Asymmetric epoxidation compatibility

TABLE 6A.1. Compatibility or Functional Groups with the Asymmetric Epoxidation Reaction... 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

Fortunately, a wide variety of functionality is compatible with the Ti-tartrate catalyst (see Table 6 A. 1), but the judicious placement of functional groups relative to the allylic alcohol can lead to further desirable reactions following epoxidation. For example, in 40, asymmetric epoxidation of the allylic alcohol is followed by intramolecular cyclization under the reaction conditions to give the tetrahydrofuran 41 [67]. Likewise, in the epoxidation of 42, cyclization of the intermediate epoxy alcohol occurs under the reaction conditions and leads to the cyclic urethane 43 [68]. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

The efficiency of kinetic resolution is even greater when there is a silicon or iodo substituent in the (3 )-position of the C-1 chiral allylic alcohols. The compatibility of silyl substituents with asymmetric epoxidation conditions was first shown by the conversion of (3 )-3-trimethylsilylallyl alcohol into (2/ ,3/ )-3-trimethylsilyloxiranemethanol in 60% yield with >95% and further exploited by the conversion of ( )-3-(triphenylsilyl)-2-[2,3- H2]propenol into (2 ,3/ )-3-triphenylsilyl[2,3- H2]oxirane-methanol in 96% yield and with 94% gg.io7b,i07c. pentyl group at C-1, the k,A for asymmetric... 

The allylic alcohol binds to the remaining axial coordination site where stereochemical and stereoelec-tronic effects dictate the conformation shown in Figure S. The structural model of catalyst, oxidant and substrate shown in Figure 5 illustrates a detailed version of the formalized rule presented in Figure 1. Ideally, all the observed stereochemistry of epoxy alcohol and kinetic resolution products can be rationalized according to the compatibility of their binding with the stereochemistry and stereoelectronic requirements imposed by this site. A transition state model for the asymmetric epoxidation complex has been calculated by a frontier orbital proach and is consistent with the formulation portrayed in Figure... 

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