Site‐Selective CH Amination of Lupane‐Type Triterpenoids

A synthetic protocol for rhodium‐catalyzed, site‐selective CH amination of the betulin scaffold has been developed. Under catalytic conditions, betulin‐derived 28‐ O ‐sulfamate ester undergoes intramolecular CH amination to afford 1,2,3‐oxathiazinane‐2,2‐dione‐fused lupane triterpenoids with a C16/C22 selectivity ratio 9:1. Introduction of a C16‐substituent enables a second sequential CH amination, which occurs with C22 selectivity. Betulin‐derived oxathiazinanes can be cleaved and the ring‐opened products provide straightforward access to 16‐amino‐ and 16‐azido‐betulin, 16‐amino‐betulinic, and 16‐amino‐betulonic acids. Betulin analogs with selectively introduced amine and azide functionalities are versatile building blocks for further medicinal chemistry applications in semisynthetic triterpenoid series.