Photoredox‐Catalysed Decarboxylative Alkylation of N‐Heteroarenes with N‐(Acyloxy)phthalimides

Abstract

An iridium photoredox catalyst in combination with either a stoichiometric amount of Brønsted acid or a catalytic amount of Lewis acid is capable of catalyzing regioselective alkylation of N-heteroarenes with N-(acyloxy)phthalimides at room temperature under irradiation. A broad range of N-heteroarenes can be alkylated using a variety of secondary, tertiary, and quaternary carboxylates. Mechanistic studies suggest that an Ir /Ir redox catalytic cycle is responsible for the observed reactivity.

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…[90] As ingle-electron transfer between the excited Ir(ppy) 2 (dtbbpy)PF 6 and the pyridinium salt induces reduction and fragmentation of the latter to generate an alkyl radical which then adds on to the heteroarene.I ti sn oteworthy that the pyridinium salts-or Katritzky salts-are easily obtained in one step from the corresponding free amines;t his reaction could, therefore,b es een as at wo-step process for the direct alkylation of heteroarenes from free amines,e ven if such reagents can hardly compete with more classical ones that are able to perform the exact same transformation. Additional processes based on the use of N-tosylhydrazones [92] together with copper catalysis and N-(acyloxy)phthalimides [93] under photoredox conditions were reported for the direct alkylation of N-iminopyridiniums and unfunctionalized heteroarenes. Under oxidative conditions,1 ,4-dihydropyridines undergo homolytic cleavage to generate alkyl radicals that add to the heteroarenes under mild conditions [Scheme 27, Eq.…”

“…Other reagents have indeed been exploited for the selective alkylation of CÀHb onds in electron-deficient heteroarenes:t hey include alcohols, [70][71][72][73] carboxylic acids, [74][75][76][77][78][79][80][81][82][83] peroxides, [84,85] aldehydes, [86][87][88] acyl chlorides, [89] as well as some less common reagents such as pyridinium salts, [90] dihydropyridines, [91] N-tosylhydrazones, [92] N-(acyloxy)phthalimides, [93,94] a-diazocarbonyl derivatives, [95] a-carbonyl alkylsulfones, [96] carboxylic xanthates, [97,98] cycloalkanols, [99,100] and Wittig reagents. [101] Theu se of alcohols as remarkably attractive alkylating agents was elegantly exploited by MacMillan in 2015 for the direct alkylation of pyridine derivatives by using as trategy that combines photoredox catalysis and hydrogen atom transfer catalysis.…”

“…[91] Thet ransformation was amenable to the late-stage functionalization of some pharmaceutical agents and is believed to proceed through ar adical-chain mechanism. Additional processes based on the use of N-tosylhydrazones [92] together with copper catalysis and N-(acyloxy)phthalimides [93] under photoredox conditions were reported for the direct alkylation of N-iminopyridiniums and unfunctionalized heteroarenes. N-(Acyloxy)phthalimides have also been elegantly utilized in combination with an iridium photoredox catalyst and an enantiopure chiral Brønsted acid catalyst for the introduction of amino acid chains onto various quinolines and pyridines, thereby affording the corresponding enantioenriched aheterocyclic amines in good to excellent yields and enantioselectivities.…”

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

“…The transformation was amenable to the late‐stage functionalization of some pharmaceutical agents and is believed to proceed through a radical‐chain mechanism. Additional processes based on the use of N ‐tosylhydrazones together with copper catalysis and N ‐(acyloxy)phthalimides under photoredox conditions were reported for the direct alkylation of N ‐iminopyridiniums and unfunctionalized heteroarenes. N ‐(Acyloxy)phthalimides have also been elegantly utilized in combination with an iridium photoredox catalyst and an enantiopure chiral Brønsted acid catalyst for the introduction of amino acid chains onto various quinolines and pyridines, thereby affording the corresponding enantioenriched α‐heterocyclic amines in good to excellent yields and enantioselectivities .…”

Neue Entwicklungen auf dem Gebiet der Minisci‐Reaktion

“…N-Acyloxypthalimide sind sowohl als Ersatz fürC arbonsäuren als auch als Oxidationsmittel nutzbar, sind dementsprechend also "redoxaktiv" und werden oft als "redoxaktive Ester" (RAEs) bezeichnet. [58,59] In der ersten Arbeit wurde mittels Photoredoxkatalyse die Aminoalkylierung von Heteroarenen mit RAEs aus N-geschützten Aminosäuren erreicht. [55][56][57] Der Einsatz von N-Acyloxyphthalimiden in Minisci-Reaktionen wurde 2017 erstmals in zwei Arbeiten von Shang, Fu und Mitarbeitern beschrieben (Schema 13).…”