1166 Russian Chemical Bulletin, Vol. 47, No. 6, June, 1998 Ring-expansion reaction of 1 -hydroperoxy- 16-oxabicyci o [ 10.4.0 ] hexadecane catalyzed by copper ions: use in the synthesis of 15-pentadecanolide Yu. N. Ogibin,* A. O. Terent'ev, and G. L Nikishin 3[. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 117913 Moscow, Russian Federation. Fax: +7 (095) 135 5328. E-mail: ogibin@ioc.ac.ru A catalytic procedure has been developed for the synthesis of 15-pentadecanolide (1) from readily available l-hydmperoxy-16-oxabicyclo[10.4.0lhexadecane (2). The method is based on the reaction of hydroperoxide 2 with copper acetate (0.15~5 mol.%). Ring expansion occurred as a result of generation of tertiary bieyclohexadecyloxyl radicals 4 from hydroperoxide Z under the action of Cu I ions, I]-scission of the radicals accompanied by regioselective cleavage of the bridge bond to form macrocyclic C-centered radicals 5, and their oxidation by Cu tl ions to (/~-11- and (E)-12-pemadecen-15-olides (6). The products obtained were converted into 15-pentadecanolide by subsequent catalytic hydrogenation over a Pd catalyst in a yield of more than 9096 with respect to hydroperoxide 2. Key words: I-hydroperoxy-16-oxabicyclo[10.4.0]hexadecane, ring expansion, (E)-I 1- and (L0-12-pentadecen-15-olides, 15-pentadecanolide, cyclododecanone, allyl alcohol, 2-(3-hydroxypropyl)cyclododecanone, 13-oxabicyclo[10.4.01hexadec-l(12)-ene, hydrogena- tion. 15-Pentadecanolide (1) possesses a unique musk- amber odor and is capable of fixing odors of other aromatic principles due to which 1 is widely used in production of perfumes and cosmetics. A large number of various multistage procedures for the synthesis of this maerocyclic lactone are known. 1-18 However, only one of these procedures is used for producing this lactone. This method involves ring expansion of l-hydroperoxy- 16-oxabicyclo[10.4.01hexadecane (2) as the key stage. ./ Compound 2 is prepared by the addition of hydrogen peroxide to 13-oxabicyclo[ 10.4.01hexadec- l(12)-ene (3). Compound 3 is synthesized according to different pro- cedures from cyclododecanone. 7~,lg-zt Four procedures for the initiation of ring expansion of hydroperoxide 2 a,ad its analogs are known, namely, boiling in xylene, 7b photoirradiation, 7b the reaction with a threefold excess of a mixture of sodium sulfite and sodium bisulfite in a solution of equal volumes of chlo- roform and isopropyl alcohol, 7 and the reaction with a one-and-a-half-fold excess of a,a equimolar mixture of copper(t0 acetate and iron(H) sulfate heptahydrate in methanol.Z2, z3 We carried out this reaction with the use of copper acetate as a catalyst. Ring expansion of hydroperoxide 2 occurred as a result of generation of tertiary bicyclo- hexadecyloxyl radicals (4) from hydroperoxide 2 under the action of copper ions, I~-scission of the radicals accompanied by regioselective cleavage of the bridge bond to form macrocyclic radicals (5), and their oxida- tion by Cu II ions to (E)-II- and (E)-12-pentadecen- 15-olides (6). The products obtained were convened into 15-pentadecanolide (1) by subsequent catalytic hy- drogenation over a Pd catalyst in a yield of more than 90% with respect to hydroperoxide 2 (Scheme 1). Tile initial hydroperoxide 2 was prepared from cyclododecanone (7) and allyl alcohol via 2-(3-hydroxy- propyl)cyclododecane (8) and 13-oxabicyc- 1o[ 10.4.01hexadec- 1(12)-ene (3) according to Scheme 2. Ring expansion of hydroperoxide 2 was carried out in the presence of CuP(At) 2 (0.0015--0.07 equiv.) by adding a suspension of hydroperoxide 2 in an organic solvent to an intensively stirred boiling solution or sus- pension of copper acetate in the same solvent. The reaction mixture was boiled with stirring until decompo- sition of hydroperoxide was completed. When 0.05 equivalents of copper acetate (this amount is optimum) were used, decomposition was completed in from 2 to 40 h depending on the nature of the solvent and the boiling temperature of the reaction mixture (Table I). The yields of pentadecenolides 6 were up to 96.5%. 4-Methylpentan-2-one is the best solvent for the trans- formation of hydroperoxide 2 into compounds 6 as regards the selectivity of the reaction and the quality of the target product obtained by catalytic hydrogenation of 6. Buta,~-2-one is only insignificantly inferior to 4-methylpeqtatl-2-one. Whe,~ aromatic hydrocarbons Translated flom Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 6, pp. 1197--1200, Jtmc, 1998. 1066-5285/q8/4706-1166 $20.00 ~ 1998 Plenttnl Publishit~g Corporation