Asymmetric Synthesis DOI: 10.1002/anie.200901039 Asymmetric Hydroxylative Phenol Dearomatization through In Situ Generation of Iodanes from Chiral Iodoarenes and m-CPBA** StØphane Quideau,* Gildas Lyvinec, MØlanie Marguerit, Katell Bathany, AurØlie Ozanne- Beaudenon, Thierry Buffeteau, Dominique Cavagnat, and Alain ChØnedØ The quest for chiral hypervalent iodine (iodane) reagents capable of promoting asymmetric induction in oxygenating reactions, such as the oxidation of sulfides into sulfoxides, the a-oxygenation of ketones, the dioxygenation of olefins, and the oxygenative dearomatization of phenols into cyclohexa- dienone derivatives, continues to challenge the organic chemistry community. [1] The best results reported so far are: a) the oxidation of methyl tert-butylsulfide (56 % ee) using a (+)-menthylated variant of the l 3 -iodane (i.e., iodine(III)) Koser reagent (A, Figure 1), [1a,c] and b) that of methyl p- tolylsulfide (29 % ee) using a chiral l 5 -iodane (i.e., iodine(V)) N-(2-iodylphenyl)acylamide (NIPA) reagent developed by Zhdankin and co-workers (B, Figure 1); [1d] c) the a-oxytosy- lation of propiophenone (40 % ee), and d) the dioxytosylation of styrene (65 % ee) using a chiral Koser-type reagent developed by Wirth and co-workers (C, Figure 1); [1f] and e) an intramolecular dearomatizing spirolactonization of a series of naphthol derivatives (78–86 % ee) using a chiral bis(l 3 -iodane) spirobiindane-based reagent recently devel- oped by Kita and co-workers (D, Figure 1). [1h, 15] Our own efforts toward the development of asymmetric phenol dearomatization reactions [2] and the efficacy of the l 5 - iodane 2-iodoxybenzoic acid (IBX) or its stabilized non- explosive version (SIBX) [3] in mediating hydroxylative phenol dearomatization (HPD) in a strictly ortho-selective manner led us to envisage the use of a chiral oxygenating iodane in this reaction. The HPD reaction is a powerful means for preparing, in one step, chiral 6-alkyl-6-hydroxycyclohexa-2,4- dienones from simple (achiral) 2-alkylphenols or related arenol variants. [4] These systems, trivially referred to as ortho- quinols, either constitute the structural core of some natural products or can serve as advanced intermediates in the synthesis of several others. [4, 5] Thus, having access to a chiral iodane reagent capable of enantioselectively installing a hydroxy group at an alkylated ortho position of a phenol would enable the reagent controlled preparation of ortho- quinols in a nonracemic form. Our first approach toward this objective was to generate IBX analogues having either a center or an axis of chirality as close as possible to the iodine center. The iodoarenes 1a–e and 2a–c were thus considered as chiral precursors of either six-membered-ring homologues of IBX or biaryl variants (Figure 2). Extensive efforts were spent on converting these iodoarenes (using either racemates or enantiomerically pure forms) into their corresponding l 5 -iodane iodoxy derivatives using various reagent systems known to achieve this type of Figure 1. Select examples of chiral l 3 - and l 5 -iodane reagents. Ts = p- toluenesulfonyl. Figure 2. Starting chiral iodoarenes and isolated iodanes. [*] Prof. S. Quideau, Dr. G. Lyvinec, M. Marguerit, K. Bathany, Dr. A. Ozanne-Beaudenon, Dr. T. Buffeteau, Dr. D. Cavagnat UniversitØ de Bordeaux Institut des Sciences MolØculaires (CNRS UMR 5255) Institut EuropØen de Chimie et Biologie 2 rue Robert Escarpit, 33607 Pessac Cedex (France) Fax: (+ 33) 5-4000-2215 E-mail: s.quideau@iecb.u-bordeaux.fr Dr. A. ChØnedØ Simafex, 17230 Marans (France) [**] We thank Simafex, the Association Nationale de la Recherche Technique (CIFRE Grants No. 457/2005 & 301/2002), and the Institut Universitaire de France for their financial support. m-CPBA = meta-chloroperoxybenzoic acid. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.200901039. Angewandte Chemie 4605 Angew. Chem. Int. Ed. 2009, 48, 4605 –4609  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim