The Pd(OAc)2/O2/DMSO catalyst system displays impressive versatility in the aerobic oxidation of organic substrates, ranging from alcohols to olefins. This report details mechanistic insights into these reactions. Dimethyl sulfoxide (DMSO) plays no redox role in the chemistry, and kinetic experiments identify the turnover-limiting step as DMSO-promoted oxidation of palladium(0) by molecular oxygen. The "chemical oxidase" pathway characterized for this catalyst system holds great promise for the design of new aerobic oxidation reactions.

Facile and efficient: a palladium‐catalyzed intramolecular oxidative amination reaction [Eq. (1)] that uses molecular oxygen as a stoichiometric oxidant. These reactions require no cocatalyst for efficient reoxidation of the palladium, they operate in solvents ranging from heptane to dimethylsulfoxide, and achieve up to 250 turnovers (TO) and rates of 70 TO h−1.

No abstract

The prominence of five-membered nitrogen-containing heterocycles in natural products and biologically active molecules [1] has prompted considerable efforts toward their synthesis. Intramolecular hydroamination [2, 3] and oxidative amination [4,5] of olefins represent powerful synthetic strategies for heterocycle formation (Scheme 1). [6] The latter isOxH 2 hydroamination oxidative amination Scheme 1. Strategies for the heterocyclization of olefinic amines or amides.particularly attractive in the context of target- [7] and diversityoriented [8] synthesis, because the product retains the olefin functionality. Nevertheless, oxidative methods exhibit added complexity associated with redox catalysis, specifically the need for a stoichiometric oxidant, which is typically an organic or a transition metal reagent such as benzoquinone or CuCl 2 . [9] Furthermore, catalytic rates (< 1 h À1 ) and turnover numbers ( 10 ± 20) are significantly lower than those of hydroamination reactions, for which turnover numbers of ! 300 and frequencies of 50 h À1 are not uncommon. [2] We describe herein the application of a very simple and efficient catalyst system, [Pd(OAc) 2 ]/pyridine (1:2), for the intramolecular oxidative amination of olefins to produce pyrrolidine and pyrroline heterocycles in high yields. These reactions utilize molecular oxygen as the stoichiometric oxidant, require no co-catalyst to facilitate the dioxygen-coupled catalytic turnover, and achieve unprecedented catalytic activity for such reactions.Our recent mechanistic studies of the [Pd(OAc) 2 ]/O 2 / DMSO catalytic oxidation system [9] revealed that oxidation of reduced palladium by molecular oxygen is the turnoverlimiting step of the catalytic cycle. [10] By analogy to recent aerobic oxidation reactions of alcohols, [11±13] we reasoned that pyridine or other imine donor ligands might promote palladium oxidation and thereby increase catalytic efficiency in oxidative amination reactions. Indeed, the oxidative cyclization of (E)-4-hexenyltosylamide (1) worked remarkably well with a catalyst composed of [Pd(OAc) 2 ] (5 mol%) and pyridine (10 mol %) under one atmosphere of molecular oxygen [Eq. (1)]. The pyrrolidine product 2 was obtained in high yield (87 %) within two hours. NHTs Ts N 5 mol% [Pd(OAc) 2 ] toluene, 80 °C (1) 10 mol% pyridine 1 2 + H 2 O + O 2 / 1 2Unlike previous aerobic oxidative amination reactions, this catalyst system operates successfully in a diverse array of solvents (! 80 % yield), ranging from nonpolar (toluene, xylenes, heptane, and diphenyl ether) to polar (dimethoxyethane, acetonitrile, dimethylsulfoxide, and dimethylformamide). The precise role of pyridine in more polar, potentially coordinating solvents remains to be determined.Nonpolar solvents proved to be distinctly superior at lower catalyst loading. The use of [Pd(OAc) 2 ] (0.2 mol %)/pyridine (0.4 mol %) in p-xylene resulted in turnover rates of 70 h À1 during the first two hours of the reaction and overall turnover numbers up to 250 ± 300. [14] These catalyst activities far...

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.