b][1,2,4,5]tetrazine system. However, their reactions have a low regioselectivity, thus leading to a large number of byproducts, thus making it difficult to separate the reaction mixture. All synthesized [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines 3–5 were screened in vitro

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

• using a silver-BINAP catalyst combination [25]. Later, the same group could successfully tune the catalytic system to control the regioselectivity in the addition of metal enolate to nitrosoarenes to achieve an α-hydroxyamination [26]. Since then, several groups have shown the use of metal-catalyzed

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• catalytic activity was demonstrated in promoting gold(I)-catalyzed cycloisomerization of 1,6-enynes, with ample scope and high regioselectivity. However, preliminary studies suggested that the catalytic event occurs outside the macrocyclic cavity. In order to get more insights on the role of the cavity to

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

• reusability of the recovered Lipozyme® TL IM was also checked and it was found that the lipase could be used up to seven cycles of selective acetylation of 3′-azido-3′-deoxy-β-ᴅ-allofuranosyl nucleosides 14a,b without noticeable loss of regioselectivity and efficiency. Thus, trihydroxy nucleosides 14a,b were

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

• cyclic β-amino acid derivative, was achieved by oxirane ring opening in epoxide 7 with HCl(g)–MeOH, NaHSO4, or NH4Cl–DMF. The regioselectivity of oxirane ring-opening in 7 was attributed to the conformational effects. The mechanism for the formation of compound 10 was elucidated with DFT computations

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• essential for promoting this reaction (Scheme 12). Both electron-rich and electron-deficient indoles afforded the desired products in good yields. The major advantages of this method include high regioselectivity, mild reaction conditions, and reusability of the catalyst. Two years later, in 2014, Ackermann

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

• heteroarenes were all well-tolerated; however, monosubstituted aryl rings suffered from low regioselectivity which is in accordance with HAS-type reactions [138]. In 2020, the Wu group expanded on the radical cyclization chemistry of γ,δ-unsaturated oxime esters, describing a carbonylative cyclization with

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

• (see Scheme 1C) [10]. Appropriately 2-functionalized quinazolinones of type 5 might be good starting materials for the intramolecular cyclization providing the target compounds (see Scheme 1D); however, this approach was rarely used [33][34][35][36], possibly due to low regioselectivity of the ring

• reaction proceeded with high regioselectivity as 5-exo-trig cyclization. The substituent in the quinazoline ring had virtually no effect at the yield or selectivity of the heterocyclization. Two pathways seem to be possible for the oxidative heterocyclization of quinazolinones 7 (see Scheme 2). The first

• )-ones was found. The reaction proceeds with high regioselectivity when 2.5 equivalents of PIFA are used in 2,2,2-trifluoroethanol solution at 0 °С over 24 h. The synthesized compounds represent a new class of functionalized pyrroloquinazolinones – close analogs of naturally occurring vasicinone

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

• substrates and the chiral phosphoric acid, with the substituent at the 1-position of the 2-naphthol playing a key role in controlling the regioselectivity [107]. Conclusion In recent decades, chiral phosphoric acids have been recognized as privileged chiral catalysts and ligands and have therefore become an

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• yields ranged 57–89% with ee 70–97% [52]. A similar chiral multifunctional thiourea/boronic acid was used as an organocatalyst by Michigami et al. for the enantioselective synthesis of N-hydroxyaspartic acid derivatives 76 with perfect regioselectivity and high enantioselectivity (Table 17) [53

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

• performed well in the reaction with 1,3-enynes 54, providing moderate yield and regioselectivity. The CuH-catalyzed intramolecular coupling of enyne containing a nitrile group worked smoothly and gave a moderate yield under standard conditions at a decreased concentration. A plausible mechanism according to

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• -5,6,7,8-tetrahydroacridine (4a) (Table 1, entries 1–6). Towards a better understanding of the regioselectivity of the coupling, we carried out a series of experiments with decreased amounts of phenylboronic acid. In all cases, the cross-coupling took place at both bromine atoms of 4a and we could never

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

• electrophilic addition (Scheme 26). Schwartz et al. developed a new route for the synthesis of exocyclic enol ether 83 and endocyclic enol ether 85 involving a Hg(II)-induced cyclization of acetylenic alcohols 82 and 84, respectively [79]. This work revealed that the regioselectivity of the Hg(II) addition to

• group (101), chromone derivatives 102 were formed. On the introduction of the methylene moiety in between the aryl and methoxy group, 103 yielded isofuran derivatives 104 due to the change in regioselectivity during the cyclization. Dihydronapthalenes 106 were synthesized by cyclization of the

A visible-light-induced, metal-free bis-arylation of 2,5-dichlorobenzoquinone

• Pieterjan Winant and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 2315–2320, doi:10.3762/bjoc.17.149

• multistep procedures requiring large amounts of toxic metal complexes [12][33][34]. Later improvements still demand prefunctionalization of the quinone substrate [35][36][37]. While effectively eliminating this requirement, CH bis-arylation using palladium complexes still suffers from regioselectivity

• combining photoredox and diazonium chemistry. By starting from the commercially available 2,5-dichlorobenzoquinone (1), we eliminate the issue of regioselectivity and effectively create a green synthesis pathway towards a versatile bis-electrophile. Results and Discussion We initiated our investigation by