DOI: 10.1021/jo902637k Published on Web 02/08/2010 J. Org. Chem. 2010, 75, 1807–1810 1807 r 2010 American Chemical Society pubs.acs.org/joc An Effective Method for Allylic Oxidation of Δ 5 -Steroids Using tert-Butyl Hydroperoxide Yuancheng Li, Xianghong Wu, Tae Bum Lee, Eleanor K. Isbell, Edward J. Parish, and Anne E. V. Gorden* Department of Chemistry and Biochemistry, College of Science and Mathematics, Auburn Univeristy, Auburn, Alabama 36849-5319 gordeae@auburn.edu Received December 27, 2009 An allylic oxidation method for Δ 5 -steroids using TBHP as oxidant with a 2-quinoxalinol salen Cu(II) complex as catalyst is reported. A variety of Δ 5 -steroidal substrates are selectively oxidized to the corresponding enones. Excellent yields are achieved (up to 99% under optimized conditions) while significantly reducing reaction times required as compared to other current methods. Because of the biological and physiological properties of their 7-keto-Δ 5 -steroid oxidation products, Δ 5 -steroids have attracted attention as highly useful synthetic building blocks. 1-10 Easy access to the 7-keto-Δ 5 -steroids can be achieved via allylic oxidation of Δ 5 -steroids. Although a variety of chromium(VI) compounds have been used in the synthetic modifications of steroids, 4,11-15 complications in applying these methods remain because of the harsh reaction conditions required and difficult workup and/or purification procedures. In addition, the accumulations of chromic acid or chromium salt wastes that are the side products of these reactions are of great environmental concern. 16 To complete such modifications in a more environmentally friendly yet still efficacious manner, many other metal complexes/salts have been employed, such as sodium chlorite, 17 copper iodide, 5 dirhodium caprolactamate, 18 ruthenium trichloride, 19 bismuth salt, 20 cobalt acetate, 21 palladium(II) salts, 22 and manganese- (III) acetate; 23 however, numerous limitations remain. All of the available methods must strike a balance between good yields and functional group compatibility while continuing to suffer from long reaction time requirements. Oxidations using manganese(III) acetate and dirhodium caprolactamate as catalysts are two more recent representative examples of the current methods. 17,21 The use of manganese(III) acetate allowed for excellent yields in Δ 5 -steroidal oxidation under ambient temperature when tert-butyl hydroperoxide was used as oxidant. The reaction times were reduced remarkably when the reaction mixture was heated, but with a loss in yield. This method also does not exhibit compatibility with sensitive functionalities near allylic sites (e.g., hydroxyl group). 21 The use of the dirhodium caprolactamates as catalysts in such an allylic oxidation showed a wide tolerance for a variety of functional groups, and yet it also had decreased yields. 17 Previously, we have reported a new catalytic system that consists of 2-quinoxalinol salen copper(II) complex 2 as a catalyst using tert-butyl hydroperoxide (TBHP) as an oxidant. 24 The 2-quinoxalinol salen copper(II) system was demonstrated (1) Guardiola, F.; Codony, R.; Addis, P. B.; Rafecas, M.; Boatella, J. Food Chem. Toxicol. 1996, 34, 193–211. (2) Schroepfer, G. J. J. Physiol. Rev. 2000, 80, 361–544. (3) Guardiola, F.; Dutta, P. C.; Codony, R.; Savage, G. P. Cholesterol and Phytosterol Oxidation Products: Analysis, Occurrence, and Biological Effects; AOCS Press: Champaign, IL, 2002. (4) Parish, E. J.; Kizito, S. A.; Qiu, Z. Lipids 2004, 39, 801–804. (5) Arsenou, E. 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