Sequential HS/HA transformation with a stereochemically switchable BTA helical catalyst. The sequential transformation was first conducted without adding the enantiopure BTA (the chemical stimulus that triggers the stereochemical switch, vide supra) after completion of the HS step, i.e. the BTA helical catalyst has the same handedness for both HS and HA reactions. Except for the sequential addition of the reactants, the reaction was conducted similarly to the catalytic screening mentioned above, i.e. without exclusion of air. APnol also forms under these conditions but in a significantly lower yield (29±10 % NMR yield, Table , entry 1) compared to the aforementioned concomitant process (76±5% NMR yield, Table , entry 2). In addition to APnol, 22% and 17% of EPnol and VPnol are detected, respectively (Figure ). The lower yield of the sequential process performed under air is thus related to the formation of by-products that likely originate from VPnol. However, the selectivity in APnol is similar to the concomitant reaction with only a small drop in the ee for the HS and HA steps which seems to be inherent to the different catalytic species present in the sequential process (see above for the discussion on the ee of the HS only reaction). Importantly, comparing the results of the entries 1 and 2 in Table indicates that the optimal selectivity is reached whatever chiral induction occurs through a single enantiomer of the BTA monomer (similarly to the initial conditions before inversion of the catalyst handedness) or by means of a scalemic mixture of the BTA monomers (similarly to the conditions after inversion of the catalyst handedness). We next envisioned to perform each step of the sequential process with the BTA helical catalyst having opposite handednesses as probed by CD spectroscopy in Figure . Even though the proportion of by-products can be minimized by conducting the reaction under O2-free and strictly anhydrous conditions (vide infra), the following experiments were performed under air since the time required for the HS step and the stereochemical switch have been established under these conditions (Figure ). We were pleased to see that the (R,R) and (S,S) stereoisomers of APnol are now the major stereoisomers when the handedness of the catalyst is switched from right to left and left to right before the HA step, respectively (Table , entries 3 and 4). Enantiomeric excesses for each step have opposite signs as expected for reactions conducted with a catalyst displaying opposite intrinsic enantioselectivities. However, the values of ee2 in entries 3 and 4 indicate that the selectivity of the HA step is not optimal, thus lowering the overall selectivity of the sequential reaction. This is likely due to the fact that the stereochemical switch was not complete before the addition of Table Transformation of VPnone into APnol through sequential HS and HA steps involving the BTA helical catalyst having the same (entries 1-2) or opposite handednesses (entries 3-6) for both steps. For entries 3-6, the handedness of the BTA helical catalyst is switched after 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. The reactions are performed without exclusion of air. See Figures and for the 1 H NMR spectra of the crude samples of entry 1 and entries 5-6, respectively. An internal standard is used to measure the yield in APnol on the crude samples. The enantiomeric excess and diastereomeric ratio are obtained from the chiral HPLC analyses of the crude samples. Error bars for ee and dr: see footnote of Table .