Enantio- and Regioselective CH-Functionalization of Cycloalkanes
Final Report Abstract
In the period funded by the DFG, I established a synthetic access to the decalin carboxamide 8 in 25% total yield and six steps starting from known enone 2. Simultaneously, I was involved in developing a new class of ligands for Pd-catalyzed enantioselective CH-functionalization. These acetyl protected aminoetylquinoline (APAQ) ligands enable CH-functionalization of methylene sp3-CH-bonds in terminal alkylamides, as published in Science1. Unfortunately, amide 8 was completely unreactive in CH-activation with all ligands tested, presumably due to steric bulk induced by a quartenary carbon atom in its αposition. Switching from the rigid bicyclic alkane to linear alkanes with internal directing groups such as 12, 15 and 18 only gave unsatisfactory results, also presumably because of steric bulk induced by a tertiary carbon atom in the α-position. Gratifyingly, cyclohexane carboxamide 19 undergoes arylation smoothly. The newly developed APAQ-ligands enable CH-activation of cyclohexane 19 with good enantioselectivity and unprecedented control of cis/trans-diastereoselectivity.
