An efficient transition metal-free indolylation on 6-chloropurine ribonucleosides and photophysical studies of conjugated nucleosides

Abstract

Herein, we report an efficient transition-metal-free approach for C–C bond formation on modified nucleosides via two complementary pathways: (i) a Lewis acid-mediated protocol employing AlCl₃, and (ii) a Brønsted acid-mediated approach using trifluoroacetic acid (TFA). Among these, the TFA-HFIP system emerged as the optimal condition for regioselective C6-heteroaryl functionalization of 6-chloropurine nucleosides through direct coupling with diverse indole derivatives. To demonstrate the synthetic versatility of this methodology, a benzenesulfonamide-conjugated 1,2,3-triazole hybrid nucleoside was synthesized and subsequently explored Suzuki coupling and N-arylation to afford purine-fused polycyclic nucleosides. Photophysical studies revealed that the hybrid nucleoside 14 exhibits significantly enhanced fluorescence relative to the parent compound 11n, while the highly conjugated derivatives 15 and 17 show pronounced photophysical properties.