Direct Reductive Quinolyl β-C–H Alkylation by Multispherical Cavity Carbon-Supported Cobalt Oxide Nanocatalysts

Abstract

Until now, the selective (hetero)­aryl C–H alkylation without the assistance of directing groups or preinstallation of functionalities still remains a highly challenging goal. Herein, by developing acid-resistant multispherical cavity carbon-supported cobalt oxide nanocatalysts (CoO x /MSCC) and a hydrogen transfer-mediated activation mode for nonactivated N-heteroaromatics, we present a direct reductive quinolyl and isoquinolyl β-C–H alkylation with various aldehydes as the alkylating agents. The catalytic transformation features broad substrate scope, good functional tolerance, use of Earth-abundant and reusable cobalt catalysts, and no need for prefunctionalizations, demonstrating that the developed nanocatalysts enable one to directly functionalize inert N-heteroaryl systems that are difficult to realize by organometallic complexes.

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

“…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.…”

“…[86] Whereas secondary and tertiary aldehydes proved efficient, the use of primary ones led to substantial amounts of acylation products.D i-tert-butylperoxide was also shown to efficiently generate radicals from primary,s econdary,a nd tertiary aldehydes at elevated temperature for the alkylation of several common nitrogen-containing heterocycles,a sw ell as of some azoles. [88] Finally,acyl chlorides were shown to be competent alkylating agents under iridium photoredox conditions via the generation of redox active complexes upon condensation with pyridine N-oxides. [88] Finally,acyl chlorides were shown to be competent alkylating agents under iridium photoredox conditions via the generation of redox active complexes upon condensation with pyridine N-oxides.…”

“…[87] Moreover,multispherical-cavity carbonsupported cobalt oxide nanoparticles have been used for the direct C3-alkylation (mostly benzylation) of quinolines by using aldehydes in the presence of hydrogen peroxide. [88] Finally,acyl chlorides were shown to be competent alkylating agents under iridium photoredox conditions via the generation of redox active complexes upon condensation with pyridine N-oxides. [89] After decarboxylation and C2-alkylation, the corresponding C2-alkylated pyridines (and related azines) were obtained in low to good yields.…”

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

“…Di‐ tert ‐butylperoxide was also shown to efficiently generate radicals from primary, secondary, and tertiary aldehydes at elevated temperature for the alkylation of several common nitrogen‐containing heterocycles, as well as of some azoles . Moreover, multispherical‐cavity carbon‐supported cobalt oxide nanoparticles have been used for the direct C3‐alkylation (mostly benzylation) of quinolines by using aldehydes in the presence of hydrogen peroxide . Finally, acyl chlorides were shown to be competent alkylating agents under iridium photoredox conditions via the generation of redox active complexes upon condensation with pyridine N ‐oxides .…”

Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

“…Auch andere Reagenzien wurden fürd ie selektive Alkylierung von C-H-Bindungen in elektronenarmen Heteroarenen genutzt:H ierzu zählen Alkohole, [70][71][72][73] Carbonsäuren, [74][75][76][77][78][79][80][81][82][83] Peroxide, [84,85] Aldehyde, [86][87][88] Acylchloride [89] sowie…”