Wacker Oxidation, The

Terminal alkene substrates can be converted to methyl ketone products via a palladium-catalyzed process known as the Wacker oxidation. This process has found widespread application in targeted synthesis, since alkene substrates are easily accessed and unreactive under diverse reaction conditions substrates and the resultant carbonyl products are common precursors for diverse synthetic manipulations. This chapter covers the application of the Wacker oxidation and variations of the Wacker oxidation to various types of alkene substrates. The literature covered spans the inception of the reaction in 1959 through November 2012. A discussion of the current mechanistic understanding is presented, emphasizing considerations that are relevant to synthetic application, including how the nature of the alkene substrate and nucleophiles other than water are proposed to influence the mechanistic pathways and ultimately the product distribution. The “Scope and Limitations” section is separated into discussions relating to functional group tolerance, the influence of heteroatoms proximal to the alkene substrate, and Wacker-type oxidations that do not result in carbonyl products, such as cyclization reactions and aza-Wacker reactions. Select applications of the Wacker oxidation in total synthesis are presented, as well as a comparison to other methods and examples of experimental conditions. Keywords: Wacker oxidation(s); palladium-catalyzed; nucleopalladation; oxypalladation; alkene(s); olefin(s); ketone(s); Markovnikov addition; anti-Markovnikov addition; ligand-modulation; molecular oxygen; tert-butylhydroperoxide; Benzoquinone; allylic alcohol(s); homoallylic alchol(s); allylic amine(s); homoallylic amine(s); Wacker cyclization; acetal(s); aza-Wacker