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

• -stereocontrolled ring-opening reactions of oxa- and azabicyclic olefins with dialkylzinc reagents catalyzed by a nickel compound (Scheme 1) [60]. The reaction was entirely stereoselective; however, unsymmetrical OBDs 5 produced mixtures of regioisomers 6 and 7. In the same year, Hill and co-workers published a

• 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

• (EDGs) led to naphthol compounds 9, while electron-withdrawing groups (EWGs) led to the anticipated ring-opened 1,1,2-trisubstituted naphthalene framework 10 [61]. On the other hand, Edmunds and co-workers described a ring-opening reaction of C1-substituted OBDs 5 with arylboronic acids that was

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

• occur followed by ring-opening and ring closure (Scheme 4). It has been found that triazolo[1,5-b][1,2,4,5]tetrazines 3 do not enter the characteristic for isomeric [4,3-b]-annulated derivative reactions with malonic ester, leading to expansion of the tetrazine ring and the formation of

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

• -functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8

• material in the synthesis of the other isomer of β-amino acid 6. The ring-opening reaction of 7 with HCl(g) in MeOH resulted in a mixture of products 8 and 9 in a 9:1 ratio (1H NMR). The product 8 in the reaction mixture was purified by recrystallization from ethanol/ether, but all attempts to purify the

• the epoxide-ring-opening reaction of 7 with sodium azide, to introduce an extra amino group in position 4 on the cyclooctane skeleton. For this, epoxide 7 was treated with NaN3 in the presence of NH4Cl/DMF and this formed lactone 13 as the sole product in 80% yield (Scheme 4). The epoxide 7 was

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• in the presence of electrophilic reagents [18][19] (Scheme 1d). Aziridines can be considered as the NCC structural fragment after ring-opening and have been applied in the synthesis of aziridine-imine-containing chiral tridentate ligands [20], 2-alkylideneoxazolidines [21], and N-vinylamides [22]. We

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• conditions. In sharp contrast, the corresponding six-membered α-bromo-δ-valerolactone has a more-distorted ring and is extremely unstable, even at room temperature [39][40][41]. In fact, it must be stored in a freezer because ring-opening polymerization and ring-contraction reactions occur readily at room

• –Volhard–Zelinsky-type ring-opening reaction of 1a (Table 1). In this reaction, the corresponding acid bromide is formed in situ by heating with Br2 and a substoichiometric amount of PBr3; the acid bromide is then converted into 2,5-dibromopentanoic acid (2a) via hydrolysis during the workup under open-air

• -ECX400 (100 MHz) FT NMR or JEOL JNM-ECS400 (100 MHz) FT NMR system in CDCl3. Ring-opening reaction of δ-valerolactone (1a) with Br2 in the presence of a catalytic amount of PBr3 (entry 1, Table 1). To a 50 mL three-neck flask were added δ-valerolactone (1a, 5 mmol) and PBr3 (5 mol %), then Br2 (1.0 equiv

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

• byproducts were detected which supports the absence of an initial oxidative addition between the alkyl iodide and the active Fe catalyst. The possibility of a radical process rather than ionic cross-coupling is supported by the tandem cyclization/cyclopropyl ring-opening reaction, similar to previous reports

• sterically hindered tertiary alkyl bromides, the authors were able to favor intermolecular radical addition of the generated alkyl radical 17 to the vinylcyclopropane, outcompeting radical rebound to an aryl Fe species. The incipient radical can then undergo ring-opening of the cyclopropane 18. Work by

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

• of them (pathway a) includes the formation of the nitrene cation 11 [41][42][44][45][53] under action of PIFA as an oxidant. A subsequent electrophilic attack at the double bond provides aziridinium cation 12 that undergoes selective ring opening with the trifluoroacetate anion to give intermediate

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

• be prepared by substrate-directed epoxidation. A subsequent SN2 intramolecular epoxide ring-opening cyclization could provide an N-Cbz-protected pyrrolidine derivative with a hydroxymethyl group at C-5 and with trans configuration relative to the hydroxy group at C-4. Finally, (±)-codonopsinol B (1

• terminal alkenes bearing both an allylic and homoallylic-type hydroxy group, yielding a sole threo isomer, are rare [36]. The cyclization of 5 through an epoxide ring-opening reaction with boron trifluoride etherate in dichloromethane at 0 °C yielded pyrrolidine derivative 12 in 69% isolated yield [37

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

• hydrogen bonding, and the azalactones underwent asymmetric ring opening to form axially chiral oxindole-based styrenes 85 in up to 53% yield with good diastereoselectivities (up to 94:6 dr) and enatioselectivities (up to 95% ee). Moreover, the racemic oxindole-based styrenes underwent kinetic resolution to

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• α-lithio ethers, to give convergent access to allylic alcohols and allylic amines, respectively. The process can be considered as proceeding by selective strain-relieving attack (ring-opening) of the lithiated three-membered heterocycle by the lithio ether and then selective β-elimination of lithium

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• halide anions can also engage as the nucleophile, which has been exploited in ring opening and related reactions (Figure 3b). In general, the idea of enantioselective ring opening produces two fixed stereocenters during one synthetic operation, increasing the complexity of the product significantly. This

• makes asymmetric ring-opening reactions a powerful tool for the synthesis of highly complex target molecules. With this concept in mind, anion-binding catalysis has successfully been employed for asymmetric ring-opening reactions, implying halide anions as both mere counter-anions in the ion-pair

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• continuous development and improvement of polymerization techniques, more and more diverse copolymers can be synthesized. Very recently, Kertsomboon et al. succeeded in preparing a copolymer (poly(AAm-co-MDO)) of acrylamide and a degradable, hydrophobic monomer based on a ring opening polymerisation of

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

• opening attempt of chiral oxirane 153 in the presence of BF3.Et2O (Scheme 20) [104]. The synthetic route to the desired product was smoothly brought to its course by employing CuCN in the medium. Amines The enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are responsible

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

• Abstract This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with

• ; organofluorine chemistry; selectivity; Introduction Olefin metathesis is considered to be a powerful synthetic tool for the creation of olefin bonds [1]. Several types of metathesis reactions, such as ring-opening metathesis (ROM), cross-metathesis (CM), ring-closing metathesis (RCM) or ring-opening/cross

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• enzymes cannot distinguish between acceptors with different lengths in the reaction mixture. Chemical polymerization is often performed by ring-opening of the respective anhydrosugar (Figure 1B) or polycondensation reactions. This approach is highly valuable to generate long chains in short time, allowing

• access a broader scope of cellulose modifications, chemical polymerization is a more suitable option. Ring-opening polymerization (ROP) of orthoesters 4 (Scheme 1B) is an established procedure for the synthesis of β(1–4)-glucopyranan structures. The first chemical synthesis of stereoregular cellulose was

• control over size and substitution pattern. Classical methods include chitinase-catalyzed assembly via ring-opening polyaddition of N,N’-diacetylchitobiose oxazoline derivatives [237][238][239] or self-condensation of N-phthalimide protected thioglycoside [240]. Enzymatic polymerization promoted by

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• action of Meerwein’s salt (Me3OBF4) and a mild base (proton sponge) to afford a methoxy cedrene derivative. Next, oxidative cleavage of the double bond using NaIO4/RuCl3·xH2O enabled a ring opening, followed by lactonization promoted by CuBr2 via an intramolecular acyloxylation. The 5,5-fused ring system

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• of the imine intermediate produces the intermediate enamine 13. The 1,3-dipolar cycloaddition of enamine 13 with azide produces intermediate 1,2,3-triazoline 14. In continuation, a ring-opening process is promoted by acetic acid to afford the intermediate 16. Afterward, triazene intermediate 17 was

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ′-ketonucloside 1 with trimethylsulfoxonium iodide in DMSO afforded the spironucleoside 2, which in turn was converted to the TIPDS-protected 2′-(pyrimidin-1-yl)methyl-/2′-(purin-9-yl)methylarabinofuranosyluracil derivatives 3a–f by nucleophilic epoxide ring opening with thymine, N-benzoyladenine, 6-O-allyl-N

• ]. Nielsen and co-workers [42] additionally synthesized 2′-(N-benzoylcytosin-1-yl)methylarabinofuranosyl-N-benzoylcytosine (7) from uridine using a similar methodology. Thus, the nucleophilic epoxide ring opening in spironucleoside 2 with uracil in DMF in a N1-regioselective manner afforded the TIPDS

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• thioglycosides prepared from deoxyfluorinated 1,6-anhydro-2-azido-β-ᴅ-hexopyranose precursors by ring-opening reaction with phenyl trimethylsilyl sulfide. Nucleophilic deoxyfluorination at C4 and C6 by reaction with DAST, thioglycoside hydrolysis and azide/acetamide transformation completed the synthesis

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

• enantioselectivities were low to moderate (up to 60% ee; Table 34) [14]. Another option to obtain the linear product is the ring opening of the addition product of the arylboronic acid to the dihydropyran-2-one derivative (Scheme 23) [14]. The Minnaard group next focused on the increase of the reactivity of ortho

• arylboronic acids [59]. Attempt to use the catalytic system L2/Pd(TFA)2 for the addition of phenylboronic acid to 3-methyl-2-cyclohexenone [14]. Ring opening of an enantioenriched tetrahydropyran-2-one derivative as alternative strategy to linear products [14]. Synthesis of biologically active compounds from

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

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

• gave the desired THP as a 14:1 mixture of trans- and cis-265 in 80% yield. The trans-265 was obtained as a major isomer, where the reaction proceeded through the 6-membered chair-like transition state 264, and the electrophilic ring opening of cyclopropane by the oxocarbenium ion was believed to

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

• product is then reacted with unprotected thymine which, in the presence of stoichiometric amounts of sodium hydride, results in the epoxide ring opening and the formation of the glycol backbone. The pre-amidite is then phosphitylated yielding the desired GNA-T amidite (Scheme 3). Recently, this simple