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. Tantalizing complexity: an in situ Ta‐catalyzed method for hydroaminoalkylation using naturally occurring terpene substrates to generate terpenoid‐alkaloid products is reported. This reaction uses alkyltantalum precursors in combination with modular urea ligands for highly regio‐ and diastereoselective transformations. Products can all be purified using a simple filtration protocol, and crystallography data confirms the formation of a single diastereomer and no racemization of enantioenriched terpene substrates.