Amine-tBu and thus a small fraction of the silyl ether of VPnol (estimated to ca. 20%) was converted by catalytic helices (or helical fragments) of the unwanted, non-switched handedness. We attribute this discrepancy between the time of stereochemical switch probed by CD spectroscopy (Figure ) and that deduced from these catalytic experiments by a slower dynamicity of the supramolecular helices embedding the catalytic active species/resting states versus the pre-catalytic species. Whilst related supramolecular BTA terpolymers with copper acetate complexes anchored at their periphery have been found to be well-soluble single helices, it can be surmised that the generation of hydride species, that tend to bridge several copper atoms, may generate aggregated supramolecular helices through copper crosslinks that are expected to be less soluble and less dynamic under our experimental conditions. This might also explain why the rate of the stereochemical switch in the present case (on the timescale of minutes) is slower than in our previous study dealing with HS only and for which the switch occurred on the timescale of seconds. This negative effect was ultimately circumvented by lowering the amount of a-BTA to 5 mol% (Table , entries 5 and 6), which probably leads to slightly shorter and more dynamic terpolymers as a consequence of the decrease of the total BTA monomer concentration. The (R,R) and (S,S) stereoisomers of APnol are now obtained with a selectivity that matches the one obtained for the sequential reaction performed without stereochemical switch and is not too far from that of the concomitant process: ca. 70% and 78% of the main stereoisomer of APnol for the sequential and concomitant processes, respectively (compared data in Tables and). Having established that a full inversion of the catalyst handedness can be achieved under air in the conditions similar to those probed in Figure , we next turn to O2-free and anhydrous conditions to improve the efficiency of the sequential reaction. Initial experiments show that the rate of the HS step is Sequential HS and HA reactions involving the BTA helical catalyst displaying opposite handednesses for both reactions. Reactions have been conducted on 1 mmol scale of VPnone under strict exclusion of air and water (see Figure for 1 H NMR spectra of the crude samples). The handedness of the BTA helical catalyst is switched after presumed completion of the HS step as schematized by adding 15 mol% of (R)-BTA or (S)-BTA to solutions that initially contain 5 mol% of (S)-BTA or (R)-BTA. Both NMR (via an internal standard on a crude sample) and isolated yields in APnol are provided. The enantiomeric excess and diastereomeric ratio are obtained from the chiral HPLC analyses of the purified samples. Error bars for ee and dr: see footnote of Table . dramatically decreased under these conditions, an observation which agrees well with the well-documented but counterintuitive ability of phosphine-based copper catalysts to exhibit enhanced activity when HS is performed under air. The reaction time of the HS step was thus increased to one hour and the overall reaction timescale was extended (Table ). APnol can now be isolated in ca. 40% yield, close to the isolated yield obtained in concomitant processes, confirming that by-products are significantly minimized under these conditions (Figure ). The (R,R) and (S,S) stereoisomers of APnol are obtained as the main stereoisomers as expected for each step being promoted by a helical catalyst with opposite handednesses, but with a lower selectivity (ca. 80% ee, dr= 1.3:1) compared to the same reaction performed under air. Examining the enantiomeric excess of each step reveals that the origin of the lower selectivity comes from the HS step, which is far from being optimal, indicating that the HS of VPnone is not completed before the stereochemical switch. More precisely, the enantioselectivity of the HS step (ee1, Table ) is of ca. 20% consistent with ca. 35% of VPnone being converted after the switch of the catalyst handedness. In contrast, the selectivity of the HA step is of ca. 70% ee, with opposite sign compared to ee1, which is expected for HA reaction performed with the catalyst of fully inverted handedness, inferring that full stereochemical switch occurs under these conditions. Attempts to improve further the selectivity of the sequential reaction performed under nitrogen and anhydrous conditions towards the (R,R) and (S,S) stereoisomers of APnol were not successful since a delicate balance between catalyst activity (for HS step) and catalyst dynamicity (for the stereochemical switch) was not reached (Table ). In overall, performing the reaction under nitrogen significantly increases the yield of the sequential reaction but drastically changes the kinetics of the HS step that makes difficult to achieve optimal selectivity under these conditions. The four stereoisomers of APnol can anyway be obtained with similar selectivities either from a concomitant process in which both steps are performed with a left-handed or right-handed helical catalyst or sequential reactions (under air) in which the handedness of the BTA helical is fully switched in between the HS and HA steps (Figure ). Dual catalysis and cascade catalysis are the most efficient strategies to achieve asymmetric stereodivergent with molecular catalysts but require several catalysts and/or multi-pot procedures because of the non-dynamic nature of the catalysts engaged in these reactions.