Chiral monooxazolines as modular copper(I)-heterocomplex building blocks: investigations on the catalytic asymmetric cyclopropanation of alkenes (original) (raw)

Further Developments and Applications of Oxazoline-Containing Ligands in Asymmetric Catalysis

Chemical Reviews

The chiral oxazoline motif is present in many ligands that have been extensively applied in a series of important metal-catalyzed enantioselective reactions. This Review aims to provide a comprehensive overview of the most significant applications of oxazoline-containing ligands reported in the literature starting from 2009 until the end of 2018. The ligands are classified not by the reaction to which their metal complexes have been applied but by the nature of the denticity, chirality, and donor atoms involved. As a result, the continued development of ligand architectural design from mono(oxazolines), to bis(oxazolines), to tris(oxazolines) and tetra(oxazolines) and variations thereof can be more easily monitored by the reader. In addition, the key transition states of selected asymmetric transformations will be given to illustrate the features that give rise to high levels of asymmetric induction. As a further aid to the reader, we summarize the majority of schemes with representative examples that highlight the variation in % yields and % ees for carefully selected substrates. This Review should be of particular interest to the experts in the field but also serve as a useful starting point to new researchers in this area. It is hoped that this Review will stimulate both the development/design of new ligands and their applications in novel metal-catalyzed asymmetric transformations.

Isbut-Box: A new chiral C2 symmetric bis-oxazoline for catalytic enantioselective synthesis

Journal of Molecular Catalysis A: Chemical, 2005

A series of chiral non-racemic isobutylene bis-oxazoline (Isbut-Box) ligands have been synthesised in satisfactory overall yields. The utility of such ligands for catalytic asymmetric synthesis has been demonstrated using the Cu(I) catalysed enantioselective cyclopropanation of styrene and derivatives with ethyl diazoacetate as a test reaction. The Cu(I) moiety is generated in situ using ethyl diazoacetate prior to the addition of the olefin. In these preliminary studies, the aforementioned cyclopropanation reaction gave yields, enantioselectivities and diastereoselectivities of up to 69%, 70% ee and 72% de. The reaction results were shown to be solvent dependent, with dichloromethane demonstrating good yields and toluene showing good stereoselectivities. DFT studies and NMR spectroscopic studies were undertaken to probe the structure and behaviour of the Cu(I)-Isbut-Box ligands.

Synthesis of a Novel C2-Symmetric Bis-oxazoline (=Bis[4,5-dihydrooxazole]) and Its Application as Chiral Ligand in Asymmetric Transition Metal Catalysis

Helvetica Chimica Acta, 2012

The new C 2-symmetric bis-oxazoline (¼ bis[4,5-dihydrooxazole]) 2 with a chiral trans-(2R,3R)-2,3bis(3,5-diphenylphenyl)cyclopropylidene (¼ trans-(2R,3R)-2,3-bis([1,1': 3',1''-terphenyl]-5'-yl)cyclopropylidene) backbone was efficiently synthesized (Scheme). All synthetic steps were easy to perform and led to the desired product in good overall yields. Compound 2 was tested and compared as ligand in several enantioselective catalytic reactions such as palladium(0)-catalyzed enantioselective allylic alkylations and copper(I)-catalyzed enantioselective cyclopropanations and aziridinations.

Immobilized oxazoline-containing Ligands in asymmetric catalysis—a review

Bioorganic & Medicinal Chemistry Letters, 2002

Metal complexes of chiral oxazoline derivatives immobilized on soluble as well as insoluble supports serve as versatile asymmetric catalysts in a variety of applications. In a few cases recovery and reuse of the chiral ligands have been achieved.

Synthesis of a Family of Fine-Tunable New Chiral Ligands for Catalytic Asymmetric Synthesis. Ligand Optimization through the Enantioselective Addition of Diethylzinc to Aldehydes

The Journal of Organic Chemistry, 1997

A family of enantiomerically pure (1R,2R)-1-(dialkylamino)-1-phenyl-3-(R-oxy)-2-propanols (4) has been synthesized from (2S,3S)-2,3-epoxy-3-phenylpropanol (1a), arising from the Sharpless epoxydation of cinnamyl alcohol, by two alternative sequences involving either the regioselective ring opening of the epoxide by a secondary amine (C-3 attack) and subsequent chemoselective protection of the primary hydroxy group or the reverse of these operations. A total of 19 different derivatives 4 have been prepared in an iterative process aimed at the optimization of their catalytic properties in the enantioselective addition of diethylzinc to benzaldehyde. In doing this, the steric bulk of the R-oxy group and the choice of the dialkylamino substituent as a nitrogen-containing six-membered ring have been identified as the key structural parameters for high catalytic activity and enantioselectivity in 4. Two optimized ligands fulfilling these structural requirements, 4d-Tr (R-oxy ) trityloxy, dialkylamino ) piperidino) and 4i-Tr (R-oxy ) trityloxy, dialkylamino ) 4-methylpiperazin-1-yl), depict a convenient activity and selectivity profile in the addition of Et 2 -Zn to a structurally diverse family of aldehydes. These results show how chiral ligands based on non-natural starting materials can accommodate subtle variations of the steric/electronic characteristics key to the fine tuning of catalytic properties and thus represent a convenient alternative to ligands based on natural products. For compilations of natural and non-natural enantioselective catalysts and auxiliaries, see, for example: (a) Blaser, H. U. Chem. Rev. 1992, 92, 935-952. (b) Chiral Auxiliaries and Ligands in Asymmetric Synthesis; Seyden-Penne, J., Ed.; John Wiley & Sons, Inc.: New York, 1995. (4) (a) Canas, M.; Poch, M.; Verdaguer, X.; Moyano, A.; Pericàs, M. A.; Riera, A. Tetrahedron Lett. 1991, 32, 6931-6934. (b) Poch, M.; Verdaguer, X.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron Lett. 1991, 32, 6935-6938. (c) Alcón, M.; Canas, M.; Poch, M.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron Lett. 1994, 35, 1589-1592. (d) Poch, M.; Alcón, M.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron Lett. 1993, 34, 7781-7784. (e) Castejón, P.; Pastó, M.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron Lett. 1995, 36, 3019-3022. (f) Pastó, M.; Moyano, A.; Pericà s, M. A.; Riera, A. Tetrahedron: Asymmetry 1995, 6, 2329-2342. (g) Pastó, M.; Moyano, A.; Pericàs, M. A.; Riera, A.

Bifunctional bis(oxazolines) as potential ligands in catalytic asymmetric reactions

Canadian Journal of Chemistry, 2004

C 2-symmetrical bis(oxazoline) ligands bearing pendant alkylthio ether groups were synthesized, and the structures of Cu complexes were determined by single crystal X-ray diffraction. The potential utility in catalysis was shown in the asymmetric addition of methyllithium to an aromatic aldimine, which resulted in a mixture of products with an enantiomeric excess of 68%.

4-Naphthyl-substituted bis(oxazoline): A new, easily recoverable and efficient chiral ligand in asymmetric catalysis of the Diels-Alder reaction

Tetrahedron, 1998

2,2-Bis{2-[(4R)-(2'-naphthyl)-l,3-oxazolinyl]}propane and its (43) enantiomer were prepared stsr~ 8 from 2-vinylrmphthalene, following the Sharpless protocol, and were found to be optically pure (ee > 99.5%) by hplc analysis. These new bis(oxazolines) are efficient chiral ligands in the asymmetric catalysis of the Diels-Alder reaction of Nalkenoyl-oxazolidin-2-one derivatives since endo cycloadducts are obtained with up to 94% ee. Different Lewis acids were tested, the best one being the Mg(H) cation derived from the corresponding triflate. A remarkable feature of such new chiral ligands is the low solubility in polar solvents, so that the chiral ligand can be easily recovered by a simple filtration. The recovered iigand can be directly reused in other asymmetric syntheses, without any further purification and, overall, without any drop in the induced enantioselectivities.

Asymmetric Henry reactions catalyzed by metal complexes of chiral oxazoline based ligands

Chiral oxazolines have been synthesized from norephedrine and pyrrole nitrile or benzoyl chloride and applied to the catalytic asymmetric Henry reactions of p-nitro aldehydes with nitromethane to provide b-hydroxy nitroalkanols in high conversion (up to 92%). The reaction was then optimized in terms of the metal, solvent, temperature, and amount of chiral ligand. The corresponding catalyst with Cu(OTf) 2 and isopropanol as the solvent gave the best enantioselectivities (up to 84% ee) of the corresponding b-nitroalkanol for p-nitrobenzaldehyde.