The development of traceless and transient directing group strategies and complementary diastereoselective alkylations of imidazolidinones

Abstract

The functionalization of unreactive bonds has been the focus of numerous new methodologies. Some major challenges lie in obtaining high levels of chemo- and regioselectivity in a minimal number of steps. To address these challenges, we aimed to develop a strategy where a temporarily group is installed to direct functionalization to a specific C–H bond. We focused our investigations toward developing that group for the functionalization of sp2 C–H bonds of benzyl alcohols and ultimately developed a group that directs both alkenylations and arylations. It outcompetes other directing groups and functionalizes C–H bonds that are notably remote from this temporary group. During the course of our investigations, we envisioned this new group’s potential utility as a transient ligand capable of directing C–H functionalizations. This would entail the ligand covalently attaching temporarily to a substrate prior to functionalization. Additional strategies were explored to realize this ultimate goal. Furthermore, our investigation into ligands for C–H functionalization led to the discovery of stereo-divergent outcomes in the alkylation of imidazolidinones. High levels of either cis or trans configured products were obtained by substituting the attached temporary group. If this group is 1-naphthyl, high levels of trans products were observed. This contrasts the selectivity of the bulky isopropyl group and led us to investigate a potential electrostatic interaction as the rationale for diastereoselectivity.