Optimization of the asymmetric hydrosilylation/hydroamination reaction. Building on our previous results with copper-functionalized BTA helices and inspired by the possibility to engage Cu-H catalysts in sequential transformations, we selected 3-vinylacetophenone (VPnone) as the substrate to implement our concept. Initial tests have been conducted with DTBM-SEGPHOS (Table ), a covalent diphosphine ligand, since its combination with [Cu(OAc)2] proved to be highly efficient in a wide range of reactions involving Cu-H active species, furthermore cascade hydrosilylation (HS) /hydroamination (HA) reaction of non-conjugated vinyl and ketone functions have not been reported yet. VPnone was first mixed with a 1:1 mixture of (S)-DTBM-SEGPHOS and (R)-DTBM-SEGPHOS, in presence of [Cu(OAc)2], with dimethoxymethylsilane (DMMS) and N,Ndibenzyl-O-pivaloylhydroxylamine (Amine-tBu) as the reducing and aminating agents, respectively. The reaction conducted in a sequential manner, i.e. by engaging Amine-tBu after completion of the hydrosilylation of the ketone function, yields the expected amino alcohol, 1-[3-(1-dibenzylaminoethyl)]-acetophenol (APnol), as a 1.0/1.3/1.0/1.4 mixture of the four stereoisomers according to its HPLC trace (Figure ). The diastereomeric ratio (dr), close to 1:1, is an indication that the selectivity of the reaction is mostly controlled by the catalyst, not the substrate. Performing the reaction with (R)-DTBM-SEGPHOS under conditions resembling those reported by Buchwald and co-workers for the asymmetric HS/HA of enals, yields APnol in 56% yield, 99% enantiomeric excess (ee) and a diastereomeric ratio of 9:1 (Table and Figure ). As expected, (S)-DTBM-SEGPHOS provides the corresponding enantiomer with similar yield and selectivity. In these reactions, 3-ethylacetophenol (EPnol) also forms in small amount, probably as a result of the protonation of the alkyl copper catalytic species by residual water (see Figure and the SI). Table Asymmetric hydrosilylation/hydroamination reaction of VPnone with DTBM-SEGPHOS as ligand. See the SI and Figure for more details. The indicated yield is an isolated yield. The enantiomeric excess and diastereomeric ratio are obtained from the chiral HPLC analyses of purified APnol. Ee1 (positive for the (R)enantiomer of the alcohol) and ee2 (positive for (S)-enantiomer of the amine) are extracted from the HPLC traces as indicated in Figure and this convention was followed throughout this paper. Error bars: main stereoisomer ±1%, ±1% ee, ±0.2 dr, ±1% ee1, ±1% ee2 when (R,R)-or (S,R)-APnol is the main stereoisomer, main stereoisomer ±2%, ±1% ee, ±0.4 dr, ±3% ee1, ±1% ee2 when (S,S)-or (R,S)-APnol is the main stereoisomer (see the general methods in the SI).