Indole dearomative [3,3]-Claisen rearrangement: access to indole alkaloids with C2/C3 quaternary stereocenters

Polycyclic indole alkaloids bearing a C2 and/or C3 quaternary stereocenter feature diverse skeletons and promising biological activities, rendering them important targets in natural product synthesis and medicinal chemistry. A central synthetic challenge in preparing these molecules lies in the efficient construction of the C2 or C3 quaternary stereocenter. The indole dearomative [3,3]-Claisen rearrangement enables the facile assembly of the C2 or C3 quaternary stereocenter of indole, exhibiting excellent stereospecificity, broad functional group tolerance, and versatile product architectures. This transformation has been extensively exploited in the total synthesis of complex indole alkaloids. In this review, we classify indole dearomative [3,3]-Claisen rearrangements into four categories based on substrate types and systematically summarize their synthetic applications in natural product synthesis over the past five decades.