The disappointing stereoselectivity in the formation of 4 is perhaps unsurprising; we have previously identified that AT-CuAAC auxiliary approaches to MPC rotaxanes only proceed efficiently when a sterically hindered -chiral azide half-axle is used. 19b,f This is hard to realize practically in the case of the MGI-2 stereogenic unit as it would nominally require iterative CuAAC couplings of a 1,1-bis-azide synthon. Thus, we returned to our comparison of the MPC and MGI-2 stereogenic units and recognized that our chiral interlocking auxiliary strategy, 19f which reliably loads macrocycle 1 onto the axle of almost any rotaxane in a specific orientation that is determined by the absolute stereochemistry of the amino acid-derived azide used, corresponds to the desired notional oriented threading process (Figure ).