Catalytic Asymmetric <i>cis</i> -Dihydroxylation of Quinones Enabled by a Functional Mimic of Rieske Dioxygenases

The development of efficient and practical catalytic asymmetric cis -dihydroxylation reactions using earth-abundant metal catalysts remains a major challenge; the cis -dihydroxylation of 1,4-quinones represents a vital gateway to enantioenriched cis -1,2-diols, which are privileged scaffolds for bioactive natural products and pharmaceuticals. Inspired by the asymmetric cis -dihydroxylation of aromatic and olefinic C═C bonds catalyzed by Rieske dioxygenases, we present a biomimetic strategy for the asymmetric cis -dihydroxylation of 1,4-quinones. Herein, we report an inexpensive and readily accessible nonheme manganese complex, supported by a tetradentate aminopyridine ligand featuring a rigid chiral diamine backbone and a sterically bulky triisopropylsilyl group, for the cis -dihydroxylation of 1,4-quinones by hydrogen peroxide and alkyl hydroperoxides; it is noted that this study reports the first example of using alkyl hydroperoxides as a terminal oxidant in cis -dihydroxylation reactions. Various 1,4-quinones were efficiently oxidized to cis -1,2-diols in synthetically useful yields with excellent chemo-, regio-, and enantioselectivity (up to 99% ee), along with complete diastereoselectivity. Mechanistic evidence from experimental and computational studies supports a highly electrophilic manganese(V)-oxo-hydroxo species as the active cis -dihydroxylating intermediate, although the formation mechanism of the high-valent manganese-oxo intermediate is different depending on the hydroperoxide oxidants. Moreover, a two-step mechanism is proposed for the manganese(V)-oxo-hydroxo-mediated asymmetric cis -dihydroxylation, such as the Re -face selective oxo attack on the less hindered C═C bond, followed by OH-rebound, with stereochemistry dictated by the initial oxo attack. Thus, this study delineates the first biomimetic oxidation strategy enabling asymmetric cis -dihydroxylation of 1,4-quinones mediated by a high-valent manganese-oxo species generated in the reactions of hydrogen peroxide and alkyl hydroperoxides.