The known dialkyl acetate 8 was selected as the first substrate to launch optimization and feasibility studies (Table ). This simple compound has been prepared previously using strategy A (Figure ) in a five-step process relying on the nucleophilic addition of iPrMgBr to epoxide 9. In principle, the envisaged single electron approach would truncate the route to two steps and increase convergency. The first experiments conducted were comparisons with the closest literature precedents for such a reaction from G.C. Fu and co-workers (Table ). Thus, subjection of a-bromo acetate or benzoate 12 to their Ni-H conditions in the presence of allyl benzyl ether 13 gave only a complex mixture with traces of the desired product (as judged by GC/MS). In parallel to this study, a control reaction was done with an example from the same reference confirming its reproducibility in our hands (see SI for details). Similarly, using the conditions reported in ref. 26 that were developed for a-amino acids with a-acetoxy RAE 14 and two different organozinc reagents 11 resulted in either low conversion (X = I , <5%) to product with mostly recovered 14 (as judged by GC/MS) or low yield and ee (X = Cl•LiCl, 14% yield, 6% ee). As these existing methods all gave unsatisfactory results, extensive screening of various reaction parameters, including nickel source, chiral ligands, additives, solvent and reaction temperature was iteratively conducted to arrive at the optimal conditions. Under the final protocol, TCNHPI-based RAE 10 and alkyl zinc reagent 11 were smoothly cross-coupled in the presence of NiCl2•glyme and chiral bis-oxazoline ligand L1, affording dialkyl acetate 8 in 64% isolated yield and 92% ee (Table , entry 1). In striking contrast, NHPI-based RAE 14 proved to be much less effective (11% yield, Table , entry 2). An array of other chiral ligands was inferior to L1 in terms of yield and asymmetric induction (Table , entry 3-9). Control experiments indicated that nickel catalyst and ligand were both crucial to promote this reaction (Table , entry 10-11). In terms of additive, TMSCl was found to be beneficial for improving the yield, which was consistent with G.C. Fu's observation, but unlike their report, it essentially had no influence on the ee value (Table , entry 12). Furthermore, a small loss in efficiency was observed when the reaction was conducted at 0 o C or under air (