1366 SHORT PAPER Synthesis 2000, No. 10, 1366–1368 ISSN 0039-7881 © Thieme Stuttgart · New York Synthesis of Cycloocta-3,5-dien-1-ol and Cycloocta-3,5-dien-1-one: SeO 2 /O 2 Oxidation of Dienes Elena S. Koltun, Steven R. Kass* Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA Fax +1(612)6267541; E-mail: kass@chem.umn.edu Received 2 February 2000; revised 20 April 2000 Abstract: A useful synthesis of cycloocta-3,5-dien-1-ol was devel- oped starting from cycloocta-1,3-diene. Oxidation of the diene with selenium oxide in refluxing acetic anhydride affords the homoallyl- ic and allylic acetates in a 19:1 ratio and a 36% overall yield when O 2 is bubbled through the reaction mixture. Subsequent reduction with LAH affords the homoallylic alcohol (95%), which can be readily oxidized via TPAP/N-MMO (73%) to the corresponding non-conjugated dienone. This route represents the most efficient method for the preparation of cycloocta-3,5-dien-1-ol and cyclooc- ta-3,5-dien-1-one reported to date, and may provide a general ap- proach to the synthesis of homoallylic alcohols and non-conjugated enones. Keywords: selenium oxide, oxygen, homoallylic alcohol, non-con- jugated enone, oxidation Synthesis of cycloocta-3,5-dien-1-ol (1) has been attempt- ed several times via reduction of vinyl epoxides or seleni- um oxide oxidation of alkenes or dienes. 1-7 These methods result in mixtures of allylic and homoallylic products typically with the latter as the minor component. Even though cycloocta-3,5-dien-1-ol (1) and cycloocta- 2,4-dien-1-ol (2) can be separated via column chromatog- raphy on small scale, it is almost impossible to separate large amounts by distillation. Therefore, we developed an efficient procedure for the preparation of cycloocta-3,5- dien-1-ol (1) in two steps from an inexpensive starting material, cycloocta-1,3-diene. Hanold and Meier reported the synthesis of 1 via oxida- tion of cycloocta-1,3-diene with selenium oxide in reflux- ing acetic anhydride followed by reduction of the resulting acetates with lithium aluminum hydride (LiAlH 4 ). 1 This reaction sequence gave a mixture of prod- ucts, cycloocta-3,5-dien-1-ol (1), cycloocta-2,4-dien-1-ol (2), and cyclooct-3-en-1-one (6) in 7.5:1.5:1 ratio, respec- tively (Scheme 1). 8 In an attempt to prepare gram quantities of homoallylic al- cohol 1, we investigated the effect of oxygen on the prod- uct ratio in the selenium oxide and acetic anhydride oxidation of cycloocta-1,3-diene. As it turns out, the prod- uct ratio changes with the amount of oxygen in the reac- tion mixture as shown in the Table. When the reaction is carried out under nitrogen, the allylic alcohol 2 is the ma- jor product. When we reproduced the literature conditions and carried out the oxidation under air, the LiAlH 4 reduc- tion yielded 1 and 2 in a 2.5: 1 ratio, respectively. To in- crease the concentration of oxygen in the reaction mixture, air was bubbled through the refluxing acetic an- hydride solution and after the subsequent reduction, the ratio of the products was 5.5:1, respectively. 9 The propor- tion of homoallylic alcohol 1 was significantly improved when oxygen was bubbled through the reaction mixture. Only two isomers, 1 and 2, were isolated and they were obtained in a 19:1 ratio, respectively (Scheme 2). There- fore, a SeO 2 /O 2 combination allows homoallylic alcohol 1 to be prepared from an inexpensive starting material, cy- cloocta-1,3-diene, in 33% overall yield and 95% purity. Homoallylic alcohol 1 was oxidized with tetrapropylam- monium perruthenate (TPAP)/4-methylmorpholine N-ox- ide (N-MMO) without migration of the double bonds into conjugation with the ketone (Scheme 2). 10 This method, therefore, could be an efficient way for the synthesis of b,g-unsaturated alcohols and ketones. Further investiga- tions into the generality of the SeO 2 /O 2 /Ac 2 O reaction conditions for the synthesis of a variety of homoallylic al- cohols and b,g-unsaturated ketones is currently underway. Cycloocta-3,5-dien-1-ol (1) For a 10 min period O 2 was bubbled through a vigorously stirred mixture (with a teflon coated stirring bar) of cycloocta-1,3-diene (11.3 g, 0.1 mol), SeO 2 (11.3 g, 0.1 mol) and Ac 2 O (75 mL). After the solution was saturated with O 2 , it was heated to reflux for 12 h. O 2 was bubbled through the reaction mixture over this entire period and the mixture changed color from red to deep black within 30 min; if any red color persists it is important to promptly raise the temperature of the heating mantle or oil bath, otherwise a significant amount of the allylic product forms. The mixture was allowed to cool to r.t. and filtered through a plug of silica gel. The residue was rinsed with Et 2 O (150 mL) and the combined organic layers were washed with H 2 O (2 × 50 mL), 2 N NaOH (50 mL) and brine (100 mL). The resulting solution was dried (MgSO 4 ) and concen- trated under reduced pressure. Vacuum distillation (0.3 Torr) af- forded acetates 3 and 4 in a 95:5 ratio, respectively (6 g, 36%); bp 54-58 °C (Lit. 1 bp 63-65 °C/2 Torr). The resulting acetate mixture (5 g, 0.03 mol) was dissolved in Et 2 O (50 mL) and a 1 M LiAlH 4 (0.04 mol, 40 mL) solution in THF was slowly added. The mixture was refluxed (36-40 °C) under N 2 for 2 h and cooled to 0 °C. To the resulting solution was added slowly sat. NH 4 Cl solution (20 mL) OH HO 1 2