Iron‐Catalyzed Asymmetric [4+2]/Cheletropic Retro‐[4+1] Cycloadditions of Thiophene S,S‐Dioxides with 3‐Substituted Indoles

Abstract The Diels–Alder/cheletropic retro‐[4+1] cycloadditions of thiophene S , S ‐dioxides are a prominent method for synthesizing unsaturated six‐membered carbocycles. However, to the best of our knowledge, catalytic asymmetric variations of these reactions have not yet been achieved. Herein, we report Fe(III)‐bis(oxazoline) complex‐catalyzed inverse‐electron‐demand [4+2] cycloaddition/cheletropic retro‐[4+1] extrusion of SO 2 reactions between thiophene S , S ‐dioxides and 3‐substituted indoles. The key to the success of this transformation involves using thiophene S , S ‐dioxide components bearing an N ‐acyloxazolidinone group at the C2 position, which coordinates with the chiral catalyst, and a halide group at the C5 position to prevent the self‐dimerization of thiophene S , S ‐dioxides. Computational studies revealed that the [4+2] cycloaddition proceeds via a stepwise mechanism, with the subsequent retro‐[4+1] cycloaddition acting as a driving force to facilitate the initial [4+2] cycloaddition. This [4+2]/cheletropic retro‐[4+1] cycloaddition reaction sequence enables the synthesis of a broad range of hexahydrocarbazoles bearing a quaternary stereogenic center, which are core structures in numerous families of indole alkaloids, in good yields with high enantioselectivities. The synthetic utility of this method is demonstrated through diverse product transformations and a concise, enantioselective total synthesis of (+)‐geissoschizoline.