Unconventional Site Selectivity in Cross-Couplings of Dihaloheteroarenes

Heteroarenes are ubiquitous motifs in high-value small molecules including pharmaceutical drugs and agrichemicals. Elaboration of halogenated heteroaromatic cores can be achieved through cross-coupling reactions, which are among the most widely used methods in organic synthesis. However, when two or more halides are present on the substrate, controlling site selectivity becomes critical. In fact, cross-couplings often follow a predictable selectivity pattern. For many dihalogenated heteroarenes, methods do not exist to reliably invert the conventional pattern to achieve cross-coupling at the \"less reactive\" C—X bond. Herein we describe new catalyst-controlled strategies to accomplish this goal, together with mechanistic studies to explain the origin of the selectivity inversion.


Sharon Neufeldt (Montana State University)