The present study demonstrates an in-silico-assisted approach to design triarylboranes that exhibit promising reactivity as main-group catalysts for the reductive alkylation of amino acids with H2. We constructed an in-silico library of triarylboranes, including 46 unprecedented boranes, and obtained their theoretical parameters using DFT calculations. We initially synthesized seven of these unprecedented boranes to confirm their reactivity under the chosen model reaction conditions. Guided by Gaussian process regression using these theoretical and experimental parameters, we subsequently synthesized three more boranes and identified the optimal triarylborane, i.e., B(2,3,5,6-Cl4-C6H)(2,6-F2-3,5-(CF3)2-C6H)2 (B 4b ). Through the evaluation of the regression-based models, we confirmed that the deformation energy (EDEF) may serve as a potentially useful parameter to construct an adequate model, while the use of LUMO energy levels tends to lead to an underestimation when predicting the catalyst activity (TOF in h -1 ) under the model reaction conditions. We also identified that 4-methyltetrahydropyrane (MTHP) is a superior Lewis-basic solvent for not only the generation of FLP species with B 4b , but also for the realization of a more practical and sustainable reaction system compared to a system using THF. In fact, the B 4b -catalyzed reductive alkylation using aldehydes as an alkylating reagent and H2 in MTHP proceeded efficiently even in the presence of a variety of additives, showcasing its broad functional-group compatibility. Aniline-derived amino acids and C-terminal-protected peptides were alkylated in good-to-excellent yields under the optimized conditions with the concomitant generation of H2O as the sole byproduct, demonstrating the significant advancement in terms of practicality and sustainability for the main-group-catalyzed reductive functionalization of valuable amines using H2.