Metal-catalyzed C-H functionalization has enormous potential to aid diverse functionalization along C(sp )-H bonds. Regiocontrol remains a challenge in saturated heterocycles, where the C(2) position is considerably more activated than C-H bonds away from the heteroatom. Palladium-catalyzed methods have been developed to allow regio-and stereocontrolled functionalization of the more challenging remote positions by exploiting directing groups (Figure ). In 2014 we reported the selective C(3) cis-arylation of proline derivatives using an aminoquinoline directing group. cis-Functionalization of piperidines and O-heterocycles with C(2) auxiliaries have subsequently been demonstrated, as well as other ring sizes. Moving the directing group to the C3-position presents further selectivity requirements. We recently reported the selective C(4) arylation of piperidines and pyrrolidines with a C(3) aminoquinoline amide. Maes reported the use of a C(3) picolinamide/directing group to form 3,5-syn-disubstituted piperidines, and Sanford developed C(4) piperidine functionalization using an N(1)-linked directing group. Notably, many of these reports obtained high levels of diastereoselectivity, often due to local steric requirements or stereospecific mechanistic features, though different, and often forcing reaction conditions were required. The C-H functionalization of 6-membered heterocycles with C(4) directing groups remains little studied with only a few isolated examples to date. Achieving high conversion with these substrates presents an additional challenge due to the potential for diarylation. Furthermore, these examples have commonly seen low diastereoselectivity. Yu reported early single examples of arylation, and alkynylation 25 on tetrahydropyrans. In 2016 Yu developed C(3) arylation of N-heterocycles with a C(4) directing group as part of a broader study using Pd-catalysis with an NHC ligand, with low diastereoselectivity (Figure ). More recently, Yu reported an O-linked C4 directing group with a single example on a tetrahydropyran (2:1 cis:trans). Here we report the stereoselective synthesis of cis-3,4-disubstituted piperidines and tetrahydropyrans, by C(3) arylation in the presence of a C(4) aminoquinoline amide directing group (Figure ). Notably, using moderate temperatures (45-50 °C) achieved high selectivity for mono-cis functionalization on the unbiased C(4)-substituted 6-membered ring. To date, this constitutes the first heterocycle C(sp 3 )-H functionalization protocol at unactivated positions to not require high temperatures. This method allows generation of attractive fragments for screening as single diastereoisomers.