Asymmetric epoxidation stoichiometry

Two aspects of stoichiometry are important in asymmetric epoxidation one is the ratio of Ti to tartrate used for the catalyst and the other is the ratio of catalyst to substrate. With regard to the... 

The second stoichiometry consideration is the ratio of catalyst to substrate. As noted in the preceding section, virtually all asymmetric epoxidations can be performed with a catalytic amount of Ti-tartrate complex if molecular sieves are added to the reaction milieu. A study of catalyst/substrate ratios in the epoxidation of cinnamyl alcohol revealed a significant loss in enantioselectivity (Table 6A.2) below the level of 5 mol % catalyst. At this catalyst level, the reaction rate also decreases, with the consequence that incomplete epoxidation of the substrate may occur. Presendy, the recommended catalyst stoichiometry is from 5% Ti and 6% tartrate ester to 10% Ti and 12% tartrate ester [4],... 

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... 

Chiral sulfoxides. The Sharpless reagent lor asymmetric epoxidation also effects asymmetric oxidation of prochiral sulfides to sulfoxides. The most satisfactory results are obtained for the stoichiometry Ti(0-(-Pr)4/L DET/H20/(CH,),C00H = 1 2 1 2 for I equiv. of sulfide. In the series of alkyl p-tolyl sulfides, the (R)-sulfoxide is obtained in 41-90% ee the enantioselectivity is highest when the alkyl group is methyl. Methyl phenyl sulfide is oxidized to the (R)-sulfoxide in 81% ee. Even optically active dialkyl sulfoxides can be prepared in 50-71% ee the enantioselectivity is highest for methyl octyl sulfoxide. 

Two aspects of stoichiometry are important in an asymmetric epoxidation one is the ratio of titanium to tartrate used for the catalyst and the other is the ratio of catalyst to substrate. With regard to the catalyst, it is crucial to obtaining the highest possible enantiomeric excess that at least a 10% excess of tartrate ester to titanium(IV) alkoxide be used in all asynunetric epoxidations. This is important when the reaction is being done with either a stoichiometric or a catalytic quantity of the complex. There appears to be no need to increase the excess of tartrate ester beyond 10-20% and, in fact, a larger excess has been shown to slow the epoxidation reaction unnecessarily. ... 

The original report32 of the titanium-catalyzed asymmetric epoxidation of allylic alcohols in 1980 has been followed by hundreds of applications, the majority of which use the initially reported conditions. In the decade since the introduction of this reaction numerous improvements have been made41. The most complete discussion of the preparative aspects of both the asymmetric epoxidation and the kinetic resolution was presented by the Sharpless group42. This paper details the effects of reagent stoichiometry and concentration, substrate concentration, aging of the catalyst and variation of oxidant, solvent and tartrate as well as workup procedures. What is particularly noteworthy in this presentation is that significant amounts of unpublished work are drawn upon to develop recommendations for successful reaction. 

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