As a direct route to the trans-substituted isomers we developed a one-pot arylation-epimerization. Simple addition of DBU to the reaction mixture after the arylation step promoted epimerization of cis-arylated products to corresponding transdiastereomers 17 and 18 at 100 ° C (Scheme 4). A 24 h heating time promoted the majority of the cis-isomer to epimerize, with a 70% conversion of the cis p-methoxyphenyl-substituted piperidine and a 90% conversion of the cis p-bromophenyl substituted substrate, to afford trans products 17 and 18 in 54% and 53% isolated yields, respectively. Finally, the directing group was removed to unveil polar functionalities and access fragments and building blocks of interest for drug discovery programs (Scheme 5). 30 Scheme 5. Divergent aminoquinoline removal. a a AlogP and Polar Surface Area (PSA) calculated using Llama. Molecular weights corresponding to the free amines.