Oxidative Cyclizations in a Nonpolar Solvent Using Molecular Oxygen and Studies on the Stereochemistry of Oxypalladation

Abstract

Oxidative cyclizations of a variety of heteroatom nucleophiles onto unactivated olefins are catalyzed by palladium(II) and pyridine in the presence of molecular oxygen as the sole stoichiometric oxidant in a nonpolar solvent (toluene). Reactivity studies of a number of N-ligated palladium complexes show that chelating ligands slow the reaction. Nearly identical conditions are applicable to five different types of nucleophiles: phenols, primary alcohols, carboxylic acids, a vinylogous acid, and amides. Electron-rich phenols are excellent substrates, and multiple olefin substitution patterns are tolerated. Primary alcohols undergo oxidative cyclization without significant oxidation to the aldehyde, a fact that illustrates the range of reactivity available from various Pd(II) salts under differing conditions. Alcohols can form both fused and spirocyclic ring systems, depending on the position of the olefin relative to the tethered alcohol; the same is true of the acid derivatives. The racemic conditions served as a platform for the development of an enantioselective reaction. Experiments with stereospecifically deuterated primary alcohol substrates rule out a "Wacker-type" mechanism involving anti oxypalladation and suggest that the reaction proceeds by syn oxypalladation for both mono-and bidentate ligands. In contrast, cyclizations of deuterium-labeled carboxylic acid substrates undergo anti oxypalladation.

Transition metals in organic synthesis: Highlights for the year 2005

“…The stereochemistry of oxidative intramolecular alkoxypalladations was studied [843]. Oxidative intramolecular alkoxy-palladation (formally alkoxy-palladation-␤-elimination) of a pendant alkene was used to form functionalized furans and benzofurans [440,844], dihydropyranones and furanones [845], (−)-15-oxopuupehenol [846], garsubellin A (Eq.…”

H-Transfer steps of the Wacker process: A DFT study

“…Hence, the energy barriers of the steps occurring after the RDS should be lower than these calculated E a s. The suggestion of H-transfers sequence (Eqs. (6)- (8)) is based on the absence of any deuterium isotope incorporation when the This step has been studied in several cases. The experimental isotopic effects [14,[17][18][19][20] clearly indicate that the bHE step could not be the RDS of the reaction.…”

Palladium‐Catalyzed Formation of Cyclic Ethers – Regio‐, Stereo‐ and Enantioselectivity of the Reaction

“…[2,3,5] A large variety of oxygen-containing heterocycles have been obtained with this methodology, [26][27][28][29][30][31][32][33][34] even in an asymmetric fashion. [35][36][37] In our continuing interest in Pd-catalyzed access to substituted THFs and tetrahydropyrans, we were interested in the synthesis of such functionalized oxygen heterocycles. Recently it was reported that ω-hydroxy-α,β-unsaturated alcohols underwent an intramolecular Pd II -catalyzed cycli-zation to give vinyltetrahydropyrans.…”