Exploiting Natural Complexity: Synthetic Terpenoid-Alkaloids by Regioselective and Diastereoselective Hydroaminoalkylation Catalysis

We report a catalytic and atom-economic approach for the addition of N-methyl groups to unactivated alkene-containing terpenes to generate a library of synthetic terpenoid-alkaloids. This catalysis was accomplished using Ta(CH₂SiMe₃)₃Cl₂ in combination with a new chiral ureate salt for highly chemo-, regio-, and diastereoselective hydroaminoalkylation reactions. The desired products are easily isolated and purified from unreacted starting materials to give aminated terpenes in one catalytic step. Starting material enantiopurity is completely retained, and stereoselective catalysis results to give enantiopure products. Absolute stereochemistry was determined by X-ray crystallography and is consistent with regio- and stereoselective alkene insertion into a catalytically active tantallaziridine intermediate.