DIRHODIUM CAPROLACTAMATE CATALYZED OXIDATIONS BY TERT-BUTYL HYDROPEROXIDE. FROM MECHANISMS TO NEW METHODOLOGIES
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Dirhodium caprolactamate, Rh2(cap)4, is a very efficient catalyst for the generation of the tert-butylperoxy radical from tert-butyl hydroperoxide, and the tert-butylperoxy radical is a highly effective oxidant for phenols and anilines. These reactions are performed with 70% aqueous tert-butyl hydroperoxide using dirhodium caprolactamate in amounts as low as 0.01 mol % in toluene and chlorobenzene to oxidize para-substituted phenols to 4-(tert-butyldioxy)cyclohexadienones. Electron rich and electron poor phenolic substrates undergo selective oxidation in good to excellent yields, but steric influences from bulky para substituents force oxidation onto the ortho position resulting in ortho-quinones. Comparative results with RuCl2(PPh3)3 and CuI are provided, and mechanistic comparisons are made between these catalysts that are based on diastereoselectivity (reactions with estrone), regioselectivity (reactions with p-tert-butylphenol) and chemoselectivity in the formation of 4-(tert-
butyldioxy)cyclohexadienones. The data obtained are consistent with hydrogen atom abstraction by the tert-butylperoxy radical followed by radical combination between the phenoxy radical and the tert-butylperoxy radical. Under similar reaction conditions para-substituted anilines are oxidized to nitroarenes in good yield.
An efficient one-pot tandem sequence forming heterocycles is developed. The method consists of an efficient phenol oxidation with inexpensive T-HYDRO catalyzed by dirhodium caprolactamate followed by Bronsted acid promoted cyclization. Substrate scope includes uses of L-tyrosine ester and dipeptide derivatives. Application of chiral phosphoric acids for asymmetric cyclization is discussed. Previously unreported peroxide cleavage with TiCl4 enables a rapid synthesis of cleroindidin F.
A general mechanism is proposed for transition metal catalyzed oxidative Mannich reactions of N-methylanilines with tert-butyl hydroperoxide (TBHP) as an oxidant. Kinetic data and isotope labeling of the N-methyl group suggest a rapid equilibrium between an iminum ion and solvent or TBHP preceding Mannich addition. Linear free-energy relationship (LFER) analysis, kinetic and product isotope effects, and utilization of radical clock substituents establish tert-butylperoxy radicals as an oxidant in dirhodium(II) caprolactamate [Rh2(cap)4] catalyzed oxidations of N,N-dialkylaniline by TBHP. Isotope effects measured for various transition metal salts reveal a general role of alternative catalysts as initiators of TBHP decomposition in N,N-dialkylaniline oxidations. New mechanistic insights led the development of the novel FeCl3 catalyzed oxidative Mannich reaction.