Palladium‐Catalyzed Cross‐Coupling Strategy for (6S)‐Aryl‐Pyran‐3‐ols: Synthesis, ADMET Profiling, and Molecular Docking Studies

ABSTRACT C‐glycosides are attractive scaffolds with remarkable hydrolytic stability and therapeutic potential, yet their stereoselective synthesis remains challenging. Here, we report a palladium‐catalyzed cross‐coupling strategy for the efficient synthesis of α‐C‐glycosides and (6 S )‐substituted‐3,6‐dihydro‐2 H ‐pyran‐3‐ol derivatives from 3,4‐O‐carbonate L‐arabinal and diverse potassium aryltrifluoroborates. The reactions proceed under mild conditions at room temperature, delivering products in excellent isolated yields (79%–92%) with high stereochemical integrity, as confirmed by 1 H/ 1 3 C NMR, HRMS, and optical rotation analyses. The method tolerates a wide range of electron‐donating, electron‐withdrawing, and heteroaryl substituents, providing a structurally diverse library of aryl‐substituted pyran derivatives. In silico ADMET profiling using SwissADME, BOILED‐Egg, and ProTox‐II indicated favorable pharmacokinetic properties, including predicted human intestinal absorption, low toxicity, and, in several cases, blood–brain barrier penetration. Molecular docking studies against Mitogen‐activated protein kinase 14 (MAPK14/p38α) revealed strong binding affinities for compounds 8 , 13 , 14 , and 15 , supported by key hydrogen‐bond and π–π stacking interactions comparable to the reference inhibitor SR‐318. MMGBSA calculations confirmed stable binding free energies, indicating enhanced target engagement. These findings highlight the potential of (6 S )‐aryl‐substituted pyran‐3‐ol derivatives as promising scaffolds for the design and development of novel anti‐inflammatory or anticancer agents and demonstrate the power of integrating synthetic chemistry with computational prediction for drug discovery.