Hydroxyamines resolution

Thiols may be enantioselectiveiy added in a conjugate fashion to a,p-unsaturated carbonyl compounds in the presence of chiral hydroxyamine catalysts e.g. chinchona alkaloids).242,244 249 252-261-269 In some cases ee of up to >80% were achieved e.g. Scheme 77).242-261-262 This methodology was utilized for the kinetic resolution of compound rat-86 Scheme 34) in a multigram scale.94 Related enantioselective 1,4-additions of thioacetates270-271 and selenophenols272 to enones are also known. Epoxidations, based on the asymmetric nucleophilic addition of peroxide anions to enones, are discussed separately.273... 

The [3-hydroxy amines are a class of compounds falling within the generic definition of Eq. 6A.6. When the alcohol is secondary, the possibility for kinetic resolution exists if the Ti-tartrate complex is capable of catalyzing the enantioselective oxidation of the amine to an amine oxide (or other oxidation product). The use of the standard asymmetric epoxidation complex (i.e., T2(tartrate)2) to achieve such an enantioselective oxidation was unsuccessful. However, modification of the complex so that the stoichiometry lies between Ti2 (tartrate) j and Ti2(tartrate)1 5 leads to very successful kinetic resolutions of [3-hydroxyamines. A representative example is shown in Eq. 6A.11 [141b,c]. The oxidation and kinetic resolution of more than 20 secondary [3-hydroxyamines [141,145a] provides an indication of the scope of the reaction and of some... 

The kinetic resolution of racemic tertiary P-hydroxyamines by enantioselective /V-oxide formation was developed by the Sharpless group as a corollary of the allylic alcohol epoxida-... 

In a related reaction using a different Ti(OlV)4/DIPT catalyst it was found that kinetic resolution of racemic /6-hydroxy amines could be effected by enantioselective A-oxide formation. The A-oxide could be reduced to the chiral (S) j6-hydroxyamine using LiAlH4 in THF or by catalytic hydrogenation. In addition 2,3-epoxyalcohols... 

Structural limitations to good kinetic resolution. These results also show a consistent correlation of absolute configuration of the resolved hydroxyamine with the configuration of tartrate used in the catalyst This correlation is as shown in Eq. 6A.11, where use of (+)-DIPT results in oxidation of the (5)-P-hydroxyamine and leaves unoxidized the (/ )-enantiomer. 

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