Conventional homogeneous catalysis relies on one transition metal/ligand combination to promote all steps within a catalytic cycle. This approach is suboptimal when different steps within the cycle place different demands on the catalyst. Herein we report for the first time a serial ligand catalysis mechanism in which two different ligands interact sequentially with the metal to promote different product-forming steps of the same catalytic cycle. We recently reported sulfoxide-promoted, catalytic Pd(OAc) 2 / benzoquinone (BQ)/AcOH R-olefin allylic oxidation systems 1 that have the interesting feature of furnishing either predominantly linear or branched allylic acetates depending on whether DMSO or bissulfoxide ligands are used, respectively. 1a While investigating the bis-sulfoxide-promoted system, we discovered that 1 partially decomposes 2 under the reaction conditions to generate vinyl sulfoxide 2 (Table 1). We tested commercially available 2 and found that 10 mol % 2/Pd(OAc) 2 effectively promotes the oxidation reaction to furnish branched products with no decomposition. 1b,3 Reducing the equivalents of AcOH significantly improves regioselectivities (Table 1, entries 3a,b) by suppressing a background Pd(II)-mediated isomerization. 4 We now report a vinyl sulfoxidepromoted catalytic system for the mild, chemo-(R-versus internal olefins), and highly regioselective C-H oxidation of R-olefins to furnish allylic alkyl and aryl esters that proceeds via a mechanism in which two different ligands are responsible for promoting different steps in the catalytic cycle (Table 3). Mechanistic studies were carried out to establish the fundamental steps of this catalytic cycle and the role of vinyl sulfoxide 2 and BQ therein. When stoichiometric mixtures of 1-undecene, Pd(OAc) 2 , and 2 were heated and monitored by 1 H NMR, dimeric π-allylpalladium acetate complex A was observed in ca. 59% yield (eq 1). 5a-c When BQ was then added to this reaction mixture, formation of allylic acetate product was observed with yields and regioselectivities similar to those observed for the stoichiometric reaction run in the presence of BQ (eq 1, Table 1, entry 3h). In the absence of 2, with and without BQ, formation of complex A was not observed. These data are consistent with 2, and not BQ, acting as a ligand to effect Pd-mediated allylic C-H cleavage to likely form a monomeric π-allylpalladium intermediate that is detected in the form of dimeric complex A.

Carbohydrates from hydrocarbons: A hydrocarbon oxidation strategy for the synthesis of chiral polyols is validated by the enantioselective, de novo synthesis of differentially protected L‐galactose (see scheme, TBS=tert‐butyldimethylsilyl, Bn=benzyl). Key to this strategy is the selective CH oxidation method for transforming protected chiral allylic alcohols into (E)‐2‐butene‐1,4‐diol derivatives.

For Abstract see ChemInform Abstract in Full Text.

Direct oxidation of CÀH bonds has the potential to emerge as a powerful approach for introducing oxygen and nitrogen functionality in the synthesis of complex molecules.[1] Functional-group manipulations (FGMs) that are required for carrying oxygenated functionalities throughout a synthetic route may be avoided by installing them directly into the hydrocarbon framework.[2] For a hydrocarbon oxidation strategy to reach its full potential, CÀH-oxidation reactions with high levels of chemo-, regio-and stereoselectivity must be identified and developed. We recently described a DMSOpromoted, Pd(OAc) 2 -catalyzed allylic oxidation reaction that furnishes E allylic acetates from a-olefins with high regio-and stereoselectivity, and with outstanding tolerance of functional groups.[3] Herein, we describe advances in this methodology for the oxidation of CÀH bonds which enabled the development of a new hydrocarbon oxidation strategy for the rapid assembly of polyol frameworks. This strategy has been validated in an enantioselective, de novo synthesis of differentially protected l-galactose from a commercial, achiral starting material in which all new oxygen functionality has been installed through oxidation reactions of CÀH and C=C bonds.A short hydrocarbon oxidation strategy for the synthesis of chiral polyols is presented in Scheme 1. Key to the efficiency of this strategy is the rapid access to chiral (E)-2-butene-1,4-diols such as 2, which may be directly elaborated to polyol structures through asymmetric dihydroxylation (AD). Compounds like 2 are particularly attractive building

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