Overcoming challenges in selective Wacker-type oxidation reactions

Abstract

The Wacker oxidn. has proven to be a powerful reaction for the oxidn. of simple olefins to Me ketones. However, important limitations restrict its application in the lab. setting. Typically, oxidns. of simple terminal olefins occur with Markovnikov selectivity, while achieving high aldehyde selectivity has historically been more challenging. Addnl., internal olefins are generally unreactive under Wacker oxidn. conditions. Our group has recently devoted research efforts toward addressing these limitations. Specifically, during studies of a dicationic palladium catalyst capable of oxidizing internal olefins, it was obsd. that electron-withdrawing trifluoromethyl groups are capable of significantly enhancing selectivity for distal, rather than proximal, oxidn.; even modest aldehyde selectivity was achieved in the case of an electron deficient terminal olefin. Gaining inspiration from this system, we have developed a method for the anti-Markovnikov oxidn. of terminal olefins bearing electron deficient fluoride groups, providing direct access to beta-fluorinated aldehyde products. Preliminary mechanistic studies reveal the importance of a key inductive effect in influencing aldehyde selectivity. Furthermore, research efforts toward understanding and controlling regioselectivity with regard to substrate substructure, as well as progress toward enantioselective processes, will be described.