The retrosynthetic simplification enabled by this enantioselective decarboxylative Negishi coupling (EDCC) is further demonstrated by six real-world applications in synthetic chemistry. Broadly speaking, the vast majority of approaches to such compounds take advantage of reliable asymmetric epoxidation techniques followed by nucleophilic openings (Strategy A, Figure ). The first four examples, illustrated in Figure , all follow this pattern. For instance, the preparation of compound 67 (Figure ), an intermediate used in the total synthesis of Calonyctin A2, required an 11-step sequence wherein only one of those steps forged a C-C bond. Six of the remaining steps were dedicated to access enantiopure epoxide 63 from L-glutamic acid 62 and four steps involved protecting and functional group manipulations. In contrast, commercially available 2-hydroxypentanoic acid 65 was smoothly transformed to desired carbinol 67 in only 2 steps after an O-protection/acid activation and EDCC (53% yield, 91% ee). Next, epoxide-based strategy A was again applied to synthesize dialkyl carbinol 73 (Figure ), an intermediate used in the total synthesis of Centrolobine, requiring a 9-step procedure with only one C-C bond formation reaction. The current strategy could considerably simplify that route, commencing with an a-hydroxylation of 5-hexenoic acid 71, O-protection/acid activation, EDCC (48% yield, 95% ee), and a one-pot ozonolysis/reduction. EDCC could be applied to even more complex target molecules such as lactone 78 which served as a key intermediate in the total synthesis and structural revision of Rubrenolide (Figure ). Previously, a 14-step synthetic sequence from decane-1,10-diol 74 was required. However, only 2 of those steps formed C-C bonds, with the remainder dedicated to protecting group chemistry and redox manipulations. Chirality was introduced by a venerable Sharpless AE (strategy A). Enabled by the EDCC strategy outlined above, commercially available H-DL-Glu(OMe)-OH 76 was first converted to corresponding a-hydroxy acid and then subjected to the general procedure to afford cross-coupled product in 64% yield and 85% ee. Further elaboration involving global hydrolysis and acid-promoted lactonization uneventfully provided lactone 78 in five overall steps. Finally, Chiral aldehyde 83 bearing a Boc-protected proline moiety was previously synthesized in 8 steps through strategy A, with two of them forming C-C bonds (Figure ). In contrast, commercially available 2-hydroxyhexanoic acid 81 could be converted to the same product in only three steps via two simple condensation reactions, followed by a one-pot EDCC/acidic deprotection (41% yield, > 20:1 dr.). sequences (Figure ), commercially available a-hydroxy acid 6 (racemic, $7/g) was converted to the same product in merely 2 steps via an O-protection/acid activation, followed by an EDCC/in situ deprotection (68% yield, 92% ee). The simple lactone 84 (a commercial product), an important constituent in cheese and butter having a sweet, creamy and milky odor, is an interesting case for analysis as it has been prepared at least nine different ways as summarized in Figure . The strategies range in step count from ca. 3-23 with reliance on epoxide opening (twice), 33 chiral pool/refunctionalization (twice), 34 allylic substitution with an expensive Ir-catalyst, Sn-based Keck allylation, vinylogous aldol, and various enzymatic reactions (twice). The current EDCC approach can be leveraged to enable rapid access to 84 in high ee and on gram-scale.