Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• cost effective and selective, one-pot transformation. Pharmaceutical uses for bio-active cyclic molecules accessible by I(III) reagents are plentiful; anticancer drugs can be formed from the basis of pyrrolo[2,3-b]indoles 1 [3][4], 2-oxazolines 2 [5][6], dihydrofuran 3 [7][8], and spirocyclic scaffolds

• fluoride. Unsaturated alcohols gave moderate yields of racemic fluorinated tetrahydrofurans 26. Moderate yields were also reported for the fluorocyclisation of 3-butenoic acid (24) to form the fluorinated butyrolactone 28. The preparation of fluorinated oxazolines was reported in 2018 by Gilmour and co

• -workers (Scheme 16) [39]. p-TolIF2 is formed in situ from p-iodotoluene and Selectfluor in a 4.5:1 HF:amine solution, which is obtained by combining Et3N·3HF and pyridine·HF. A range of N-allyl carboxamides 31 were successfully cyclised forming fluoromethyl-2-oxazolines 32 in good yields. The synthesis of

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• their investigation of the hydrofunctionalization reaction of unsaturated amides and thioamides [28]. They have found that the oxygen atom of the amide group, rather than the nitrogen atom, acted as a nucleophile, leading to the formation of 2-oxazolines and 2-thiazolines. Another recent example of

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• -catalyzed cyclization of N-allylamides 1 and N-homoallylamides 2 to 2-oxazolines 4 and dihydrooxazines 5, respectively (Scheme 1A) [15]. We also reported that an N-bishomoallylamide 3 (n = 3) was cyclized under the reaction conditions, but in just 30% yield. It turned out that the product of this reaction

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• ) (Scheme 18). 17-Spiro-1,3-oxazoline steroids Jin et al. [37] described a series of spiro-1,3-oxazolines synthesized from the commercially available estrane derivative ethylene deltenone 24. This conjugated diene was regioselectively epoxidized at the 5(10) double bond to furnish compound 58

• . Amidoacetylenes 59 were synthesized after eight synthetic steps, and subsequently subjected to a copper(I)-catalysed cyclization to produce 17-spiro-1,3-oxazolines 60 in moderate to excellent yields (38–97%). The cyclization of acetamido and propionamido residues gave much better results than the use of formamido

• , albeit less potent than the reference drug. However, many oxazolines showed improved selectivity, with greater separation of antiprogestational and antiglucocorticoid activity (Scheme 19) [38]. 1,2-Aminoalcohols have been extensively utilized as building blocks for synthesizing spiro-1,3-oxazolidin-2

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• desired oxazoline products with reasonable yields (Figure 2, products 8–10). Heteroaromatic amides could also furnish the oxazolines 11 and 12 with good efficiency. Naphthaleneamide also generated the desired product 13, albeit with slightly lower efficiency. Interestingly, o- and m-methyl-substituted

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

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• polymerization process. Further work will be necessary to establish whether a living polymerization can be achieved by additional adjustments. Keywords: 2-alkyl-2-oxazolines; matrix-assisted laser desorption/ionization mass spectrometry; nuclear magnetic resonance; polymerization kinetics; Introduction

• hydrophilic polymers with a good safety and environmental profile has been a hot topic in recent years. Specifically, the search for more benign solvents for the polymerization of 2-alkyl-2-oxazolines has been ongoing for some time. Poly(2-oxazoline)s (POx) are a family of polymers investigated for a range of

• ]. Therefore, choosing environmentally benign solvents becomes ever more relevant [27]. Accordingly, some research groups have been also looking for "green" and safer solvents suitable for CROP of 2-oxazolines. "Green" solvents are considered environmentally friendly, less hazardous solvents that make a

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• highly efficient catalysts based on copper complexes of different types of chiral ligands, 2-(pyridin-2-yl)imidazolidine-4-ones (I–III), bis-oxazolines (IV–VII), or diamine (VIII) were chosen for the study (Figure 2). Furthermore, the modification of the structure of the prochiral aldehyde intermediates

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

• esters 1 and aziridines 2 (Scheme 2). Different 2-arylaziridines 2 were reacted with diazo ester 1a, affording oxazolines 3aa–ai in 60–91% yields. No obvious electronic effect was observed. Steric bulky 2-(2-chlorophenyl)aziridine (2f) gave the desired product 3af in the highest yield of 91%. Steric 2

• diazo esters 1 and aziridine 2i were performed, generating the corresponding oxazolines 3bi–gi in 73–94% yields. Ethyl 2-diazo-3-oxohept-6-enoate showed the highest activity, affording the desired product 3gi in 94% yield. One diazo amide, 2-diazo-N,N-dimethyl-3-oxobutanamide (1h), was tested with

• -oxoalkanoates are used in the reaction, showing specific chemoselectivities controlled by the electronic effect (Scheme 4). Conclusion A new and efficient synthetic method for the synthesis of oxazolines has been developed with alkyl 2-diazo-3-oxoalkanoates and 2-arylaziridines as starting materials. Alkyl 2

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

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

• (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

• [46]. Catalytic systems based on pyridine-oxazolines ligands Currently, the most studied ligand class is focused on pyridine-oxazolines (PyOx). The first report for the use of this type of ligand for the asymmetric addition of arylboronic acids to cyclic enones was published by the Stoltz group in

• not estimated after each cycle [58]. In 2019, Lee et al. focused on the enantioselective desymmetrisation of polycyclic cyclohexenediones [59]. The variously substituted pyridine-oxazolines L9 and L12a,b were tested as ligands in combination with Pd(OAc)2 or Pd(TFA)2 (Table 31). As a suitable solvent

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• expected products in good to excellent yields (Figure 37 and Figure 38). The addition of diphenylphosphoric acid as a ligand guaranteed higher yields and a broader reaction scope [100], including C–H activation substrates bearing alternative and modifiable DGs such as pyrazoles or oxazolines, as well as

• allowed a significant improvement of the reaction efficiency. The C–H coupling was compatible with a large panel of heteroaromatic substrates including benzoxazoles, oxazoles, thiazoles, and oxadiazoles, as well as non-aromatic oxazolines. Although the initial protocol necessitated the use of a

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• -exo-trig cyclization of the oxime radical followed by the addition of molecular oxygen to the formed C-centered radical with a formation of a peroxyl radical. The interaction of the latter with NO leads to the final oxynitro compound [131]. Cyano-substituted oxazolines 131 were synthesized from

• oxazolines in good yields (products 131a–e). Aliphatic oximes also enter this transformation, including an oxime containing a TBDPS protecting group (products 131f–h). The combination of AgSCF3 and catalytic amounts of Cu(OAc)2 was used for the synthesis of trifluoromethylthiolated isoxazolines 133 from

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• important role to promote this ring-opening N-alkylation, but also acts as an oxygen donor. Keywords: N-alkylation; oxazolines; potassium tert-butoxide; ring opening; thiazolidinones; Introduction 2-Oxazolines are important structural units in pharmaceutical applications and efficient ligands in

• coordination chemistry, and also valuable protecting or directing groups in catalysis [1][2][3]. 2-Oxazolines are a readily stable class of heterocycles resistant to a range of nucleophiles, bases, or radicals [4][5], which can be easily generated from amino alcohols and carboxylic acids, and from alkenes or

• epoxides as substrates via alternative synthetic procedures [6]. However, under acidic conditions, oxazolines transform into β-substituted carboxamides through nucleophilic ring opening with SN2 attack at the C5 position of the ring [7][8]. Recently, Guo’s group developed an efficient method for the

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• heterocycles [48][49][50][51][52][53][54], we developed a general method for the preparation of five- and six-membered cyclic iminoethers (2-oxazolines and 5,6-dihydro-4H-1,3-oxazines, respectively), by MW-assisted ring closure of amido alcohols promoted by PPA esters [54]. PPE and PPSE were then tested for

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• -aryl-2-iminoazacycloalkanes [84] and 2-oxazolines or their higher homologues [85], using polyphosphoric acid esters PPE (ethyl polyphosphate) [86] and PPSE (trimethylsilyl polyphosphate) [87] under microwave irradiation. PPE and PPSE are aprotic irreversible dehydrating agents of the Lewis acid-type

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• ][22]. This led us to extend the concept of spiro-fused carbohydrate oxazolines for asymmetric synthesis by developing new types of carbohydrate-based PHOX ligands. Herein, we present ten novel spiro-PHOX ligands containing diphenylphosphino groups, 5, which can be synthesized in four to six steps

• -fructose derivatives with different protective groups at position 3, 4 and 5 the hydroxy group of 6a was first protected to afford 6b. After removing the isopropylidene group, positions 4 and 5 of the resulting diol 7c were protected to afford 7d. A convenient method for constructing anomeric 2-oxazolines

• is hindered. In the literature this fact is used to explain the different reactivities between “armed” and “disarmed” glycosyl donors in glycosylation reactions [33]. Due to the fact that 9 can be attacked from two sides by nitriles, the oxazolines occur in two isomeric forms, the β-anomers (10) and

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• ). The reaction uses 2H-azirines and aldehydes to access the functionalised heterocycles [61]. Unlike the pyrrole-forming reaction, this protocol requires an oxidising agent, DDQ, for the desired oxazole to be obtained. This means that access to the corresponding 2,5-oxazolines is also possible

• , scalable and environmentally friendly reaction conditions than the traditional methods employed for making these highly substituted heteroaromatics. Access to the saturated oxazolines and thaziolines from amides and thioamides, respectively, has been described by Nicewicz who used acridinium salt

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• available. This led to the selection of naphthyridine, pyridazine, pyrazole, and phenol building blocks. We opted to connect these linkers to oxazolines via amide bonds. The reasoning for this was twofold. Firstly, this should provide ligands with significantly improved stabilities over for instance imine

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• result was obtained by replacing PhI(OAc)2 with PhI. In addition, phosphates were suitable nucleophiles in this reaction, giving phosphoryloxylactones in good yields [44]. A similar catalytic cyclization of unsaturated amides leading to oxazolines and dihydrooxazines was developed, in which Selectfluor

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

•  20. In 2016, Zhang and Yang reported an asymmetric palladium-catalyzed addition of arylboronic acids 60 to sterically hindered N-tert-butylsulfonylisatin imines 61 [80]. Among a variety of chiral ligands investigated, including different pyridine-oxazolines, oxazolines and (R)-BINAP, the chiral

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the

• ; cyclisation; fluorination; gauche effect; hypervalent iodine; oxazolines; Introduction Marine and terrestrial natural product bioprospecting has established a broad spectrum of structurally complex, bioactive metabolites containing the venerable 2-oxazoline unit [1][2]. This diversity is exemplified by the

• methods. To contribute to the current catalysis ordnance for the preparation of 2-oxazolines, and provide a direct route to 5-fluoromethyl derivatives from simple unactivated alkenes, the fluorocyclisation of N-allylcarboxamides facilitated by the in situ generation of p-TolIF2 was envisaged [8][9][10][11

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• Antony J. Fairbanks Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, 8140, New Zealand Biomolecular Interaction Centre, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand 10.3762/bjoc.14.30 Abstract N-Glycan oxazolines have found

• subsequently relied on the Lewis acid catalysed conversion of peracetylated N-glycan oligosaccharides produced in this manner into their corresponding oxazolines, followed by global deprotection. However, a key breakthrough in the field has been the development by Shoda of 2-chloro-1,3-dimethylimidazolinium

• these materials, in concert with DMC-mediated oxazoline formation as a final step, allow access to a selection of N-glycan oxazoline structures both in larger quantities and in a more expedient fashion than is achievable by total synthesis. Keywords: DMC, ENGase; glycosyl oxazolines; N-glycans

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• alkenes leading to oxazolines 37 was described by Fu and co-workers in 2014 [37]. In this work iodobenzene diacetate (PIDA) was used as the oxidant to generate the CF3 radical from CF3SO2Na (Scheme 18). Hydrotrifluoromethylation of alkenes: Direct alkene hydrotrifluoromethylation by means of CF3SO2K under