Previously we have found that the diastereoselectivity of the AT-CuAAC reaction is highly dependent on the steric demand of the alkyne and azide components to the point where a chiral auxiliary that is highly stereoselective (96% ee) with one coupling partner, is entirely unselective with another substrate. Although this issue can be overcome using our recently introduced chiral interlocking auxiliary approach, macrocycles 1 would represent a complementary approach if they were suitable for the synthesis of a range of targets. Thus, we briefly investigated how substrate structure affected the diastereoselectivity of the reactions mediated by macrocycles (S)-1b and (S)-1e (Figure ).