Research On Palladium-Catalyzed Oxidation Of Alkenes And Alkynes With Molecular Oxygen

Alkenes and alkynes are important precursors in organic synthesis. Transition metal catalyzed oxidation of alkenes or alkynes to fine chemicals continues a very important field of organometallic chemistry. The activation of alkenes or alkynes can be induced by their coordination to the metal, which makes the bonds susceptible to addition reactions. Among the transition metals, palladium plays an important role in organometallic chemistry, which can exists in three easily interconvertible oxidation states: Pd（0）, Pd（Ⅱ）, and Pd（Ⅳ）. Further more, the reaction conditions can be tuned by varying the ligand, base, solvent, temperature, and additives to optimize the desired process. Currently, Cu²⁺ salt, BQ, PhI（OAc）₂, peroxide and oxone are widely used in Pd（Ⅱ）/oxidant agent catalytic system. However, these oxidants are expensive and polluting the environment. Molecular oxygen is an abundant and environment benign oxidant. Generally speaking, Pd（Ⅱ）/O₂ catalytic system have higher selectively and under milder reaction conditions as compare to KMnO₄, OsO₄, RuO₂ and O₃. Therefore, the utilization of molecular oxygen as oxidant in palladium catalyzed oxidation of alkenes and alkynes are highly desirable.In this context, we have studied the palladium-catalyzed transformation of alkenes and alkynes with molecular oxygen, and several novel oxidation methods were developed. The details are summarized as following:（1） Palladium-catalyzed oxidative cleavage of alkynes. The cleavage reaction of alkynes is one of the most challenging subjects in modern synthetic organic chemistry. Generally, the cleavage of C-C triple bond is achieved by using KMnO₄, alkaline H₂O₂, ozone, OsO₄ and RuO₄. We have developed a new Lewis acid promoted and palladium-catalyzed cleavage reaction with molecular oxygen in which alkyne is split into carboxylic ester in various alcohols.（2） Palladium-catalyzed cyclization of aromatic alkynes to tetrasubstituted furans. Tetrasubstituted furans represent one of the most prominent classes of five-membered heterocycles. Transition metal catalyzed cycloisomerization of unsaturated acyclic precursors to prepare multiply substituted furans has attracted much attention, but these methods require the preparation of rather advanced starting materials, such as allenyl ketones, alkynyl ketones, or epoxides. We developed a novel method for synthesis of tetrasubstituted furans from readily available alkynes via the palladium catalyzed and Zn（OTf）₂ promoted cyclization process. This protocol not only utilized the easy available starting materials but also have good selectivity. （3） Palladium-catalyzed cis-dihydroxylation and oxidative cleavage of olefins. Alkene dihydroxylation and oxidative cleavage reactions are highly versatile synthetic methods for the preparation of valuable intermediates. These reactions classically carried out by high-valent oxometals such as RuO₄ and OsO₄. However, its utility is often limited by safety concerns and high cost. We developed an efficient oxidation of a wide range of olefins to 1,2-diols, aldehydes or ketones catalyzed by palladium with O₂ as sole oxidant. These reactions constitutes an economically attractive and environmentally friendly synthesis of 1,2-diols and carbonyl compounds and may be suitable for large-scale operations.（4） Palladium-catalyzed diacetoxylation of alkenes. Currently, there is considerable interest in the palladium-catalyzed alkene difunctionalization, such as alkene diamination, aminoacetoxylation and dioxygenation. One common ground of these reactions is that PhI（OAc）2 was used as an oxidant to oxidize Pd^Ⅱto Pd^Ⅳ. However, as a stoichiometric oxidant, PhI（OAc）₂ often produces a large amount of by-products （PhI）. We developed the first examples of Pd-catalyzed diacetoxylation of alkenes using oxygen as the sole oxidant to afford diacetates. High levels of diastereoselectivity in diacetoxylation of 1, 2-disubstituted alkenes was obtained （syn:anti > 95:5）.（5） Palladium-catalyzed carbonation-diketonization of terminal aromatic alkenes for the synthesis of 1,2-diketones. 1,2-diketone derivatives are important structural units and synthetic intermediates in biologically active natural products and medicinal chemistry. In connection with our interest in the search for new alkene oxidations, we developed a palladium catalyzed carbonation-diketonization reaction of terminal alkenes with molecular oxygen as the oxidant to synthesize 1,2-diketone derivatives. In this reaction, the C-C bond formation via C-N bond cleavage has been achieved with nitroalkanes as the coupling partners.（6） Palladium-catalyzed cyclization of homoallylic alcohols toγ-lactones. Theγ-lactone structure is a ubiquitous unit in a variety of natural products and active pharmaceuticals. The classical synthesis ofγ-lactones involves the intramolecular esterification of 4-hydroxybutanoic acid or the Baeyer-Villiger oxidation of oxetanes. The oxypalladation of homoallylic alcohols usually give furyl-palladium intermediates, which were converted toγ-butyrrolactones via the optimization of the reaction conditions.