Molecular Iodine-Catalyzed Synthesis of 3,3-Disubstituted Isatins: Total Synthesis of Indole Alkaloid, 3,3-Dimethoxy-2-Oxindole

3,3-Dialkoxy-2-oxindoles are prevent in natural product family and exhibit unique biological activities. Among them, acyclic alkoxy analogues shows instability toward acidic conditions, making the access to acyclic isatin ketals highly challenging. Conventional methods for the synthesis of 3,3-dialkoxy-2-oxindoles usually require strong acid and harsh reaction conditions, resulting in low overall efficiency. Herein, we report the acid- and metal-free protocol for the synthesis of 3,3-dialkoxy-2-oxindoles from isatins through an iodine-catalyzed ketalization. This protocol does not require the use of any specific reagents including metal-catalysts. Furthermore, the total synthesis of the unprecedented 2-oxindole alkaloid bearing 3,3-dimethoxy moiety has been achieved.