Scheme 1.

Synthesis of capless HDACi 6 a–i. Reagents and conditions: i) 1 (1.0 equiv.), anhydrous KOAc (2.0 equiv.), PdCl₂(dppf) (0.05 equiv.), bis(pinacolato)diboron (1.2 equiv.), anhydrous DMF (15 mL), 80 °C, 18 h, 33 %; ii) 1 (1.0 equiv.), R¹‐B(OH)₂ (1.1 equiv.), Pd(PPh₃)₄ (0.05 equiv.), toluene, Na₂CO₃ solution (2 M), EtOH, reflux, 16 h, 49–76 %; iii) 2 (1.0 equiv.), anhydrous Cs₂CO₃ (2.0 equiv.), PdCl₂(dppf) (0.05 equiv.), 2‐bromopyridine (3.0 equiv.), anhydrous DMF, 85 °C, 16 h, 53 %; iv) 3 a–i (1.0 equiv.), Pd(C) (5 %) (0.1 equiv.), H₂, MeOH/DCM (75 : 25; v/v), rt, 2–16 h, 81 % quant.; v) 4‐acetamidobenzoic acid (1.2 equiv.), EDC ⋅ HCl (3.0 equiv.), HOBt ⋅ H₂O (3.0 equiv.), DIPEA (5.0 equiv.), 4 a–i (1.0 equiv.), dry DMF/dry DCM (67 : 33, v/v), rt, 16 h, 38–81 %; vi) 5 a–i (1.0 equiv.), DCM/TFA (80 : 20; v/v), 0 °C→rt, 1–3 h, 62 % – quant.