Direct organocatalytic asymmetric a-oxidation of ketones with iodosobenzene and N-sulfonyloxaziridines Magnus Engqvist, Jesu ´ s Casas, Henrik Sunde ´n, Ismail Ibrahem and Armando Co ´ rdova * Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden Received 25 October 2004; revised 17 January 2005; accepted 26 January 2005 Abstract—The novel, direct amino acid-catalyzed a-oxidation of ketones with iodosobenzene and N-sulfonyloxaziridines is pre- sented. A screen of several synthetically common oxidants revealed that iodosobenzene and N-sulfonyloxaziridines act as electro- philes in the direct organocatalytic asymmetric a-hydroxylation of ketones. The direct proline-catalyzed asymmetric a-oxidation of ketones with iodosobenzene yielded the corresponding a-hydroxylated ketones with up to 77% ee. Furthermore, several amino acid derivatives catalyze the stereoselective a-oxidation of ketones with N-sulfonyloxaziridines. For example, the direct diamine-cata- lyzed enantioselective a-hydroxylation of ketones with N-sulfonyloxaziridines furnished the corresponding a-hydroxylated products in moderate yield with up to 63% ee. Ó 2005 Elsevier Ltd. All rights reserved. One of the ultimate goals and challenges in chemistry is to develop stereoselective transformations for the crea- tion of optically active functional molecules from simple readily available starting materials. There are several methods for the preparation of enantiomerically pure compounds and among these asymmetric catalysis is a highly active research field. 1 Optically active a-hydroxy carbonyl moieties are com- monly found in numerous important natural products. 2 This has led to extensive research to find new diastereo- selective and enantioselective routes for their syntheses. 3 One way of preparing these compounds is by asym- metric a-hydroxylation of enolates employing chiral auxiliaries or substrates. 4 Recently, Momiyama and Yamomoto reported a more efficient catalytic system based on AgX/BINAP-complexes that mediate indirect a-oxidation of activated tin enolates with nitrosobenz- ene as the electrophile. 5 Organocatalysis has experienced a renaissance in organ- ic chemistry. 6 In this context, we and other researchers have reported that amino acids and their derivatives cata- lyze the direct Yamamoto-type a-aminoxylation reac- tion with excellent stereoselectivities. 7 These initial reports by Zhong, 7c MacMillan and co-workers, 7d Hay- ashi and co-workers 7e–g and us 7a,b were later followed up by the excellent studies of Yamamoto, 8 Blackmond and others. 9 Furthermore, we recently demonstrated that amino acids catalyze the biomimetic asymmetric aerobic a-oxidation of aldehydes and ketones. 10 Based on this research and our interest in amino acid-catalyzed asymmetric reactions, 11 we became interested in whether other oxidants could be employed in transformations with catalytically generated chiral enamines. Herein, we disclose the first examples of direct organocatalytic a-oxidation of ketones with iodosobenzene and N-sulfon- yloxaziridines yielding a-hydroxylated ketones and diols with up to 77% ee. In an initial screen of different oxidants for the a-oxida- tion of cyclohexanone 1a in the presence of a catalytic amount of L-proline (20 mol %), we found that iodoso- benzene (PhIO) and trans-2-(p-methylphenylsulfonyl)- 3-phenyloxaziridine 3 furnished the corresponding a- hydroxylated ketone 2a in 27% and 44% yields with 67% and 29% eeÕs, respectively. 12 On standing the a- hydroxy ketone 2a dimerized and oligomerized and was therefore reduced in situ with excess NaBH 4 to the corresponding diol 4a (Eq. 1). Encouraged by these preliminary results we carried out a catalyst and solvent screen on the direct asymmetric 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.01.167 * Corresponding author. Tel.: +46 8 162479; fax: +46 8 154908; e-mail addresses: acordova@organ.su.se; acordova1a@netscape.net Tetrahedron Letters 46 (2005) 2053–2057 Tetrahedron Letters