Acetanilides, oxidative cyclization

Hartwig has reported an intramolecular/intermolecular process affording the 3-aryloxindoles 105 (Scheme 32).115 The intermolecular arylation of acetanilide derivative 104 is slower than the intramolecular arylation to form the oxindole. Thus, the overall transformation starts with cyclization followed by intermolecular arylation of indole. In order to slow down the intermolecular process and speed up the intramolecular reaction, chloroarene and bromine-substituted acetanilide precursors are used according to their respective reactivity with palladium(O) in the oxidative addition process. 

In 2015, Liu and coworkers reported the formal synthesis of tipifarnib, a farne-syltransferase inhibitor, by using a palladium-catalyzed C-H alkenylation as a key step (Scheme 16.35) [71]. Aniline derivative 160 reacted with AC2O to form an acetanilide intermediate, followed by ort/zo-palladation under the influence of a palladium catalyst to produce compound 162. Oxidative Heck reaction with 161 and cyclization/deacetylation then occurred to afford quinolinone 163 in 95% yield in one pot. This quinolinone was then converted to tipifarnib by the reported procedure [72]. 

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