Kharasch-Sosnovsky reaction, -2-oxazoline

The use of bis(oxazoline) ligands in the Kharasch-Sosnovsky reaction proved to be beneficial, affording well-behaved catalysts. The original investigations were communicated independently and concurrently by Pfaltz and co-workers (108) and Andrus et al. (109). 

Asymmetric allylic oxidation and benzylic oxidation (Kharasch-PSosnovsky reaction) are important synthetic strategies for constructing chiral C—O bonds via C—H bond activation.In the mid-1990s, the asymmetric Kharasch-Sosnovsky reaction was first studied by using chiral C2-symmetric bis(oxazoline)s. " Later various chiral ligands, based mainly on oxazoline derivatives and proline derivatives, were used in such asymmetric oxidation. Although many efforts have been made to improve the enantioselective Kharasch-Sosnovsky oxidation reaction, most cases suffered from low to moderate enantioselectivities or low reactivities. 

TABLE 31. Results of the Cu/oxazoline-catalyzed Kharasch-Sosnovsky reaction of various alkenes (yields are given and ee values are given in parentheses)... 

SCHEME 128. Catalytic enantioselective Kharasch-Sosnovsky reaction catalyzed by different Cu-oxazoline chiral complexes... 

Allylic Oxidation. The Kharasch-Sosnovsky reaction involves oxidation of the allylic position while the olefin remains intact. In the presence of catalytic copper (II) salts, treatment of olefins with peresters affords acylated allylic alcohols. When (S)-(—)-4-(2-methylpropyl)-2-(2-pyridyl)-2-oxazoline was involved, (R)-cyclohexenyl benzoate was isolated in 57% yield and 28% ee (eq 6). ... 

Scheme 11. Asymmetric Kharasch-Sosnovsky reaction using bis- or tris(oxazoline) as a chiral auxiliary...

Garcia, Reiser, and co-workers developed an easily recoverable and reusable catalytic system based on a ditopicazabis(oxazoline) ligand L40 for the enantioselective Kharasch-Sosnovsky reaction. When the reaction was complete in MeCN or BTFEP, the ligand and Cu salt were able to form insoluble coordination polymers which precipitated after extraction with hexane. This method allows up to four successive uses of the catalysts without loss of catalytic activity. 

Oxazolines are nowadays essential ligands in asymmetric catalysis and also important synthons for stereoselective synthesis [8]. The success of the Cj-symmetric bis(oxazolines) ( BOX ) and pyridine-bis(oxazolines) ( Pybox ) discovered in the early 1990s has established them as a privileged class of ligands [9]. In contrast, the development and application of trisoxazolines lagged behind for a long time. Katsuki and collaborators [10] reported the first example of a chiral trisoxazoline in 1995 and their use in the allylic oxidation of alkenes (Kharasch-Sosnovsky reaction), as well as the enantioselective addition of diethylzinc to aldehydes. 

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