Oxazoline ligands reaction

Evans and co-workers investigated the effect of a number of -symmetric bis(oxazoline) ligands on the copper(II)-catalysed Diels-Alder reaction of an N-acyloxazolidinone with cyclopentadiene. Enantiomeric excesses of up to 99% have been reported (Scheme 3.4). Evans et al." suggested transition state assembly 3.7, with a square planar coordination environment around the central copper ion. In this scheme the dienophile should be coordinated predominantly in an cisoid fashion in... 

Recently Desimoni et used the same bis(oxazoline) ligand in the magnesium(II) catalysed Diels-Alder reaction of the N-acyloxazolidinone depicted in Scheme 3.4. In dichloromethane a modest preference was observed for the formation of the S-enantiomer. Interestingly, upon addition of two equivalents of water, the R-enantiomer was obtained in excess. This remarkable observation was interpreted in terms of a change from tetrahedral to octahedral coordination upon the introduction of the strongly coordinating water molecules. 

Since Evans s initial report, several chiral Lewis acids with copper as the central metal have been reported. Davies et al. and Ghosh et al. independently developed a bis(oxazoline) ligand prepared from aminoindanol, and applied the copper complex of this ligand to the asymmetric Diels-Alder reaction. Davies varied the link between the two oxazolines and found that cyclopropyl is the best connector (see catalyst 26), giving the cycloadduct of acryloyloxazolidinone and cyclopentadiene in high optical purity (98.4% ee) [35] (Scheme 1.45). Ghosh et al., on the other hand, obtained the same cycloadduct in 99% ee by the use of unsubstituted ligand (see catalyst 27) [36] (Scheme 1.46, Table 1.19). 

Rhodium complexes with chelating bis(oxazoline) ligands have been described to a lesser extent for the cyclopropanation of olefins. For example, Bergman, Tilley et al. [32] have prepared a family of bis(oxazoline) complexes of coordinatively unsaturated monomeric rhodium(II) (see 20 in Scheme 13). Interestingly, the use of complex 20 in the cyclopropanation reaction of styrene afforded mainly the cis cyclopropane cis/trans = 63137), with 74% ee and not the thermodynamically favored trans isomer. No mechanistic suggestions are proposed by the authors to explain this unusual selectivity. 

Apart from the cyclopropanation reaction, only one example has been published of the application of ionic liquids as reaction media for enantio-selective catalysis with bis(oxazoline) ligands. In this case, the complex 6b-ZnCl2 was used as a catalyst for the Diels-Alder reaction between cyclopen-tadiene and N-crotonyloxazolidin-2-one in dibutyUmidazoUiun tetrafluorob-orate (Scheme 9) [48]. Compared with the same process in CH2CI2, the reaction was faster and both the endofexo selectivity and the enantioselectivity in the endo product were excellent. However, experiments aimed at recovering the catalysts were not carried out. 

Scheme 1.24 Test reaction with sulfanylmethyl-, aryl-, and thiophene-oxazoline ligands.

Scheme 1.25 Test reaction with sulfoxide-oxazoline ligands.

Scheme 1.26 Test reaction with dibenzothiophene or benzothiophene-oxazoline ligands.

In 1999, Ikeda et al. reported a new type of sulfur-oxazoline ligands with an axis-fixed or -unfixed biphenyl backbone prepared in good yields by coupling reactions of methoxybenzene derivatives substituted with a chiral oxazoline and a sulfur-containing Grignard reagent. These ligands were subsequently evaluated for the test palladium-catalysed asymmetric allylic alkylation... 

Scheme 1.27 Test reaction with axial sulfur-oxazoline ligands with biphenyl backbone.

Scheme 1.31 Test reaction with thioglucose-oxazoline ligands.

Scheme 1.32 Test reaction with tetrathiafulvalene-oxazoline ligands.

Scheme 1.54 Test reaction with dibenzothiophene-bis(oxazolines) ligands.

Asymmetric Lewis-Acid Catalyzed. Another important advance in aqueous Mukaiyama aldol reaction is the recent success of asymmetric catalysis.283 In aqueous ethanol, Kobayashi and co-workers achieved asymmetric inductions by using Cu(OTf)2/chiral >A(oxazoline) ligand,284 Pb(OTf)2/chiral crown ether,285 and Ln(OTf)3/chiral Mv-pyridino-18-crown-6 (Eq. 8.105).286... 

Recently, very effective asymmetric conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes has been reported, as shown in Scheme 4.10. The reaction of ethyl acetoacetate with nitrostyrene is carried out in the presence of 5 mol% of the preformed complex of magnesium triflate and chiral bis(oxazoline) ligands and a small amount ofW-methylmorpholine (NMM) to give the adduct with selectivity of 91%. The selectivity depends on ligands. The effect of ligands is presented in Scheme 4.10.63... 

Aromatic and vinylic sulfides take part in cross-coupling reactions with Grignard reagents in the presence of Ni catalysts.336,337 This reaction has been applied to the enantioselective synthesis of binaphthyls using a standard chiral oxazoline ligand (Equation (25)) 338... 

In stereoselective reactions, Zn11 Lewis acids work well to achieve high selectivities (Scheme 54). Chiral complexes of Zn11 with chiral bis(oxazoline) ligands act as effective catalysts in Diels-Alder reactions of reactive dienes with dienophiles having bidentate chelating moieties such as... 

Catalytic asymmetric aldol reactions of a-heterosubstituted substrates such as glyoxaldehyde, and methyl pyruvate have been reported (Scheme 81). High diastereo- and enantioselectivity have been obtained by using combined use of Sn(OTf)2 and bis(oxazoline) or pyridinebis(oxazoline) ligands.341... 

The palladium-catalyzed asymmetric allylic substitution using seven different phosphano-oxazoline ligands at various ligand-to-metal ratios was also studied.112 An aluminum block containing 27 wells was placed in a dry box in which the reactions were carried out in parallel. Analyses were performed by conventional chiral GC equipped with an autosampler. Such a setup allowed about 33 catalyst evaluations per day. Apparently, only a few dozen were carried out in the study, resulting in the identification of a catalyst showing an ee-value of 74% in the reaction of 4-acyloxy-2-pentene with malonate.112 It is not clear whether further ligand diversification would lead to catalysts more selective than the record set in this case by the Trost-catalyst (92% ee).113... 

An alternative protocol for treating alkylzinc bromides with primary and secondary alkyl bromides and iodides was described by Zhou and Fu.409 In the study, a combination of Ni(cod)2 and a chiral oxazoline ligand 306 was used as a catalytic system providing 62-88% yield of product 307 A,A-dimethylacetamide (DMA) was the reaction solvent (Scheme 156). 

Recently, asymmetric NHK reactions have been investigated. Among them, catalytic versions of this reaction have been successful a Cr-chiral salen complex 127,226-228 a Cr-chiral sulfonylamide complex 128,229 a Cr-tridentate ligand 129 complex,230,231 and a Cr-chiral oxazoline ligand 130 complex232 were found to be effective to achieve good to high enantioselectivity (Scheme 57). 

The C2-symmetric bis(oxazoline)-Cu(II) complexes have proved to be very effective in asymmetric aldol reactions (see Section 3.4.3), as well as Diels-Alder reactions (see Section 5.4.6). These compounds are also powerful catalysts in hetero Diels-Alder reactions. Figure 5-8 shows some of the bis(oxazoline) ligands applied in asymmetric hetero Diels-Alder reactions. 

Figure 5-8. Bis(oxazoline) ligands used in asymmetric hetero Diels-Alder reactions.

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