Sulfonamidation of Aryl and Heteroaryl Halides through Photosensitized Nickel Catalysis

Abstract

Herein we report a highly efficient method for nickel-catalyzed C–N bond formation between sulfonamides and aryl electrophiles. This technology provides generic access to a broad range of N-aryl and N-heteroaryl sulfonamide motifs, which are widely represented in drug discovery. Initial mechanistic studies suggest an energy-transfer mechanism wherein C–N bond reductive elimination occurs from a triplet excited NiII complex. Late-stage sulfonamidation in the synthesis of a pharmacologically relevant structure is also demonstrated.

General Paradigm in Photoredox Nickel‐Catalyzed Cross‐Coupling Allows for Light‐Free Access to Reactivity

“…Our results show that Ni‐catalyzed amination, etherification, and esterification of aryl bromides can all be realized across a wide range of substrates without light under conditions that otherwise bear resemblance to the parent photochemical methodologies. To this end, one may wish to re‐evaluate the growing body of literature that invokes energy transfer as the mechanism for catalysis . As we show here, only a small amount of Ni I can initiate self‐sustained Ni I /Ni III thermal catalysis.…”

“…Given the similarity of conditions employed across Ni photoredox cross‐coupling methodologies, we hypothesized that this strategy of using a heterogeneous reducing agent to thermally access and sustain a Ni I/III cycle may be generalized to other nucleophiles. As shown in Entry 1 of Table , we obtained the expected cross‐coupled product in the reaction between methanol and 4′‐bromoacetophenone by using only 0.01 equivalents of Zn 0 and 1 mol % (dtbbpy)NiCl 2 (dtbbpy=4,4′‐di‐ tert ‐butyl‐2,2′‐dipyridyl) prepared in situ from (dme)NiCl 2 and dtbbpy.…”

Hypervalent Iodine Mediated Sulfonamide Synthesis

“…1 1-(Phenylsulfonyl)indoline (3ak): [26] Prepared according to the general procedure. 1 [28] Prepared according to the general procedure. Purification by thin layer chromatography using ethyl acetate/ hexane (1:3) gave the title product as a light-brown solid in 51 % yield.…”

Photochemical Strategies for Carbon–Heteroatom Bond Formation

“…More recently, the same transformation was realized using organic sensitizers and heterogeneous photocatalysts, such as graphitic carbon nitrides and lead halide perovskites . A similar mechanistic scenario was proposed for the N ‐arylation of sulfonamides, sulfoximines, and carbamates …”