Regio- and Enantioselective Aza-Diels-Alder Reactions of 3-Vinylindoles: A Concise Synthesis of the Antimalarial Spiroindolone NITD609

An asymmetric aza-Diels-Alder reaction of 3-vinylindoles with isatin-derived ketimines has been developed. A series of spiroindolone derivatives were thus obtained in good to excellent yields with excellent enantioselectivity (up to 96% yield and 99% ee). Furthermore, the antimalarial compound NITD609 could be obtained in three steps with an overall yield of 40.6%. Control experiments and operando IR experiments imply a concerted reaction pathway. The regioselectivity and exoselectivity result from - interactions between the two indoline rings of the two reactants.