Late stage functionalization has emerged as an attractive strategy for the diversification of lead compounds in drug development, not only because of its step reducing nature but also as a means of accessing synthetically challenging compounds. Many of these rely on transition metal catalyzed C-H activation enabled by coordination to a directing group. Ideally such late stage functionalization protocols take advantage of the directing effect of functional groups that are already present in the biologically active compound in order to provide predictable selectivity for specific C-H bonds. At the same time, a high level of functional group tolerance is key to allow for the functionalization of unprotected complex molecules.<br/>Herein we will present our efforts on the installation of small substituents or additional points of diversity (diversity oriented LSF). Utilizing cobalt and iridium precatalysts we have developed different C-H functionalization protocols where the chemistry is facilitated by a broad scope of directing groups commonly found in organic molecules taking advantage of coupling partners that are compatible with most functional groups. To highlight the applicability of the transformations, a diverse array of biologically active molecules have been functionalized in one simple step, thus avoiding the need for prefunctionalization or post-reaction deprotection.

Directed C–H activation using cobalt or iridium: Applications in medicinal chemistry

2019 Fall National Meeting

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