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. 2005 Dec 21;127(50):17778-88.
doi: 10.1021/ja055534k.

Oxidative cyclizations in a nonpolar solvent using molecular oxygen and studies on the stereochemistry of oxypalladation

Raissa M Trend  1 , Yeeman K Ramtohul, Brian M Stoltz
Affiliations

Oxidative cyclizations in a nonpolar solvent using molecular oxygen and studies on the stereochemistry of oxypalladation

Raissa M Trend et al. J Am Chem Soc. .

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.

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Figures

Figure 1
Figure 1
Prototypical Pd(II)-catalyzed dehyrogenation reactions.
Figure 2
Figure 2
An oxidase-type kinetic resolution of secondary alcohols.
Scheme 1
Scheme 1
Cyclization of deuterium-labeled primary alcohol substrates with pyridine as ligand.
Scheme 2
Scheme 2
Three oxypalladation pathways.
Scheme 3
Scheme 3
Attempted cyclization of a terminal olefin-appended phenol.
Scheme 4
Scheme 4
Cyclization of deuterium-labeled primary alcohol substrates with dipyridyl as ligand.
Scheme 5
Scheme 5
Comparison of reaction pathways with a monodentate and bidentate ligand.
Scheme 6
Scheme 6
Cyclization of deuterium-labeled carboxylic acid substrates with pyridine as ligand.
See this image and copyright information in PMC

References

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