Oxazoline ligands asymmetric Heck reactions

Excellent enantioselectivity and double-bond regioselectivity can be achieved in an asymmetric Heck reaction between 2,3-dihydrofuran and aryl triflates by using a combination of chiral diphosphine-oxazoline ferrocenyl ligand and Pd catalyst <03CEJ3073>, as shown below. Chiral diphosphine-containing (arene)tricarbonylchromium(O) complexes were also used as ligands for this reaction to obtain the 2,3-isomer, however, both the yield and enantioselectivity were modest <03TA1455>. 

The intramolecular asymmetric Heck reaction has featured in the synthesis of complex heterocyclic compounds. Bidentate ligands, such as diphosphines (especially BINAP) and phosphine—oxazolines, have been used as a chiral ligand of the asymmetric Heck reaction. Imbos et al. demonstrated that the mono-dentate phosphoramidite 513 was an effective ligand for the asymmetric Heck reaction of the prochiral cyclohexadienone 511 (Scheme 153).227 The reaction of 511 in the presence of catalytic amounts of Pd-(OAc)2 and the chiral phosphoramidite 513 gave the 4a-methoxy-4a//-benzo[c]chromen-2(6E/)-one 512 in 71% yield with 96% ee. By contrast, the reaction of... 

Hashimoto, Y, Horie, Y, Hayashi, M. and Saigo, K. (2000) An efficient phosphorus-containing oxazoline ligand derived from cw-2-amino-3,3-dimethyl-l -indanol application to the palladium-catalyzed asymmetric Heck reaction. Tetrahedron Asymmetry, 11, 2205-10. 

Mata, Y, Dieguez, M., Pamies, O. and Claver, C. (2005) Chiral phosphite oxazolines class of ligands for asymmetric Heck reactions. Org. Lett., 7, 5597-9. 

Another significant point of interest in the microwave enhanced Heck reaction is the asymmetric induction. A highly modular library of readily available phosphate oxazoline ligands was applied in the Pd-catalyzed asymmetric Heck reactions of several substrates and triflates under thermal and microwave conditions. Both enantiomers of the Heck coupling products showed excellent regioselective and enanti-oselective activities (Mazuela et al., 2010). 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

Mata Y, Pamies O, Dieguez M (2007) Screening of a modular sugar-based phosphite-oxazoline ligand library in asymmetric Pd-catalyzed heck reactions. Chem-Eur J 13 3296-3304... 

Hou and coworkers [25] synthesized novel diphosphine oxazoline fenocenyl ligands 31 and applied these to the asymmetric intermolecular Mizoroki-Heck reaction of 2,3-dihydrofuran (1) with aryl triflates. The ligands can have three possible binding modes with palladium (Scheme 11.16). 

Pfaltz and coworkers [43] developed P,N ligands 73 and 74 derived from pyridine and quinoline. They reasoned that oxazoline and pyridine/quinoline ligands, since they have different electronic effects, would induce different patterns of reactivity and selectivity in the asymmetric Mizoroki-Heck reaction. In the reaction of phenyl triflate (2) with... 

Tu, T., Deng, W.-R, Hou, X.-L. et al. (2003) The regioselectivity of the asymmetric intermolecular Heck reaction with planar chiral diphosphine-oxazoline ferrocenyl ligands. Chem. Eur. J., 9, 3073 1. 

In 1999, Mikami s group reported the first example of an intermolecular asymmetric Fujiwara-Moritani reaction of benzene with cyclic alkenes using a Pd catalyst co-ordinating to a chiral sulfonylamide-oxazoline ligand (Scheme 7.24). With PhCOs Bu as the oxidant, the coupling reaction occurred with moderate enantioselectivity (up to 49% ee), although the chemical yield was low. The reaction is considered to involve the formation of a phenyl-Pd species via electrophilic C-H substitution by Pd(ii), and Heck-type cyclization followed by re-oxidation of the resultant Pd(0) species. 

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