Redox-Activated Amines in C(sp³)–C(sp) and C(sp³)–C(sp²) Bond Formation Enabled by Metal-Free Photoredox Catalysis

Abstract

The amino group represents one of the most prevalent structural motifs in organic chemistry. Therefore, application of amines as alkylating agents in synthesis is highly compelling. Herein, we present a metal-free photoredox strategy for the formation of C(sp 3 )−C(sp) and C(sp 3 )−C(sp 2 ) bonds from redox-activated primary amine derivatives. The developed reaction of 2,4,6-triphenylpyridinium salts with alkynyl ptolylsulfones, leading to functionalized alkynes, is easily scalable and offers broad substrate scope, high chemoselectivity, and mild conditions. Its potential is also highlighted by diversification of complex molecular scaffolds. Additionally, the approach is also suitable for synthesis of (E)-alkenes from vinyl phenyl sulfones. Mechanistic studies contribute to the elucidation of unexpected differences in reactivity of primary and secondary alkyl substituted pyridinium salts.

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…Reviews reactions proceed in good yields with aw ide range of substrates;h owever,p rimary N-alkyl pyridinium salts necessitate the addition of triethylamine and slightly increased temperatures to achieve product formation in moderate to good yields.Additionally,under modified conditions wherein Hantzsch ester 9 is replaced by an excess of triethylamine, vinyl and alkynyl sulfones can be employed to afford products similar to those reported by Gryko [43] ,b ut without ap hotocatalyst. Additionally,replacing the sulfone reagents by thiol or disulfane enables efficient hydrogen atom transfer (HAT) or thioetherification reactions,respectively.…”

“…Under photoredox catalytic conditions, N-alkyl pyridinium salts have been utilized for the construction of C(sp 3 )ÀC(sp) and C(sp 3 )À C(sp 2 )b onds from alkynyl and vinyl sulfone substrates, respectively. [43] Under basic conditions,t he transiently generated radical resulting from the addition of the alkyl radical to the olefin undergoes oxidation by the reduced photocatalyst and elimination to afford Heck-type products. [44] Notably,H eck-type deaminative alkylation of N-alkyl pyridinium salts can also be mediated efficiently by triphenylphosphine and sodium iodide under irradiation with visible light.…”

“…However,bychoosing N-functional groups that strongly disfavor the formation of the corresponding radical, heterolysis resulting in pyridyl radical cations may become feasible.T his hypothesis was initially corroborated when the formation of apyridyl radical cation by heterolysis of the pyridine-N À Obond was observed as am inor competing pathway in Tognist rifluoromethoxylation (see Section 2.3). [88] Independently and concurrently,Ritter and co-workers as well as acollaboration of the Carreira and Togni groups have reported the selective light-mediated generation of ap yridyl radical cation for the direct C(sp 2 ) À Hamination of arenes and heteroarenes (43). [97,98] Togni, Carreira, and co-workers identified as imple N-trifloxypyridinium salt 58 as well as the commonly available N-fluoropyridinium salt as suitable precursors to generate pyridyl radical cations selectively over the high energy radicals which would result from the commonly observed homolysis pathway,n amely trifloxy or fluorine radicals,r espectively.T he best yields were obtained with the N-trifloxypyridinium 58,which was shown to provide awide range of pyridinylated products 59 (Scheme 26).…”

Pyridiniumsalze als redoxaktive Reagenzien zur Übertragung funktioneller Gruppen

“…Unter photoredoxkatalytischen Bedingungen wurden N ‐Alkylpyridiniumsalze für den Aufbau von C(sp 3 )‐C(sp)‐ und C(sp 3 )‐C(sp 2 )‐Bindungen aus Alkinyl‐ bzw. Vinylsulfonsubstraten genutzt . Unter basischen Bedingungen wird das vorübergehend erzeugte Radikal, das bei der Addition des Alkylradikals an das Olefin entsteht, durch den reduzierten Photokatalysator oxidiert und eliminiert darauffolgend unter Bildung Heck‐artiger Produkte .…”

Visible‐Light‐Promoted C(sp3)−H Alkylation by Intermolecular Charge Transfer: Preparation of Unnatural α‐Amino Acids and Late‐Stage Modification of Peptides

“…However, the primary alkyl substrates, including Katritzky salts derived from n-butylamine (2 k), benzylamine (2 l-2 n), and glycine (2 o) failed to give the desired coupling products (see the Supporting Information). [16] Furthermore, the glycine derivatives bearing different N-aryl groups and glycine amide were well tolerated (3 ba-ea, 80-88 %).…”