Discovery of a Practical Direct O₂-Coupled Wacker Oxidation with Pd[(−)-sparteine]Cl₂

Abstract

The discovery of a direct O2-coupled Wacker oxidation with use of balloon pressure of O2 and low catalyst loading is described. Use of (-)-sparteine as a ligand on Pd prevents olefin isomerization and leads to selective formation of methyl ketones from terminal olefins in good yields. Oxidation of enantiomerically enriched substrates is reported with no observed racemization.

Total synthesis of proposed cephalosporolides H and I

“…In contrast, the characteristic of our S-product 1b matched well with the data of natural product, 5 except for C-12 on alkyl chain shown chemical shift at 33.8 ppm for natural product and 35.5 ppm for synthetic sample in 13 To prepare both cephalosporolides H and I efficiently, a more reliable and stereo-controllable strategy is required. We thus focused on the investigation of Wacker oxidation 22 for the common core structure 3. Replacement of X group with chloride, Ms, and Ts in 3, respectively, followed by Wacker oxidation under standard reaction conditions afforded some encouraging results.…”

Palladium‐Catalyzed Oxidation of Phenyl‐Substituted Alkenes using Molecular Oxygen as the Sole Oxidant

“…[15] The enhancing effect of water has also been observed in the Pd[(À)-sparteine]Cl 2 /DMA system for the oxidation of other terminal alkenes. [14] However, it should be mentioned that increasing the water concentration must be equilibrated with the miscibility of the substrates.…”

“…To overcome these problems, much effort has been devoted to the development of alternative halide-free co-catalysts, such as CuA C H T U N G T R E N N U N G (OAc) 2 , heteropoly acids, nitrates, and benzoquinone; [2][3][4][5][6][7][8] as well as, more recently, palladium catalysts modulated by special ligands. [8][9][10][11][12][13][14] In the latter systems, oxidatively robust (usually, nitrogen-containing) ligands are used to stabilize reduced palladium and promote its regeneration directly by molecular oxygen avoiding the use of corrosive additives. A few examples of the ligand-modulated palladium-catalyzed oxidations of terminal alkenes into methyl ketones using molecular oxygen as the sole oxidant have been published.…”

“…A few examples of the ligand-modulated palladium-catalyzed oxidations of terminal alkenes into methyl ketones using molecular oxygen as the sole oxidant have been published. [9][10][11]14] Recently, Kaneda and co-workers have discovered that dimethylacetamide (DMA) as a solvent serves to stabilize a palladium catalyst preventing its precipitation into inactive metal and to promote a direct dioxygen-coupled Wacker oxidation of a number of terminal alkenes. [15] The system allows for an efficient catalytic turnover without the need for additional cocatalysts or special ligands under relatively mild conditions (80 8C, 6 atm of oxygen).…”

“…Sigman and co-workers have achieved a further improvement in the practicality of this reaction showing that the use of (À)-sparteine as a ligand on palladium allows one to perform the reaction in a DMA/H 2 O solvent system under balloon pressure of oxygen. [14] Inspired by these disclosures, we have decided to extend their applications to phenyl-substituted alkenes, i.e., styrene and 2-vinylnaphthalene. These alkenes are usually problematic substrates for oxidation due to a tendency toward oxidative cleavage to the corresponding aldehydes and polymerization.…”