Studies Toward the Total Synthesis of Stenine

Nucleophilic carbenes have recently emerged as powerful 1,1-dipole equivalents for the construction of functionalized hydroindolone derivatives via a novel [4+1] cycloaddition with vinyl isocyanates in our laboratory. This methodology has been successfully used in the total synthesis of several alkaloids, such as tazettine and mesembrine. Currently, we are investigating the total synthesis of stenine (1), a member of Stemona alkaloids which are isolated from the root extracts of Stemona species of plants. Our synthetic strategy involves the assembly of hydroindolone 4 by using [4+1] cycloaddition of vinyl isocyanate 2 and bis(alkylthio)carbene 3. Another key transformation of our approach is to install the 7-membered ring moiety of the azepinoindole on highly functionalized hydroindolone via a 7-endo trig radical cyclization (5→6). Current efforts are directed toward preparing advanced intermediate 5 and further elaborating it to stenine (1).