Decarboxylative Bromooxidation of Indoles by a Vanadium Haloperoxidase
Clare E. Wells, Lauren P.T. Ramos, Lauren J. Harstad, Logan Hessefort, Hyung Ji Lee, Manik Sharma, Kyle F. Biegasiewicz
Abstract
Halooxindoles are versatile building blocks for the construction of complex oxindole-containing targets of biological importance. Despite their synthetic value, catalytic methods to make 3-halooxindoles from readily available starting materials have remained undisclosed. We recently discovered that the chloroperoxidase from Curvularia inaequalis ( Ci VCPO) is a viable catalyst for the decarboxylative bromooxidation of 3-carboxyindoles to furnish 3-bromooxindoles with excellent regio- and chemoselectivity. In addition to the development of the synthetic method, this study provides evidence of a bromide recycling mechanism for the indole oxidation event. A discussion of the reaction development, substrate scope, mechanistic insights, and reaction applicability will be discussed herein.