2.3- Epoxy alcohols Subject

The construction of key intermediate 18 can be conducted along similar lines. Sharpless asymmetric epoxidation of allylic alcohol 22 using (+)-DET furnishes epoxy alcohol 52b (Scheme 11). Subjection of the latter substance to the same six-step reaction sequence as that leading to 54a provides allylic alcohol 54b and sets the stage for a second SAE reaction. With (+)-DET as the... 

Several other allylic alcohols with primary C-2 substituents have been epoxidized with very good results (entries 7-10, 14). Epoxy alcohols have been obtained with 95-96% ee and, when the catalytic version of the reaction is used, as in entry 10, the yield is excellent. When the C-2 substituent is more highly branched, as in entries 11-13, there may be some interference with high enantiofacial selectivity by the bulky group, because the enantioselectivity in two cases (entries 11 and 12) is 86%. Another example that supports this possibility of steric interference to selective epoxidation is summarized in Eq. 6A.3a [39]. In this case the optically active allylic alcohol 12, (3/ )-3,7-dimethyl-2-methylene-6-penten-l-ol, was subjected to epoxidation with both antipodes of the Ti-tartrate catalyst. With (+)-DIPT, enantiofacial selectivity was 96 4... 

A limited number of allylic alcohols of the (2,3Z)-disubstituted type have been subjected to asymmetric epoxidation. With one exception, the C-2 substituent in these substrates has been a methyl group, the exception being a f-butyl group [38]. The (3Z)-substituents have been more varied, as illustrated by structures 61-64, which show the epoxy alcohols derived from the corresponding allylic alcohol substrates. 

When the allylic alcohol is the desired product of the kinetic resolution process, the accompanying epoxy alcohol also may be converted to the desired allylic alcohol by the two-step sequence shown in Scheme 6A. 1. The epoxy alcohol, after separation from the allyl alcohol, is mesylated and then subjected to reaction with sodium telluride, which effects the transformation of epoxy mesylate to the allylic alcohol with inversion at the asymmetric carbinol center [ 115e]. Preliminary results suggest that the rearrangement follows this pathway only when the epoxy alcohol is unsubstituted at the 3-position. 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

In this case, the optically active allylic alcohol (12) was subjected to epoxidation with both antipodes of the titanium tartrate catalyst. With (-h)-DIPT enantiofacial selectivity was 96 4 ( matched pair ), but with (-)-DIPT selectivity fell to only 1 3 ( mismatched pair ), a further indication that a sec-ondaiy C-2 substituent can perturb the fit of the substrate to the active catalyst species. In the epoxidation of the allylic alcohol shown in elation (4), the epoxy alcohol is obtained in 96% yield and with a 14 1 ratio of enantiofacial selectivity. An interesting alternate route to the epoxide of entry 12 (Table 3) has been described, in which 2-r-butylpropene is first converted to an allylic hydroperoxide via photooxyge-nation and then, in the presence of the titanium tartrate catalyst, undergoes asymmetric epoxidation (79%... 

As before, the hydroxy group of this epoxy alcohol was subjected to a Mitsonobu esterification and subsequent cleavage of the resulting benzoate ester 14 to afford epoxy alcohol 15, with the desired relative stereochemistry, in 87 % yield over two steps. The free hydroxy group was protected, as previously, with a benzyl group in 96 % yield. 

Another modification of Route B requires enantioselective reduction of ketones (E)-27 or stereoselective carbon-carbon bond formation at C-1 of (E)-27 (R = H) with appropriate organometallic species in the presence of chiral additives, both of which successfully supply the optically active (E)-26. The resulting chiral allylic alcohols (E)-26 are subjected to hydrogen bond-directed epoxidation with mCPBA, leading to the diastereoselective formation of syn-epoxy alcohols. In conplementary fashion, antz-selective epoxidation is possible using the Sharpless protocol. ... 

Another protected epoxy-alcohol, rac-2-methylglycidyl benzyl etiier, has been the subject of numerous investigations. Two types of EHs proved to be useful those from various Rhodococcus strains [148-151] and the one from Bacillus subtilis [6,152]. 

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