Oxazoline-based chiral

QM/MM calculations and experimental kinetic study have explored the effects of solvation on the transition states for reaction between nitromethane and formaldehyde and between nitropropane and benzaldehyde. Asymmetric reactions of nitromethane with various aldehydes have been promoted by Cu(II) coordinated with amino alcohols, 0 imidazolium/pyrrolidinium-tagged Indabox, and imidazolium-taggedbis(oxazoline)-based chiral ligands. The Henry reaction has also been promoted by Mn(OAc)2/Schiff bases bearing a triazole structure, with up to 99% yield, and by phosphonium ionic ligands MeP+(octyl)3 R0C02 without solvent. ... 

Chiral oxazoline-based synthetic methods have been employed in the asymmetric synthesis of a large number of natural products. A few representative examples of these applications are shown below. 

Similar results were reported by the Barret group by using stoichiometric amounts of an enantiopure 2-(2-pyridinyl)-2-oxazoline [46], hi 1996, Iseki and Kobayashi achieved a catalytic version of the asymmetric allylation [47], They applied proline-based chiral HMPA derivatives for the allylation. The catalyst 21 proved to be the best one regarding catalyst loading down to 1 mol% (Scheme 16) [48],... 

Alkylation of the 2-methyl-2-oxazoline (base/electrophile) results in homologated 2-oxazolines. A second alkylation sequence proceeds with asymmetric induction and results in the formation of highly substituted chiral 2-alkyl alkanoic acids. Use of ethylene oxide as the electrophile in this process allows for the formation of chiral a-substituted y-butyrolactones and a-substituted 7-valerolactones with good stereoselectivity (60-80% ee eq 3). ... 

The chiral nitrogen-phosphine ligands represent the most flourishing bitopic auxiliaries. They can be divided into five classes closely related to their skeletons, which are binaphtyl-, pyridine-, metallocene-, amine-, or oxazoline-based. Much attention has been given to the last class, which has led to a spectacular... 

Scheme 8 Hydrogenation of terminal olefins with oxazoline-based catalysts bearing an axial chiral biarylphosphite moiety. Full conversion was observed for all entries...

Serrano and co-workers have reported the synthesis of two interesting series of chiral, hexacatenar metal complexes, that is, mono- and dinuclear, derived from chiral oxazoline-based ligands.None of the pure dinuclear compounds (136 X = OAc, Cl) was mesomorphic and most were room-temperature oils or glassy materials. This is likely due to the sterically demanding central chiral unit preventing molecular stacking and, hence, mesophase formation. 

Various oxazoline-based organocatalysts were prepared and applied to enantioselective Strecker reactions of different N-benzhydrylimines with TMSCN. In particular, derivative 156 allowed the synthesis a-amino nitriles in high yield and with excellent chiral induction (13CEJ14224). 

Fig. 5 Examples of quenching enantioselective sensors involving metal ions (a) JV.W -dioxide of the 1,8-diacridylnaphtalene units which can form a scandium(m) complex (b) high enantioselective quenching obtained by the scandium complex of 11 for 2-aminopropanol (reprinted with permission from [64]. Copyright 2008 American Chemical Society) (c) triamino-diamido copper (II) complex (12) (d) Zn (II) complex with terpyridine based chiral ligand (13) (e) chiral oxazoline containing maleimido polymers (14)...

During the course of their pioneering work on the copper-catalyzed cyclopropanation reaction of alkenes [25], the copper-catalyzed aziridination of alkenes using PhI=NTs was also discovered by Evans et al. in 1991 [26], A wide range of alkenes can be smoothly converted to the corresponding aziridines in the presence of Cu(I) and Cu(II) salts, such as Cu(MeCN)4C104 and Cu (acac)2, respectively (Scheme 2.16). Notably, aliphatic alkenes afforded the desired aziridines without allylic C-H amidation products. In the hterature, only one example of the enantioselective aziridination of styrene using chiral bis (oxazoline)-based copper catalyst was demonstrated. At the... 

In contrast with the impressive evolution of asymmetric reactions with paUadium(0) catalyst, palladium(II)-catalyzed asymmetric Wacker-type oxidations have received only scant attention. For instance, Alper and Hamel and Cao and Zhang described asymmetric Pd(II)-catalyzed car-bonylation of aUyUc alcohols. Chiral bis(oxazolines) based on binaphtyl (Boxaxs ) or biphenyl backbone were also successfiiUy applied in the asymmetric Wacker-type cycUzation of aUylphenoIs. Sasai and co-workers reported on the oxidative cychzation of alkenyl alcohols with spiro bis(isoxazolines) (SPRIXs). ... 

Recently, camphor-based oxazolines have been applied as chiral Michael acceptors401 402... 

Other asymmetric syntheses, based on aldol condensation of chiral a-sulfinyl carbanions with carbonyl compounds, are the formation of / -hydroxyketones from /J-sulfinylhydrazones 166211-214, of /3, /l -dihydroxyketones from 3-(p-tolylsulfinyl-methyl)-A2-methylisoxalinones 167215, of /1-hydroxyacids from 2-(p-tolylsulfinylmethyl)oxazolines 168216 and of /J-hydroxyesters from ethyl-p-tolylsulfinyl-W-methoxyacetamide 169217. 

In conclusion, many chiral pyridine-based ligands have been prepared from the chiral pool and have been successfully tested as ligands for the copper- or rhodium-catalyzed cyclopropanation of olefins. Alfhough efficient systems have been described, sometimes leading interestingly to the major cis isomer, the enantioselectivities usually remained lower than those obtained with the copper-bis(oxazoline) system. 

---