Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• , highlighting both the accomplishments and the future work needed in this important area. Throughout the discussion below, it is clear that there are privileged ligand architectures of these copper-catalyzed alkynylations. High enantioselectivities have been achieved with pyridine bis(oxazoline) (Pybox), bis

• (oxazoline) (Box), and Quinap-type ligands (Figure 1). Review Additions to iminium ions Although this review will focus on enantioselective additions to cyclic electrophiles, it is worth noting that the first enantioselective additions of chiral copper acetylides to imines or iminium ions utilized acyclic

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• of trans-4,5,9,10-tetrahydroxy-9,10-dihydrophenanthrene at room temperature (Scheme 4). In 1994, Meyers and Nelson [23][24] developed a copper-mediated asymmetric biaryl coupling with oxazoline as the chiral auxiliary to afford the biaryl-coupling products in high diastereomeric purity (dr = 93:7

• )hexopyranose derivatives. Preparation of 3,3’-disubstituted MeO-BIPHEP derivatives. Enantioselective synthesis of trans-4,5,9,10-tetrahydroxy-9,10-dihydrophenanthrene. Copper-catalyzed coupling of oxazoline-substituted aromatics to afford biaryl products with high diastereomeric purity. Total synthesis of O

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• Madhuri Vangala Ganesh P. Shinde Department of Chemistry, Indian Institute of Science Education and Research, Pune 411 008, India 10.3762/bjoc.11.249 Abstract The TMSOTf-mediated synthesis of β-configured spirocyclic 2-substituted-2-oxazoline ribosides was achieved using a “Ritter-like” reaction

• spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group. Keywords: fructose; oxazoline; riboside; Ritter reaction; spiro; Introduction 2-Oxazolines represent a unique class of 5-membered heterocyclic

• compounds with a wide range of applications spanning different chemistry disciplines. 2-Oxazoline derivatives are extensively studied due to their presence in numerous bioactive natural products [1][2][3] and synthetic drugs with anticancer, antibiotic, antidiabetic, and antifungal properties (Figure 1, 1–4

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• or secondary sulfonamides 15 with the assistance of 1,10-phenanthroline as a ligand (Scheme 3). Notably, the asymmetric version of a similar amidation had been previously achieved by Clark et al. via copper catalysis in the presence of a chiral oxazoline ligand, which allowed the synthesis of

• alkene substrates were systematically investigated by Chemler and co-workers. For example, they [67] developed the copper-catalyzed protocol for the sulfonamidation reaction of alkenes 68 via direct C–H activation to provide N-vinylsufonamides 69 in the presence of an oxazoline ligand. On the other hand

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• , heteroaryl, and alkyl, etc. to produce α,β-unsaturated acylimidazolidinones 215. Next, the Evan’s asymmetric DA methodology involving a [4 + 2] cycloaddition of chiral bis(oxazoline) in the presence of Cu(OTf)2 was employed to furnish the required norbornene system 216. Later, it was converted into a lactam

Synthesis of racemic and chiral BEDT-TTF derivatives possessing hydroxy groups and their achiral and chiral charge transfer complexes

• Sara J. Krivickas,
• Chiho Hashimoto,
• Junya Yoshida,
• Akira Ueda,
• Kazuyuki Takahashi,
• John D. Wallis and
• Hatsumi Mori

Beilstein J. Org. Chem. 2015, 11, 1561–1569, doi:10.3762/bjoc.11.172

• -TTF (2), TTF (3), BEDT-TTF (4), EDT-TTF-methyl-oxazoline 5, and trans-dimethyl-EDT-TTF (6). (a) Crystal structure, (b) θ21-type donor arrangement of molecules A and A’ [(S,S) and (R,R)-2 indicated by red and blue with charge of +0.59(8)], B and B’ [(R,R) and (S,S)-2, blue and red with +0.23(7)], and C

New palladium–oxazoline complexes: Synthesis and evaluation of the optical properties and the catalytic power during the oxidation of textile dyes

• Rym Hassani,
• Mahjoub Jabli,
• Yakdhane Kacem,
• Jérôme Marrot,
• Damien Prim and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2015, 11, 1175–1186, doi:10.3762/bjoc.11.132

• University of Versailles Saint-Quentin-en-Yvelines, Institut Lavoisier de Versailles, UMR CNRS 8180, 45, avenue des Etats-Unis, 78035 Versailles, France 10.3762/bjoc.11.132 Abstract The present paper describes the synthesis of new palladium–oxazoline complexes in one step with good to high yields (68–95

• used for the total synthesis of natural products and nanocompounds [5]. It is only since 1986 that oxazoline-based ligands have been utilized in asymmetric catalysis. This initiated considerable research activity in this field and triggered the synthesis of numerous chiral ligands containing at least

• one oxazoline ring [6]. Oxazoline units are expected to readily coordinate to a metal center and have been shown to bind a wide range of transition metals [7]. The wide variety of ligands with one or more oxazoline rings incorporating different heteroatoms, additional chiral groups, and specific

Regioselective synthesis of chiral dimethyl-bis(ethylenedithio)tetrathiafulvalene sulfones

• Flavia Pop and
• Narcis Avarvari

Beilstein J. Org. Chem. 2015, 11, 1105–1111, doi:10.3762/bjoc.11.124

• ethylenedithiotetrathiafulvalene-oxazoline (EDT-TTF-Ox) donors [5][6], due to a structural disorder effect [7]. Evidence was thus provided, and confirmed later on with a second complete series of conducting salts based on the same donors [8], that the presence of chiral centers can modulate the structural disorder of radical

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• and co-workers developed various N-sulfinyl homoallylic amines (76) [160] and N-cinnamyl sulfonamides (77) [161] ligands for the rhodium-catalyzed asymmetric 1,4-arylation of a variety of α,β-unsaturated carbonyl compounds. Finally, in 2012, Franzén and co-workers designed an indole-olefin-oxazoline

• either a Sc(OTf)3–3,3′-bis(diethylaminomethyl)-1,1′-bi-2-naphthol complex (85) or Cu(OTf)2–(S,S)-2,2′-isopropylidene-bis(4-tert-butyl-2-oxazoline) complex (86) (Figure 6). The latter bis(oxazoline) and its derivatives have become common chiral ligands in Lewis acid-mediated reactions [179]. The Evans

• group has developed several methods for Diels–Alder and aldol reactions that employed chiral bis(oxazoline) copper(II) complexes [180]. Starting in 1999, Evans and co-workers published a series of papers which reported the Mukaiyama–Michael addition to various α,β-unsaturated Michael acceptors [181][182

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• Simon A. Herbert Laura J. van Laeren Dominic C. Castell Gareth E. Arnott Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa 10.3762/bjoc.10.291 Abstract The diastereoselective oxazoline-directed lithiation of calix[4]arenes is

• reported with diastereoselective ratios of greater than 100:1 in some instances. Notably, it has been found that the opposite diastereomer can be accessed via this approach merely through the choice of an alkyllithium reagent. The inherently chiral oxazoline calix[4]arenes have also been preliminarily

• examined as ligands in the palladium-catalyzed Tsuji–Trost allylation reaction, returning results comparable to their planar chiral ferrocene counterparts pointing towards future application of these types of compounds. Keywords: calix[4]arene; inherently chiral; ortholithiation; oxazoline; Tsuji–Trost

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• the van Leusen reaction from trans-3-(2-vinylphenyl)acrylaldehyde which is prepared from o-vinylbenzaldehyde and (formylmethylene)triphenylphosphorane. The 4- and 5-(2-vinylstyryl)oxazoles afford, by photochemical intramolecular cycloaddition, diverse fused oxazoline-benzobicyclo[3.2.1]octadienes

• , which are identified and characterized by spectroscopic methods. The photoproducts formed are relatively unstable and spontaneously or on silica gel undergo oxazoline ring opening followed by formation of formiato- or formamido-benzobicyclo[3.2.1]octenone derivatives. On irradiation of 4-(2-vinylstyryl

• intramolecular photocycloaddition to diverse fused tetracyclic oxazoline compounds which further spontaneously or during the work-up procedure hydrolyze to benzobicyclo[3.2.1]octenone derivatives. This is a new method for the synthesis of functionalized benzobicyclo[3.2.1]octenes. Results and Discussion cis

Rational design of cyclopropane-based chiral PHOX ligands for intermolecular asymmetric Heck reaction

• Marina Rubina,
• William M. Sherrill,
• Alexey Yu. Barkov and
• Michael Rubin

Beilstein J. Org. Chem. 2014, 10, 1536–1548, doi:10.3762/bjoc.10.158

• Abstract A novel class of chiral phosphanyl-oxazoline (PHOX) ligands with a conformationally rigid cyclopropyl backbone was synthesized and tested in the intermolecular asymmetric Heck reaction. Mechanistic modelling and crystallographic studies were used to predict the optimal ligand structure and helped

• regio- and enantioselectivities. On the other hand, superior results were obtained using chiral ligands of the P,N-type [15][41][42][43][44]. Particularly, excellent enantioselectivities were achieved using different variations of phosphanyl-oxazoline (PHOX) ligands [45][46][47][48][49][50][51][52

• substrates [59]. A highly efficient asymmetric arylation in the presence of sugar-derived phosphite-oxazoline ligands was reported by Diéguez and Pàmies [47][48]. PHOX ligands are very appealing due to their high catalytic potential and modular design, which permits easy preparation of a series of analogues

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• attached to the anomeric center of the glucosamine moiety using oxazoline 6 [37][38][39]. Deacetylation and subsequent installation of the benzylidene protective group then gave alcohol 9. Coupling of 9 with (S)-2-chloropropanoic acid in the presence of sodium hydride resulted in the formation of protected

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• branched monosubstituted allyl acetate favoring the branched products. However, linear products were favored when the linear allyl substrates were employed [23][24]. The chiral oxazoline–phosphite ligands introduced by Pfaltz and coworkers proved to be highly efficient for regio- and enantiocontrol in the

• an elegant synthesis of bis(perfluoroalkyl)phosphine-oxazoline ligands where small but strongly electron-withdrawing substituents were introduced at the phosphorus [34]. 1,2-Ferrocene based P,N-ligands were synthesized and gave excellent regio- and enantioselectivities in the Pd-catalyzed allylic

• ). Good regioselectivity (b/l: 81/19) was obtained with 2-buten-3-yl carbonate as a substrate (entry 14, Table 2). We conducted some control experiments to probe the effect of the bis(trifluoromethyl) group in the ligands (Scheme 3). With ferrocence-based biphenyl phosphine-oxazoline L2 as the ligand, the

Organocatalytic asymmetric fluorination of α-chloroaldehydes involving kinetic resolution

• Kazutaka Shibatomi,
• Takuya Okimi,
• Yoshiyuki Abe,
• Akira Narayama,
• Nami Nakamura and
• Seiji Iwasa

Beilstein J. Org. Chem. 2014, 10, 323–331, doi:10.3762/bjoc.10.30

• α-chloro-α-fluoro-β-keto esters via the sequential chlorination–fluorination of β-keto esters with the Cu(II) complex of SPYMOX [9], a spiro chiral oxazoline ligand developed by our research group [9][10][11][12]. In that study, we succeeded in determining the absolute stereochemistry of the α

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• reaction conditions showed that cesium fluoride proved the best base. PhI(OAc)2 was the preferred oxidant over other hypervalent iodine compounds or sources of F+ or CF3+; additionally, the presence of a bis(oxazoline) as a ligand was beneficial to the reaction, as well as that of TEMPO to prevent

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• point of the oxazoline [42]. The NICS value of −7.3 ppm pointed to the aromaticity of that ring in Ylide I. These results explain the existence of different regioselectivities for both ylides. Following the same calculation patterns previously shown for the reaction with NPM, the results of the main

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• and 3). Interestingly, the protecting groups were not cleaved, which indicated that reaction conditions are very mild. With allyltrimethylsilane oxazoline 1g was obtained in good yield (82%). From ester and acid derivatives of undecen, isoxazolines were obtained in good yields too (64% and 51

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• compounds 4 and 5 were also confirmed by X-ray structure analysis (Figure 7, Figure 8 and Figure 9). In compound 4 the oxazoline and phenyl rings are approximately coplanar (6°), but the pyrrolidine ring is rotated by 52° with respect to the phenyl ring. The main packing interaction is an offset stacking

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• diphenylamine-linked bis(oxazoline)-Zn(OTf)2 complex was investigated. This tandem reaction afforded functionalized chiral chromans in good yields with moderate to high stereoselectivities (up to 95:5 dr, up to 99% ee). Keywords: asymmetric catalysis; bis(oxazoline); chroman; Friedel–Crafts alkylation; tandem

• -linked bis(oxazoline)-Zn(II) complexes. On the other hand, indole and its derivatives are one of the most intensively investigated classical heterocycles owing to their prevalence in bioactive compounds. Indoles have been successfully utilized in asymmetric Friedel–Crafts reactions with nitroolefin and

• reaction has appeared [50]. Herein, we wish to detail our independent research on the asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction of indoles with nitroolefin enoates catalyzed by bis(oxazoline)-Zn(OTf)2 complexes, resulting in functionalized chiral chromans (dihydrobenzopyrans) in

Rh(III)-catalyzed directed C–H bond amidation of ferrocenes with isocyanates

• Satoshi Takebayashi,
• Tsubasa Shizuno,
• Takashi Otani and
• Takanori Shibata

Beilstein J. Org. Chem. 2012, 8, 1844–1848, doi:10.3762/bjoc.8.212

• enantioselective if chiral bisoxazoline ligands were used. However, the substrate scope of this reaction is narrow because of intramolecular reaction. More recently, chiral oxazoline-directed diastereoselective arylation of ferrocenes was reported based on a Pd(II)-catalyzed oxidative coupling reaction [8]. Most

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• elimination. Palladium–pyridine systems were subsequently investigated with chiral ligands to catalyze enantioselective processes involving alkenylindoles. Several enantioselective indole annulations with formation of a stereogenic quaternary carbon atom were performed by using chiral oxazoline ligands with

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• recently, the application of the transglycosylation reaction was of limited use, due to competing enzyme hydrolysis of the formed glycopeptide/protein. By use of oxazoline transition-state analogue substrates, the rate for the transglycosylation reaction was increased and thereby the slower product

• hydrolysis reaction could be avoided [84][85]. A number of successful preparations of N-glycopeptides and N-glycoproteins have since then been successfully prepared by using oxazoline oligosaccharide donors; the synthesis of a HIV gp120 glycopeptide fragment, the HIV gp41 peptide, and the RNase B

• 39 used in this study contained a mixture of high-mannose glycoforms; by treatment with endoglycosidase H (Endo-H), these glycans could be hydrolytically cleaved leaving the GlcNAc monosaccharide still attached to the protein. By treatment with a complex type glycan oxazoline donor and an Endo-M

Synthesis of axially chiral oxazoline–carbene ligands with an N-naphthyl framework and a study of their coordination with AuCl·SMe₂

• Feijun Wang,
• Shengke Li,
• Mingliang Qu,
• Mei-Xin Zhao,
• Lian-Jun Liu and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 726–731, doi:10.3762/bjoc.8.81

• Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. China 10.3762/bjoc.8.81 Abstract Axially chiral oxazoline–carbene ligands with an N-naphthyl framework were successfully prepared, and their coordination behavior with AuCl·SMe2 was also investigated

• % ee of the (E)-allylation products and 92% ee of the recovered Morita–Baylis–Hillman adducts. These intriguing results stimulated us to further develop the axially chiral oxazoline–carbene ligands 7 with an N-naphthyl framework and to evaluate their coordination with AuCl·SMe2. Results and Discussion

• amide 14a as a mixture of diastereomeric isomers successfully in 91% yield. To our delight, the two diastereomeric isomers with a chiral N-naphthyl axis, (Sa,S)-15a and (Ra,S)-15a, were synthesized from amide 14a according to the classical synthetic method for the preparation of an oxazoline ring, and

Facile synthesis of nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranosides from ManNAc-oxazoline

• Karel Křenek,
• Petr Šimon,
• Lenka Weignerová,
• Barbora Fliedrová,
• Marek Kuzma and
• Vladimír Křen

Beilstein J. Org. Chem. 2012, 8, 428–432, doi:10.3762/bjoc.8.48

• , Czech Republic 10.3762/bjoc.8.48 Abstract The synthetic procedures for a large-scale preparation of o- and p-nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranoside are described. The synthetic pathway employs the glycosylation of phenol with ManNAc oxazoline, followed by nitration of the aromatic moiety

• yielding a separable mixture of the o- and p-nitrophenyl derivative in a 2:3 ratio. Keywords: α-ManNAc; glycosidase; glycosylation; nitrophenyl; oxazoline; Introduction Hexosamines are fundamental structural elements and precursors of the peptidoglycan and membrane lipopolysaccharide layer as well as of

• preparation of glycoproteins [9][10], various alcohol glycosides [11][12], phosphates [13] and oligosaccharides [12]. To the best of our knowledge, glycosylation of phenolic OH with oxazoline has not been accomplished so far. Therefore, we decided to test oxazoline 3 [14] glycosylation in our synthetic