An initiator- and catalyst-free hydrogel coating process for 3D printed medical-grade poly(ε-caprolactone)

• Jochen Löblein,
• Thomas Lorson,
• Miriam Komma,
• Tobias Kielholz,
• Maike Windbergs,
• Paul D. Dalton and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2021, 17, 2095–2101, doi:10.3762/bjoc.17.136

• non-conductive polymers like water-soluble poly(2-ethyl-2-oxazoline) (PEtOx) [35], polypropylene (PP) [36][37] photo-cross-linkable and biodegradable poly(ʟ-lactide-co-ε-caprolactone-co-acryloyl carbonate) [38], or thermoplastic elastomers [39] have successfully been processed via MEW [40

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

• 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

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• olefins 84 as nucleophile partners and racemic secondary and tertiary α-bromo-N-protected β-lactams 83 under nickel catalysis, along with the chiral bis(oxazoline) ligand 85 and triethoxysilane (Scheme 32) [108]. Substrate structural variations on 84 had only a small impact on the reaction

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• was further demonstrated by a series of successful derivatizations of the cyano-substituted oxindole 8a. For instance, after the Ritter reaction, 8a was smoothly converted to N-tert-butylated acetamide 12 in 96% yield (Scheme 6b). A modified Witte–Seeliger reaction led to the formation of oxazoline 13

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

• catalytic cycle as outlined in Scheme 21 [59]. The latest ligand derived from pyridine-oxazolines is β-carbolino-oxazoline, whose Pd(II) complex was studied mainly as a catalyst for the addition of arylboronic acids to nitrostyrenes. It also showed to be a highly active catalyst for the addition to enones

• substrates as well as for 2-unsubstituted chromones [17][18][19][21][22][23][24]. On the other hand, there is only one example of the usage of a rhodium-based catalyst for the addition of arylboronic acid to 3-substituted enones. The olefino-oxazoline ligand L18 has been used for the rhodium-catalysed

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• -position of an oxazoline or amide is selectively activated using a copper or palladium catalyst. Manganese is one of the most abundant and nontoxic transition metals found in the earth’s crust and its corresponding complexes and salts are useful in synthetic organic reactions [29][30][31][32][33][34][35

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• . Condensation with 2-amino-2-methylpropan-1-ol and oxidation with NBS yielded oxazoline 6 in a good yield. Directed ortho-metalation utilizing TMPMgCl·LiCl under mild conditions and subsequent smooth formylation with DMF afforded benzaldehyde 7 (see Scheme 2). Due to rapid decomposition of 7 under ambient and

• diphenylphosphoryl azide (DPPA) in excellent yield. Finally, the oxazoline group, which acted as directing and protecting group, was removed in a three-step sequence of N-methylation, reduction of the in situ formed iminium ion and acidic hydrolysis. This afforded the azide-functionalized para-bromobenzaldehyde 3 in

• 78% yield and an overall yield of 56% (starting from 4-bromobenzaldehyde). Azide-functionalized ortho-bromobenzaldehyde 4 was prepared by a similar route as aldehyde 3. Initially, oxazoline formation from 4-methylbenzaldehyde yielded 2-aryloxazoline 10 in almost quantitative yield. The introduction

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

• unsaturated oximes 130 using a combination of t-BuONO and a ruthenium catalyst (Scheme 43) [132]. The authors proposed that the interaction of unsaturated oxime with TBN produced a hydroxyiminomethylisoxazoline (Scheme 40) [130] that was transformed into the cyano-substituted oxazoline in the presence of a

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

• Qiao Lin Shiling Zhang Bin Li School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, Guangdong Province, P.R. China 10.3762/bjoc.16.44 Abstract An efficient and simple KOt-Bu-promoted selective ring-opening N-alkylation of 2-methyl-2-oxazoline or 2-(methylthio)-4,5

• -substituted thiazolidinone derivatives under mild conditions (Scheme 1c). Results and Discussion To test this ring-opening N-alkylation of 2-oxazoline, benzyl bromide (1a) and 2-methyl-2-oxazoline (2) were chosen as the model substrates for the reaction in the presence of 20 mol % of CuBr2, 2 equiv of KOt-Bu

• 70–85% yield, respectively. Notably, the steric and inductive effects of the substituents did not hamper this ring-opening N-alkylation. Allyl bromide (1h) successfully reacted with 2-methyl-2-oxazoline and produced the corresponding product 3h in good yield (69%). More importantly, bromide

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• was obtained by the reaction of ʟ-valinol with in situ-generated indolylacyl chloride. The latter compound was obtained through an oxalic acid-mediated chlorination of carboxylic acid 96 with dimethylformamide as catalyst in dichloromethane. Next, oxazoline derivative 98 was obtained via a

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• methodologies need, e.g., an ester, orthoester or oxazoline protecting group for the acid. But also the tert-butyl ester-functionalized boroxine 25 is suitable for the cross coupling. With the current catalytic system, coupling of 2-substituted boroxines (26, 27) remains challenging, but optimizing the

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• formation of (1S,2S)-49 and provided a basis for the inversion of configuration at C2 by O-mesylation and intramolecular displacement to yield the 2-oxazoline (4S,5R)-54 readily hydrolyzed to florfenicol ((1R,2S)-49). Naturally occurring tyroscherin ((2S,3R,6E,8R,10R)-55) was recognized for its anticancer

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• library of aldehydes (aromatic: 97–99% ee; aliphatic: 84–98% ee) [28]. Thereafter, many different kinds of hydrogen bonding-based organocatalysts have been developed for oxo-DA reactions [29][30][31][32][33][34][35]. One kind of organocatalyst in particular, which is based on an oxazoline template with

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• in Scheme 5, the oxazole-bearing α-amino ester 43 was prepared from the aspartic acid derivative 37 through the propargylamide 38 followed by a gold(I)-catalyzed cyclization to form the oxazoline derivative 40. Concerning the amidation step, propargylamide 38 was obtained in 78% yield provided that

• amount of gold(I) in warm toluene provided us with the oxazoline 40 in an 80% yield. However, this compound turned out to be unstable, either on standing, probably because of an autoxidation, as reported in other instances [27], or in CDCl3, probably because of acid traces. To achieve its isomerization

• chemistry aiming at the preparation of oxazole-bearing α-amino esters which was of interest per se. Indeed, the previously unreported acid-catalyzed conditions to achieve the isomerization of the methylene-bearing oxazoline 40 into oxazole 41 should be useful in many other instances. In any case, as

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

• ligands are prepared in two steps from readily available 1,2-O-isopropylidene protected β-D-fructopyranoses by the BF3·OEt2-promoted Ritter reaction with 2-bromobenzonitrile to construct the oxazoline moiety followed by Ullmann coupling of the resulting aryl bromides with diphenylphosphine. Both steps

• acetate as model substrate. Keywords: Fürst–Plattner rule; oxazoline; Ritter reaction; Tsuji–Trost reaction; Ullmann coupling; Introduction The vast majority of biologically active compounds like vitamins and natural products occur as single enantiomers in nature. Usually only one enantiomer generates

• -glucosamine and the sugar was linked to the aromatic system via an annulated oxazoline. Palladium complexes of 2 were used in allylic substitution of allyl acetates with dimethyl malonate as nucleophile and ee values from 69% to 98% were obtained [19]. Recently, we presented the synthesis of carbohydrate

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

• to form a five-membered metallacycle, subtending N(2)–Ni(1)–N(3) and N(5)–Ni(2)–N(6) angles of 81.53° and 80.34°, respectively. Additionally, the nitrogen atoms on the oxazoline and amide moieties form six-membered rings with the nickel(ΙΙ) center with N(1)–Ni(1)–N(2) and N(4)–Ni(2)–N(5) angles of

• backbone of complex 16·Ni2(OAc)2 shows a helical arrangement. This helicity is facilitated by the innate stereogenic centers of the oxazoline moieties which is further extended by the flexibility afforded by the amide connections. Naphthyridine ligand 22-H2 was designed as an analogue of ligand 16-H2 that

• an acetate anion. The nitrogen atoms from pyrazole and amide moieties coordinate to the two nickel centers to form five-membered metallacycles, subtending N(1)–Ni(1)–N(2) and N(4)–Ni(2)–N(5) angles of 84.0° and 85.0°, respectively. Similarly, the nitrogen atoms on amide and oxazoline moieties form

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• of tyrosine derivatives to spirolactams using iodine(III) reagents. In this reaction, oxazoline derivatives 41 were cyclized to spirocyclic products 42 using PIDA (15) as an electrophile in trifluoroethanol at room temperature for 30 minutes. The desired products 42 were isolated in moderate yields

• (Scheme 12). Additionally, the same research group [81] reported the oxidative cyclization of a phenolic substrate to a spirolactam using PIDA as electrophile. In this methodology, oxazoline 43 was cyclized to spirolactam 44 in 50% yield using PIDA (15) in trifluoroethanol at room temperature (Scheme 13

• same research group [104]. In this report, spirocyclic oxazoline 93 was prepared by starting from para-substituted phenolic compound 92 under the reaction conditions mentioned in Scheme 32 (Scheme 33). In 2002, Honda and co-workers [105] reported the synthesis of naturally occurring (−)-TAN1251A (95

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• in the order of the oxazoline ring formation and the aryl transfer steps. In our model transformation, it was found that the reaction generally features the aryl transfer–ring closing sequence and this sequence shows very limited sensitivity to the variation of the substituent of the reactants. On

• the basis of the mechanism the origin of the stereoselectivity is ascribed to the interaction of the Cu ion with the oxazoline oxygen driving the ring-closure step selectively. Keywords: catalysis; DFT calculation; iodonium salts; reaction mechanism; tandem arylation–cyclisation; Introduction

• before the C–O bond formation in the ring closing step (see Scheme 1). As an example of the catalytic arylation–cyclisation strategy, an efficient procedure to form substituted oxazoline derivatives from alkyl and aryl propargylamides has been developed. The process involves a 5-exo-dig cyclisation and

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• selectivity was the chiral oxazoline unit and not the inherent chirality of calixarene skeleton. Asymmetric hydrogenation Starting with distally O-dialkylated calixarene precursors, a series of BINOL-derived calix[4]arene-diphosphite ligands 40a–g were synthesized by Liu and Sandoval through phosphorylation

• achieve reusable catalysts for batch and continuous-flow studies. Inherently chiral calix[4]arene-based phase-transfer catalysts. Calix[4]arene-amides used as phase-transfer catalysts. Proposed transition state model of asymmetric Henry reaction. Structure of inherently chiral oxazoline calix[4]arenes

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

• pyridine-oxazoline ligand In-Pyrox was found optimal to provide a wide variety of chiral 3-amino-2-oxindoles 62 in moderate to high yields (51–97%) and uniformly excellent enantioselectivities (91–98% ee). As shown in Scheme 21, the reaction performed at 70 °C in TFE as solvent proceeded well in the

• enantioselectivities (up to 94% ee) by using chiral nickel and palladium complexes with imidazoline and pyridine-oxazoline ligands while the first additions of enaminones to isatin imines catalyzed by chiral phosphoric acids provided even higher enantioselectivities (up to 97% ee). In spite of these significant

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• spirocyclization of naphthol carboxylic acid [34]. Later Birman et al. reported a new variation of a chiral I(V) reagent, namely 2-(o-iodoxyphenyl)oxazoline derivative 28 [35]. The reagent was applied to an asymmetric [4 + 2] Diels–Alder dimerization of phenolic derivatives 29 to construct tricyclic derivatives 30

• with moderate enantioselectivity (Scheme 4). Although modest ees were obtained, this chiral oxazoline-based compound demonstrated encouraging potential as a new class of chiral hypervalent iodine reagent. Fujita et al. synthesized non C2-symmetric chiral iodoarene reagents 9a derived from lactic acid

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

• -ray crystallographic analysis of a representative example. Given the importance of fluorine in drug discovery, its ability to modulate conformation, and the prevalence of the 2-oxazoline scaffold in Nature, this strategy provides a rapid entry into an important bioisostere class. Keywords: catalysis

• ; 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

• siderophore antibiotic D-fluviabactin, the cytotoxic agent westiellamide, the antifungal macrodiolide leupyrrin A1 and the antitumour compound BE-70016 (Figure 1). In addition, synthetic polymers based on the 2-oxazoline building block constitute versatile platforms for a range of biomedical applications

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• synthesis of dendrimers and their applications as nanoreactors and catalyst carriers have been extensively studied over the last decades [94][95][96]. Fan and co-workers incorporated a bis(oxazoline)-copper(II) complex in the hydrophobic core of a polyether dendrimer [11]. The copper catalytic complex was