Tetrahedron Lcuem, VoL31. No.36. pp5235-5236.1990 Rited in Great Britain 0@40-4039/90 $3.00 + .oa Pcrgamon Ross plc zyxwvutsrqp USE OF DIMETHYLDIOXIRANE IN THE PREPARATION OF HIGHLY REACTIVE COMPOUNDS: FIRST DIRECT EPOXIDATION OF PRECOCENES Jordi Bujons, Francisco Camps and Angel Messeguer* Dpt. of Biological Organic Chemistry, CID (CSIC). J. Girona. 18. 08034 Barcelona, Spain. Summary: Natural precocenes and related analogues react with dimethyldioxirane to give the corresponding 3.4-epoxy derivatives in very high yields. This procedure constitutes the first direct preparation of these highly reactive compounds. The unstability and high reactivity exhibited by 3.4-epoxyprecocenes (2). the bioactivated intermediates postulated as responsible for the cytotoxic activity of precocenes (1) in insects t and in mammalian tissues 2, have attracted the interest of research groups working not only in insecticides but also in areas connected with toxicologic and xenobiochemical problems. However. the availability of these compounds has been heretofore difficult due to their troublesome synthesis and isolation. To the best of our knowledge, all efforts carried out to prepare 3,4-epoxy derivatives of activated precocenes lc-f by direct epoxidation have been unsuccesful. since a concomitant opening ,of the epoxide occurred under the reaction conditions. The only synthetic procedure which afforded the expected 3,4- epoxyprecocenes was an indirect one involving the dehydrohalogenation of the corresponding bromohydrins 3-s. However, with exception of 3,4-epoxyprecocene I (2~) 3, which could be crystallized, in all other cases the unstability of the epoxides precluded their final purification. Consequently, epoxide reactivity can be modified by impurities present in the crude reaction mixture 6. In that context, a recent report on the use of dimethyldioxirane ’ for the succesful epoxidation of aflatoxin B, ( AFB t) ” suggested us to assay this reagent to overcome the above drawbacks. In the present communication, our results on the use of dimethyldioxirane for performing the first direct epoxidation of precocenes are presented. In cases of non activated precocenes (la-b), reaction conditions reported for AFBt oxidation 7c were appropriate to obtain the corresponding epoxides in good, reproducible yields. However, when activated substrates such as precocenes I and If (lc and Id, respectively), and analogues le 6 and If 5 were used, more drastic precautions had to be taken to avoid the presence of any acid or protic solvent in the reaction medium, which gives an idea about the extreme reactivity of these epoxides. Accordingly, only thoroughly dried dimethyldioxirane acetone solution and acetonitrile as cosolvent 9 at low temperatures (-40 “C) led to the complete conversion of precocenes into their corresponding 3.4-epoxy derivatives, which were obtained in good reproducible yields (Table) lo. 5235