Alkenes Kharasch-Sosnovsky reaction

Scheme 8. General mechanism of the copper-catalyzed allylic oxidation of alkenes (Kharasch-Sosnovsky reaction).

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. 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

The allylic acyloxylation of alkenes, the Kharasch-Sosnovsky reaction, Eq. 81, would be an effective route to nonracemic allylic alcohol derivatives, if efficient, enantioselective catalysts were available. The reaction is mediated by a variety of copper salts, and as such, has been the target of considerable research in an attempt to render the process enantioselective. The original reaction conditions described by Kharasch require high temperatures when CuBr is used as the catalyst (93). However, the use of CuOTf (PhH)0 5 allows the reaction to proceed at temperatures as low as -20°C. Unfortunately, long reaction times are endemic in these processes and the use of excess alkene (2-100 equiv) is conventional. Most yields reported in this field are based on the oxidant. 

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

The development of ruthenium complexes for other applications in radical chemistry is still in its infancy, but seems well suited to future expansion, thanks to the versatility of ruthenium as a catalytically active center. Large avenues have not been explored yet and remain open to research. For instance, the development of methodologies for the asymmetric functionalization of C-H bonds remains a challenge. The Kharasch-Sosnovsky reaction [51,52],in which the allylic carbon of an alkene is acyloxylated, its asymmetric counterpart, and the asymmetric version of the Kharasch reaction itself are practically terra incognita to ruthenium chemistry, and await the discovery of improved catalysts. 

The direct oxidation of unfunctionahsed alkanes in an asymmetric fashion is a formidable challenge. However, oxidation of C—H bonds adjacent to suitable functional groups gives a handle on which to operate. In particular, the aUyKc oxidation of cyclic alkenes utilising asymmetric variants of the Kharasch—Sosnovsky reaction has received considerable attention. The reaction is catalysed by copper salts and requires a perester to give the allylic ester as product. 

Scheme 5.69 Cu-catalyzed asymmetric Kharasch-Sosnovsky reactions with acyclic alkenes reported by Singh.

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