The unique property of chiral aldehyde catalysis, directly promoting the asymmetric functionalization of Nunprotected amino acid esters, has been demonstrated in alkylation, Michael addition, Mannich, aldol, allylation, benzylation, and propargylation reactions. We envisioned that this strategy may be promising for the direct asymmetric hydrocarbylation of amino acid esters with halohydrocarbons. However, it was challenging to control the chemoselectivity of C/N-functionalization in this transformation. In the previously reported reactions employing chiral aldehyde catalysis, either the electrophiles were gradually generated in situ during the reaction process (for alkylation, allylation, benzylation, and propargylation reactions), or the N-functionalization side products were unstable and reversely decomposed to starting material (for Michael, Mannich, and aldol reactions). Therefore, the side reaction of N-functionalization in those reactions was efficiently suppressed. In our proposed reaction, chiral aldehyde-catalyzed hydrocarbylation of N-unprotected amino acid esters with halohydrocarbons, the equivalent amounts of halohydrocarbon electrophiles and the possible formation of stable N-hydrocarbylation byproducts made chemoselectivity more difficult to control. Thus, it was necessary to develop an aldehyde-catalyzed direct hydrocarbylation reaction of amino acid esters with improved chemoselectivity and enantioselectivity. In this work, we report on three chiral aldehyde-catalyzed asymmetric substitution reactions of N-unprotected amino acid esters with aryl halides, allyl chlorides, and benzyl chlorides. Although the N-functionalization byproducts are not suppressed completely, the de-sired C-functionalization products can be generated in moderate-to-high yields with good-to-excellent enantioselectivities for all three transformations. Furthermore, the arylation product is used for the formal total synthesis of the clinical candidate compound (+)-AG-041R, and three reaction models are proposed based on the results of control experiments and density functional theory (DFT) calculations.