A Ni–Ir Dual Photocatalytic Liebeskind Coupling of Sulfonium Salts for the Synthesis of 2‐Benzylpyrrolidines

Abstract

A new method has been developed for the synthesis of 2‐benzylpyrrolidines utilizing cross‐coupling and photoredox catalysis. Using a well‐established dual Ni–Ir system, we were able to successfully couple benzylsulfonium salts with proline utilizing radical forming through CO2 extrusion. This enabled the simple one‐step synthesis of 2‐benzylpyrrolidines from stable, inexpensive starting materials.

Radical C−C Bond Formation using Sulfonium Salts and Light

“…The salts were prepared from the corresponding benzyl bromides 16 by a simple substitution reaction (Scheme ) . To increase the stability of these salts, the bromide counter ion can be exchanged for hexafluorophosphate …”

“…Building on this work, Novák and co‐workers recently reported a metallaphotoredox coupling of benzylsulfonium salts 18 with N ‐Boc‐protected prolines (Scheme ) . Various electron‐deficient and electron‐rich benzylsulfonium salts underwent cross‐coupling to provide the desired products in moderate to good yields ( 20a–d ).…”

Photocatalytic Palladium-Catalyzed Fluoroalkylation of Styrene Derivatives

“…In continuation of our studies in the field of fluoroalkylation reactions 3a , 3b , 10 and photocatalytic transformations, 11 we aimed to take advantage of the photo-Heck-type coupling approach to introduce more versatile fluoroalkyl groups into the styrene moiety using palladium catalysis and visible light irradiation ( Scheme 1 ). The classical palladium catalyzed cross-coupling reaction 12 involves a well-established two-electron redox mechanism typically between the Pd(0)/Pd(II) oxidation states.…”

Shining Light on C−S Bonds: Recent Advances in C−C Bond Formation Reactions via C−S Bond Cleavage under Photoredox Catalysis

“…As discussed above, the construction of C−C bonds from various fluoroalkyl radicals generated via visible light induced C−S bond cleavage has been well studied. Nevertheless, there are only a few examples for generating alkyl radicals to construct C−C bonds through photoredox catalyzed desulfurative approaches from sulfonium salts [26–27] and sulfones, [43] respectively. In this context, in 2018, Qin group found that N ‐acyl alkylsulfinamides 213 could be used as alkyl radical precursors through visible light mediated desulfuration [44] .…”

“…In addition, using a well‐established transition metal‐photoredox dual catalytic system, Novák group [27] developed a new method for the synthesis of 2‐benzylpyrrolidines through the cross‐coupling of benzylsulfonium salts with proline. Co‐catalyzed by Ni(glyme)Cl 2 and Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 , various benzyl sulfonium salts 116 could couple with N ‐Boc‐proline 117 to produce the desired benzylpyrrolidine products 118 under blue LED irradiation (Scheme 23).…”