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Abstract
The functionalization of unreactive C–H bonds continues to be of great interest, and has led to the development of numerous methodologies. Through the development and utilization of directing groups, major challenges in obtaining high levels of chemo- and regioselectivity have been addressed. This strategy has allowed for the directing group to be temporarily installed and removed following the functionalization of specific C–H bonds. Despite this advancement, a major limitation of this strategy still lies within the number of steps required to complete the transformation. The installation, functionalization, and removal of the directing group often requires multiple steps and purifications, while also using stoichiometric amounts of the directing group. Building on our pyridyl and quinolinyl acetal-directed functionalizations, we aimed to address these issues by developing a scaffold capable of transient C–H functionalization. The use of this scaffold has allowed for installation, functionalization, and removal of the directing group in one reaction using catalytic directing group, compared to the standard three step sequence. During the course of our investigations, we developed a quinolinyl aminal-containing scaffold capable of transiently olefinating (sp2) C–H bonds on benzyl alcohols. Acid-mediated exchange of free alcohol substrates was observed in situ followed by directed C–H olefination, and subsequent cleavage of the directing group to give the ortho-olefinated free alcohol. Additional analysis to assess the full scope and limitations of this transformation were explored.
Furthermore, our investigations into the development of other aminal-containing scaffolds led to the discovery of a non-directed C–H olefination process. While these second generation aminals exhibited exchange capabilities, the preferred reactivity of these scaffolds resulted in a non-directed C–H olefination process.