Merging of Two Photoredox Cycles with One Perovskite Catalyst Achieving Dual Functionalization: N-Heterocyclization and Site-Selective Bromination of N-Arylamines

Abstract

Dual functionalization in organic synthesis represents a powerful strategy aimed at achieving multiple transformations within a single reaction cycle, thereby streamlining synthetic processes, enhancing efficiency, and imparting economic paths for complex molecules. Here, we report a heterogeneous perovskite nanocrystal (NC) photocatalytic system that can simultaneously drive two photoredox cycles in a single reaction. The dual process incorporates two distinct functional groups (N-heterocycles and bromines) into N-arylamines under the influence of a single catalyst (CsPbBr₃ NCs), allowing for the concurrent formation of two distinct architectures of 3-bromo-N-arylindoles. Mechanistically, long-lived charge separation and charge carrier accumulation at the NC surface enable perovskite to drive these two photoredox cycles simultaneously. The dual approach exploits light-induced holes to drive an amine oxidation in one cycle (I) and cooperatively utilizes dibromomethane (CH₂Br₂), a solvent-grade mild reagent for site-selective bromination, to achieve the other photoredox cycle (II). We find that chiral perovskite induces enantioselective axial C-N bond formation, but is inactive for axial C-C bond formation of arylindoles. Merging two photoredox cycles simultaneously to achieve dual functionalization is rare; thus, the perovskite NC photocatalysis not only aligns with the principles of green chemistry but also holds immense potential for the rapid and economical design of complex molecules.

Scheme 1.. Photoredox Cycle Coupled with (a) Organocatalysis, (b) Transition Metal Catalysis, (c) Biocatalysis, and (d) Our Work with Another Photoredox Cycle

Scheme 2.. Reaction Scope^a

^aConditions: NCs (1 mg), mixed solvent, blue LED at room temperature, d.r. (diastereoselective ratio, based upon ¹H NMR).

Scheme 3.. Derivatization of the Dual Functionalization Product

Scheme 4.. Enantioselective Exploration of 2a, 2k, and 2q

Scheme 5.. Proposed Mechanism for N-Heterocyclization and Subsequent Bromination of Indole