No abstract

Nucleosides have important therapeutic applications that include antiviral activities against COVID viruses. It is a common strategy to convert one or multiple of the hydroxyl (OH) units in nucleosides to the corresponding ester groups to prepare nucleoside prodrugs for better performance. Due to the presence of multiple OH units in nucleosides, current protocols for access to such ester prodrugs involve multiple steps due to installation and removal of protection groups. Here, we disclose a catalytic strategy that allows for regioselective functionalization of a specific OH unit without the need of protecting other OH groups. The key step in our method is an N-heterocyclic carbene-catalyzed selective acylation of the pentose unit of nucleosides. We demonstrate that commercially launched COVID-19 prodrugs such as molnupiravir can be prepared in concise routes by using our strategy.

A catalytic regioselective addition reaction of oxindoles with ynals is developed. Allene-containing derivatives bearing various substituents and substitution patterns are afforded as the products in generally moderate to good yields with moderate diastereoselectivities. Several of allenes obtained from this protocol are valuable in the development of novel bactericides for plant protection.

An acid-catalyzed 2-alkylation of indole molecules is developed. Only catalytic amount of the commercially available, inexpensive and traceless HI is used as the sole reaction promoter. 2,3-Disubstituted indole molecules bearing congested tertiary carbon centers are afforded as the final products in moderate to excellent yields.