Chiral a-amino ketones represent valuable building blocks serving as key intermediates for the synthesis of a vast array of natural products and medicines. 1 Thus far, the most common retrosynthetic disconnections involve classic 2e-based disconnections relying on either a-amination strategies or the homologation of chiral pool-derived aamino acids. For instance, building block 1 (Figure ), an intermediate used for the synthesis of ACE inhibitors has been constructed via the latter strategy from L-phenylalanine in 6-8 steps 4 wherein most of the reaction steps do not forge strategic bonds resulting in low ideality. In principle, a far more direct means of accessing 1 would employ a radical retrosynthetic strategy wherein the redox active ester (RAE) of phenylalanine (2, racemic or enantiopure) could be combined with the simple succinate derivative 3 through an enantioselective decarboxylative acylation. Forging Cacyl bonds through radical cross coupling is not new. As shown in Figure , three basic strategies have been reported for the construction of a-chiral ketones through In the first of these (Strategy A), an alkyl halide 8 or dihydropyridine motif serves as a radical precursor for reductive (chemical or photochemical) activation before entering the Ni-catalytic cycle and reacting with an activated acyl group. In the second strategy (B), photoinduced HAT of labile C-H bonds (benzylic or adjacent to a benzamide) leads to the requisite radical donor. The final strategy (C) uses a terminal olefin input in a three component coupling with a chloroformate and suitable radical donor. Building on these pathpointing disclosures, the targeted transformation to access 4 was explored as shown in Figure using 2 and 3. Unfortunately, as the aforementioned methods (Strategy A) were largely developed using alkyl halides, applying these conditions to substrates 2 and 3 all gave unfruitful results with only trace quantities of 4 observed (Figure ). It is worthing noting that RAE 2 was fully consumed under the conditions of Reisman and co-workers 8a while it largely remained intact using the protocols of Wang 8b and Chen. 8c Herein a highly enantioselective and general Ni-catalyzed decarboxylative acylation is described that can deliver 68% yield (92% ee) of 4 through a simple protocol that can be used repeatedly to simplify the synthesis of such structures. Optimization studies began with the reductive decarboxylative acylation of RAE 2 and acid chloride 3 (Table ). Extensive investigation revealed that the final optimal conditions utilized NiCl2•glyme (10 mol%), a commercially available chiral ligand L9 (15 mol%) and Mn powder (3.0 equiv) in CH3CN/DME (1:1, 0.1 M) at room temperature for 5 h, affording ketoester 4 in 68% isolated yield and 92% ee. An in situ activation protocol offered comparable reaction efficiency (entry 1). Numerous reaction paramters were examined, some of which are summarized in Table . Using Ni(acac)2 as the nickel source significantly diminished the reaction efficiency (entry 2). Surprisingly, replacing Mn with Zn as reductant completely failed to provide any product (entry 3). An unusual solvent choice proved to be extremely critical to both reactivity and asymmetric induction, with a 1:1 mixture of CH3CN and DME proving superior to a single solvent (entries 4-5). A wide variety of chiral ligands were also tested (entries 6-12), and chiral bis(oxazoline) ligands (L1, L2, L8, L9) generally gave higher yield and ee than other types of chiral ligands (L4-L7), which was consistent with previous reports. A fine-tuning of the steric properties of BOX ligands showed that L9 was optimal. Control experiments indicated that essentially no detectable product formed when reactions were conducted without nickel catalyst or chiral ligand (entries 13-14). The reaction was not very sensitive to oxygen because only a slight loss of yield was observed when the reaction was conducted under air in a capped vial, although the deliberate addition of water (1.0 equiv) significantly reduced the reaction efficiency (entries 15-16). Other acyl surrogates, including in situ activation protocols (entries 17-18) and an isolated thioester precursor (entry 19), did not produce any product. In all cases, both starting materials 2 and 3 were mostly recovered. With a concrete set of conditions in hand, the generality of the substrate scope was evaluated, as depicted in Table . A broad array of acid chlorides derived from primary carboxylic acids were tested, delivering the desired chiral a-amino ketones in moderate to good yields and with excellent enantioselectivity. Aside from simple alkyl chains (5, 6, 9, 13, 16, 18 and 19), a wide range of functional groups could be tolerated, such as alkyl halides (7, 8), esters (10), terminal alkenes (11), ethers (12, 14), internal alkenes (21, 22), ketones (23, 24), electron-rich aromatic rings (15, 20), and aryl bromides (25). Acid chlorides derived from secondary carboxylic acids and aromatic acids were also suitable coupling partners (16, 17, 19, 25 and 26), providing desired products in moderate yields and excellent enantioselectivity. Various redox-active esters derived from easily accessible a-amino acids (racemic or enantiopure) were also applied in this enantioconvergent coupling reaction (products 5-14, 16, 17, 21, 27, 30, 34, 35 and 38-42 were derived from racemic RAEs while 15, 18-20, 22-26, 28, 29, 31, 32, 33, 36 and 37 were synthesized from L-a-amino acids-derived RAEs). Besides RAEs bearing simple alkyl chains (27, 28, 30, 31, 35, 36 and 37), those with functional groups such as thioethers (29), carbamates (32), esters (33), terminal alkenes (34), aryl halides (38, 41), trifluoromethyl groups (40) and heterocycles (42), could be smoothly coupled with acid chlorides. The benzoyl substituents on the amino position also could be varied (38-42). Diastereoselectivity can be highly controlled by chiral ligands rather than the pre-existing stereocenters such as in the cases of substrates 23, 24, 36 and 37. With the exception of compounds 17, 23, 24, 26 and 28, none of these structures have been prepared before either in racemic or enantioenriched form. With regard to limitations, switching the protecting groups from Bz to Boc or phthalimide led to considerable loss of ee (43, 44). a-Chloro acid chlorides and tertiary acid chlorides were not competent coupling partners under current optimal conditions (45, 46). The developed chemistry outlined herein can have a tangible simplifying impact on the synthesis of seemingly simple structures as shown in Figure . For instance, compound 1 (Figure ) was previously accessed in 6-8 steps using polar bond analysis requiring numerous protecting groups, functional group interconversions, redox manipulations, and pyrophoric reagents. In contrast, this method enables single step access through enantioselective decarboxylative acylation of 2 with 3 followed by hydrolytic workup. The enantiopure allylated a-amido-ketone 56 (Figure ) was