Ferf-Butyl hydroperoxide, Sharpless

The asymmetric epoxidation of an allylic alcohol 1 to yield a 2,3-epoxy alcohol 2 with high enantiomeric excess, has been developed by Sharpless and Katsuki. This enantioselective reaction is carried out in the presence of tetraisopropoxyti-tanium and an enantiomerically pure diaUcyl tartrate—e.g. (-1-)- or (—)-diethyl tartrate (PET)—using ferf-butyl hydroperoxide as the oxidizing agent. 

The Sharpless epoxidation uses ferf-butyl hydroperoxide, titanium(IV) isopropoxide, and a dialkyl tartrate ester as the reagents. The following epoxidation of geraniol is typical. 

Sharpless asymmetric epoxidation ° is an enantioselective epoxidation of an allylic alcohol with ferf-butyl hydroperoxide (f-BuOOH), titanium tetraisopropoxide [Ti(0-fPr)4] and (-b)- or (—)-diethyl tartrate [(-b)- or (—)-DET] to produce optically active epoxide from achiral allylic alcohol. The reaction is diastereoselective for a-substituted allylic alcohols. Formation of chiral epoxides is an important step in the synthesis of natural products because epoxides can be easily converted into diols and ethers. 

The step marked A is similar to the ene synthesis (15-23). The step marked B is a [2,3]-sigmatropic rearrangement (see 18-35). The reaction can also be accomplished with ferf-butyl hydroperoxide, if Se02 is present in catalytic amounts (the Sharpless method).The Se02 is the actual reagent the peroxide... 

A third variant of a metal-catalyzed enantioselective Baeyer-Villiger oxidation of cyclobutanones was reported by Lopp [30]. Up to 75% ee was achieved using the system for the epoxidation of allylic alcohols developed by Sharpless, i.e., Ti(Oi-Pr)4, chiral diethyl tartrate, and ferf-butyl hydroperoxide (Eq. 6). 

Sharpless epoxidation (Chapter 14 Lagniappe) A method for enantioselective synthesis of a chiral epoxide by treatment of an allylic alcohol with ferf-butyl hydroperoxide, (CHa)3C—OOH, in the presence of titanium tetraisopropoxide and diethyl tartrate. 

The first such process is a variant of the oxacyclo-propanation reaction discussed in Section 12-10, as applied specifically to 2-propenyl (allylic) alcohols. However, instead of a peroxycarboxylic acid, the reagent is ferf-butyl hydroperoxide in the presence of titanium (TV) isopropoxide ( Sharpless epoxidation ), the function of the chiral auxiliary being assumed by tartaric acid diethyl ester (Real Life 5-3). The naturally occurring (-l-)-[2/ ,3/ ]-diethyl tartrate and its nonnatural (—)-(25,35) mirror image are both commercial products. One delivers oxygen to one face of the double bond, the other to the opposite face, as shown below, giving either enantiomer of the oxacyclopropane product with high enantiomer excess (Section 5-2). 

In 1980, Sharpless and co-workers reported on the first practical asymmetric epoxidation of allylic alcohols using titanium-tartrate complexes in combination with ferf-butyl hydroperoxide (TBHP) as an oxidant." The procedure was later improved by the addition of 3-A or 4-A molecular sieves to the reaction mixmre, and under the optimal conditions the reaction can be performed with a catalytic amount of titanium catalysts prepared from Ti(0-f-Pr)4 and L or D-diethyltartrate (DET) or diisopropyltartrate (DIPT) to provide chiral epoxides in optical purities typically greater than 90% ee (Scheme 35.1). 

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