Chiral epoxidizing agent

Kinetic resolution.l33 Since enantiomers react with chiral compounds at different rates, it is sometimes possible to effect a partial separation by stopping the reaction before completion. This method is very similar to the asymmetric syntheses discussed on p. 102. An important application of this method is the resolution of racemic alkenes by treatment with optically active diisopinocampheylborane,134 since alkenes do not easily lend themselves to conversion to diastereomers if no other functional groups are present. Another example is the resolution of allylic alcohols such as 45 with one enantiomer of a chiral epoxidizing agent (see 5-36).135 In the case of 45 the discrimination was extreme. One enantiomer was converted to the epoxide and the other was not, the rate ratio (hence the selectivity factor)... 

Optically active diisopinocamphenylborane can be used to resolve racemic olefins. The reagent adds to one enantiomer, and the other is unchanged. Optical purities on the order of 37-65% are possible. Chiral ally lie alcohols can be resolved with chiral epoxidizing agents derived from tartrate complexes of titanium. One enantiomer is epoxidized and the other is not. Thus, die two alcohol enantiomers can be separated, one as the unsaturated alcohol and one as the epoxy alcohol. Use of die other tartrate isomer reverses die stereoselectivity. Selectivities on die order of >100 are possible with this method. As in any kinetic resolution, however, only one enantiomer can be recovered. The other is converted to a different chiral product. 

Two chiral epoxidizing agents for enones are brucine A-oxide and cyclo(L-Pro-L-Pro) hydroperoxide, but the latter reagent produces epoxides of low ee. 

In cases where Noyori s reagent (see p. 102f.) and other enantioselective reducing agents are not successful, (+)- or (—)-chlorodiisopinocampheylborane (Ipc BCl) may help. This reagent reduces prochiral aryl and tert-alkyl ketones with exceptionally high enantiomeric excesses (J. Chandrasekharan, 1985 H.C. Brown, 1986). The initially formed boron moiety is usually removed hy precipitation with diethanolamine. Ipc2BCl has, for example, been applied to synthesize polymer-supported chiral epoxides with 90% e.e. from Merrifield resins (T. Antonsson, 1989). 

The use of alkylhydroperoxides as epoxidizing agents for allylic alcohols under catalytic conditions was soon expanded into enantioselective epoxidation with use of the more mild titanium alkoxides in the presence of chiral tartaric esters116. As concerns the epoxidation of functionalized dienes, these now so-called Sharpless conditions [Ti(OPr )4, dialkyl tartrate, TBHP] have been utilized to enantioselectively epoxidize 1,4-pentadiene-... 

It should be noted that although oxiranes (8) and (9) are chiral, this epoxidation methodology gives the racemate since no chiral inducing agent is present. 

The general approach has been used to access a wide variety of chiral epoxides. One example is in the synthesis of (3-adrenergic blocking agents (Scheme 9.12).114... 

The use of chiral peracids was pioneered by Henbest1 who produced epoxides with an enantiomeric excess of 5% using ( + )-monoperoxycamphoric acid (1). The acid used was shown to be a mixture of isomers2 and later work improved enantiomeric excess in these reactions to 15% by using more highly purified epoxidizing agent. 

Epoxidations. A mixture of Oxone and an iminium salt derived from pyrrolidine is an effective epoxidizing agent. An imino group can also be exploited for directing epoxidation of a proximal double bond.- The oxodiazepinium salt I- and 4-oxothiane-S,S-dioxide are also general and efficient catalysts. A popular approach to asymmetric epoxidation of alkenes is based on generating dioxiranes in situ from chiral ketones and Oxone . ... 

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