About the Seminar:
The difluoromethyl functional group (–CF2H) is important in various pharmaceuticals and agrochemicals. This is due to its many advantages, such as behaving as a bioisostere of alcohols, amines, and thiols and lipophilic hydrogen donors through hydrogen bonding. The most common method to add difluoromethyl groups onto an arene is by transition metal catalysis. However, the limitation of this approach is the transmetalation is sluggish in the absence of bases, but the presence of basic additives destabilizes the difluoromethyl nucleophile. Thus, a new strategy to form difluoromethyl arenes and stable nucleophilic difluoromethyl intermediates is highly sought-after. This proposal will develop a novel metal-free difluoromethylation method of arenes via 1,2-boronate migration. Aim 1 will focus on the synthesis of difluoromethylation reagents that will serve two roles first as a nucleophile to add to the aryl boronic ester and then as an electrophile for the 1,2-migration. Aim 2 will examine the 1,2-migration of various substituted aryl boronic esters and Aim 3 will apply this application to late-stage functionalization to install –CF2H. These studies will allow access to valuable difluoromethyl products in drug discovery and agrochemical research.
