Kharasch-Sosnovsky reaction, copper

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. 

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

The application of dinuclear metal catalysts to the Kharasch-Sosnovsky reaction is mechanistically intriguing due to their illustrated role in mediating biological oxidations (119). Fahmi (120) examined a variety of dinucleating ligands with Cu(MeCN)4PF6 as catalysts in the allylic oxidation of cyclohexene, Eq. 102. In these studies, early results have been inferior to those obtained from bis(oxa-zoline)-copper catalysts. 

Although the first example of an asymmetric Kharasch-Sosnovski reaction with a chiral perester was reported as early as 1965 [17], major advances have only been made in the last ten years. In the early 1990s, Muzart carefully reinvestigated earlier results obtained by Araki and Nagase [18]. After intensive optimization of the reaction conditions, the acyloxylation of cydopentene and cyclohexene gave products with up to 59 and 45 % ee, respectively. The best conditions for the oxidation of cyclohexene were found to involve the use of 5 mol% copper oxide, 10 mol% proline (1), and tert-butyl perbenzoate/benzoic acid in benzene under reflux (Scheme 2) [19]. 

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). ... 

The oxidative transformation of dihydrooxazoles to oxazoles has also been achieved using the Kharasch-Sosnovsky reaction <94TL6803>. The first step is a hydrogen atom abstraction by a species generated from a copper-ion catalyzed (CuBr) decomposition of a peroxyester (Bu OOC(O)Ph). Yields are better when a copper(II) species is added, perhaps because of faster reaction with the radical intermediate (135) (Scheme 61). 

In 1965, Denny et al. for the first time reported a catalytic asymmetric Kharasch-Sosnovsky reaction by using Cu(II)-(a)-ethyl camphorate as a catalyst, though enantioselectivity was low (Scheme 9) [21]. A quarter of a century later, natural or synthetic amino acids were introduced as chiral auxiliaries and much improved enantioselectivity (up to 65% ee) was achieved (Scheme 10) [22]. Although no detailed information on the structures of these copper complexes has been obtained, the observed non-linear relationship between the ee of the chiral auxiliary and the ee of the product suggests that the copper-amino acid complex is not monomeric but instead is oligomeric (at least dimeric) species [22e]. 

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. 

Reaction with unsaturated compounds (reviews Kharasch,Sosnovsky,andYang reported that, in the presence of a catalytic amount of a copper or cobalt salt, t-butyl perbenzoate reacts with an olefin to give an allylic benzoate with no allylic rearrangement with a terminal olefin the only product isolated was the allylic ester with a terminal double bond. A further example is the reaction with 1-methylene-4-f-butylcyclohexane. However, in contrast to these early reports, Kochi found by o... 

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