Selective Oxidations in the Synthesis of Complex Natural ent-Kauranes and ent-Beyeranes

Abstract

Syntheses of two natural products derived from the ent-kaurene kaurenoic acid are described for the first time using regio-and diastereoselective oxidations. Palladium-and manganese-mediated oxidations were used to accomplish the syntheses of two ent-beyerane metabolites. The use of the White−Gormisky−Zhao catalyst Mn(CF 3 -PDP) enabled the first application of a nondirected metal-catalyzed oxidation in an unactivated C−H bond in a total synthesis.

Transition Metal-Catalyzed Direct Stereoselective Oxygenations of C(sp3)–H Groups

“…Using manganese based catalyst ( R , R )- 30 , de Lucca with co-workers developed the procedure for remote hydroxylation of ent -beyeran-19-oic acid derivative IX (Figure ). The reaction preferentially occurred at the equatorial C2β-site . While at 0 °C and under 10-fold oxidant excess conditions, C2-ketone was formed as the major product; reducing the temperature to −45 °C and limiting H 2 O 2 excess to 2.0 equiv furnished 38% yield of the C2β-hydroxy derivative, an intermediate of total synthesis of ent -beyerane metabolites …”

“…The reaction preferentially occurred at the equatorial C2β-site . While at 0 °C and under 10-fold oxidant excess conditions, C2-ketone was formed as the major product; reducing the temperature to −45 °C and limiting H 2 O 2 excess to 2.0 equiv furnished 38% yield of the C2β-hydroxy derivative, an intermediate of total synthesis of ent -beyerane metabolites …”

“…The reaction preferentially occurred at the equatorial C2β-site. 116 While at 0 Scheme 4. Alternative Mechanistic Scenarios Leading to γ-Lactones Figure 19.…”

“…Structures of non-heme iron and manganese complexes, capable of conducting C−H hydroxylation of complex substrates. 116 We reported the effect of catalyst absolute chirality on the selectivity of oxygenation of estrone acetate: in the presence of Mn complexes of the type 20 (Figure 12), the reaction occurred preferentially at either C9 (α-hydroxylation) or C6 (ketonization) positions (Figure 21). 104 The catalytic efficiency of the Mn based catalysts was remarkably high, such that 0.3 mol % catalyst loadings were sufficient to complete the reaction within a few hours at −30 °C.…”

Metal-Catalyzed C–H Bond Oxidation in the Total Synthesis of Natural and Unnatural Products

“…64 De Lucca and co-workers applied the Sanford protocol to synthesize this diterpenoid (Scheme 29). 65 The oxime 107 was treated with Pd(OAc)2 and PhI(OAc)2, furnishing the acetoxylated product 108 in 52% yield and 26% of recovered starting material. Compounds 112 and 113 represent examples of lactonizations in good selectivities.…”