The reaction is also amenable to heterocoupling (Table ) to facilitate the rapid conversion of inexpensive natural AAs (glutamic acid and aspartic acid) into valuable unnatural AAs (of either absolute stereochemistry) without racemization (See Fig. and S8 for the confirmation of no racemization). Although 3-6 equiv of coupling acid is needed to achieve synthetically useful yield, all the reagents as well as starting materials are inexpensive. Despite its simplicity and obvious utility, Kolbe heterocoupling of AAs has been a formidable challenge for conventional Kolbe reaction, and the rAP-based method exhibits broadest reaction generality thus far. For instance, lipophilic non-canonical side chains for 20 (ca. $50/g) and 21 (ca. $520/g) are readily accessible. Yet, a direct one-step access from readily available starting material did not exist, and the most common ways of accessing such structures involve resolution, biocatalysis, asymmetric hydrogenation, and chiral auxiliary/chiral pool chemistry (see Supporting Information for a graphical compilation of prior approaches). Trifluoronorleucine (22, ca. $5000/g) is a fluorinated analog of norleucine, and its only published enantioselective synthesis requires a stoichiometric amount of a chiral nickel complex. Olefin-containing AA 23 is a key building block to construct antiviral agents. Despite its importance, it is prohibitively expensive (ca. $1000/g) for practical use, and the previous syntheses require laborious preparation of a key intermediate prior to asymmetric hydrogenation or a bespoke ligand for asymmetric coupling. 24 is an example of phenyl alanine homologue that is useful for SAR study. Homolysine 25 (ca. $1600/g) is a useful analog of lysine for fine-tuning peptide side chains, and α-aminopimelic acid 26 (ca. $5000/g) has documented bioactivity. Ketone-containing unnatural AA 27 (ca. $5000/g) is found in bioactive cyclic tetrapeptides (HDAC inhibitors). Direct access to 25-27 has been elusive thus far, resorting to numerous indirect 2e -strategies such as cross metathesis from an unnatural amino acid, chiral auxiliary-based α-amination of a carboxylic acid or repurposing of chiral pool materials such as Garner's aldehyde 46 or glutamic acid. Although functional group tolerance was markedly improved by using rAP, redox-sensitive functionalities such as terminal alkynes (28), alkyl halides (29) as well as heterocycles (30, 31) are not well tolerated (Table ).