Diastereoselective Access to Tetracyclic Eight‐Membered Lactams through a Dearomative Heck Reaction and an Alkylative Ring‐Opening Driven by Photoexcited Spiroindolines

Abstract

An external‐photocatalyst‐free, light‐driven alkylative ring‐opening of stable spiroindolines was developed to construct indolo‐ and benzoannulated eight‐membered lactams. The spiroindolines were prepared from tetrahydro‐β‐carbolines by a dearomative Heck reaction. Mechanistic experimental studies on the alkylative ring opening suggested that a photoredox pathway was involved, in which the spiroindoline performed as both reagent and photosensitizer. DFT calculations showed that the radical addition toward a cyclic alkene was the key to the diastereoselective formation of tetracyclic medium‐sized lactams.

Kinetic Resolution of Spiroindolines through Ir-Catalyzed Asymmetric Allylative Ring-Opening Reaction

“…However, to date, there has been no report of the simultaneous construction of chiral indole-containing medium-sized rings and spiroindolines in a single transformation. Inspired by the work contributed by You’s group and Carreira’s group in which alkenes behave as benign nucleophiles in Ir-catalyzed AAA reactions as well as in connection with our previous findings on a photodriven diastereoselective alkylative heterolytic fragmentation of spiroindolines 1 , a type of dearomative Heck reaction products of tetrahydro-β-carbolines, we envisioned a kinetic resolution strategy for accessing chiral indole-annulated eight-membered lactams featuring two contiguous stereogenic centers and one axis together with spiroindolines featuring an α-tertiary amine (Scheme ). Racemic spiroindoline 1 may selectively react with a chiral Ir-allyl species to deliver a tertiary cation, which proceeds via a C–C bond fragmentation followed by an alcohol trapping to afford a medium-sized lactam .…”

“…To demonstrate the utility of the kinetic resolution, we attempted chemical transformations of enantiopure spiroindoline 1a and lactam 2aa (Scheme ). ,, As illustrated, a substrate-controlled diastereo- and enantioselective alkylative ring-opening reaction of R - 1a was performed under the photoirradiation condition, providing lactams 3 and 4 in good yields and >99% ee. The absolute configuration was established as R , S a by X-ray crystal analysis of enantiopure 4 .…”