CHIRAL HETEROARYLOXYMETHYLOXIRANES

Several approaches to the synthesis of chiral heteroaryloxymethyloxiranes have been developed. The most direct method involves the reaction of an aromatic moiety bearing a readily displaceable leaving group with the sodium salt of chiral glycidol. An alternative procedure utilizes the sodium salt of chiral glycerol 1, 2-acetonide in the displacement of a leaving group from an aromatic system to give the 3-(aryloxy)-1, 2-propanediol acetonide. Controlled acid catalyzed deblocking of the acetonide yields chiral 3-(aryloxy)-1, 2-propanediol. More vigorous hydrolytic conditions lead to a rearrangement of the diol, which ultimately produces racemization. A detailed study regarding the mechanism of this rearrangement is presented. The chiral 3-(aryloxy)-1, 2-propanediol generated under the mild hydrolytic conditions could be converted through the monomesylate to the chiral oxirane. Finally, an example of the preparation of chiral aryloxymethyloxiranes from the corresponding chiral 3-amino-1-(aryloxy)-2-propanols is described. © 1979, American Chemical Society. All rights reserved.