Abstract:Recent developments and future prospects of visible-light photocatalysis in the late-stage functionalization of pharmaceuticals and natural bioactive compounds.
“…It is noteworthy that the labile peroxide subunit in artesunate was tolerated particularly well under mild conditions. This powerful method enables the streamlined synthesis of drug analogs, providing attractive opportunities for the rapid exploration of structure-activity relationships in drug discovery 62 , as well as complementing the existing methods for the synthesis chiral α-aryl ketones 7 − 13 . Fig.…”
Asymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.
“…It is noteworthy that the labile peroxide subunit in artesunate was tolerated particularly well under mild conditions. This powerful method enables the streamlined synthesis of drug analogs, providing attractive opportunities for the rapid exploration of structure-activity relationships in drug discovery 62 , as well as complementing the existing methods for the synthesis chiral α-aryl ketones 7 − 13 . Fig.…”
Asymmetric C(sp3)−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis of α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms a diverse array of feedstock carboxylic acids and simple alkyl benzenes into highly valuable α-aryl ketones with high enantioselectivities. The utility of this method is showcased in the gram-scale synthesis and late-stage modification of medicinally relevant molecules. Mechanistic studies suggest a photocatalytically generated bromine radical can perform benzylic C−H cleavage to activate alkylarenes as nucleophilic coupling partners which can then engage in a nickel-catalyzed asymmetric acyl cross-coupling reaction. This bromine-radical-mediated C−H activation strategy can be also applied to the enantioselective coupling of alkylarenes with chloroformate for the synthesis of chiral α-aryl esters.
“…This mini-review summaries the representative reports on the syntheses of isoquinolones and polycyclic-fused isoquinolones by annulation protocols in one-pot manner, which show atom-and step-economy. The new trend of developing annulation reactions in the synthesis of cyclic compounds has recently been diversified; in addition to transition-metal catalysis, the electrocatalysis [133][134][135][136][137] and photocatalysis [138][139][140][141] with or without combination of metal-catalyzed catalysis have also become the novel and elegant methods in annulation synthesis. The construction of isoquinolone ring under these conditions has also been developed via [4 + 2] annulation of benzamides with terminal/internal alkynes [142][143][144][145][146][147].…”
Isoquinolones (isoquinolin-1(2H)-ones) are one of the important nitrogen-heterocyclic compounds having versatile biological and physiological activities, and their synthetic methods have been recently developed greatly. This short review illustrates the significant advances in the construction of isoquinolone ring with atom- and step-economy, focusing on the intermolecular annulation protocols and intramolecular cyclization in the presence of a variety of catalyst systems. The syntheses of isoquinolone-fused rings are also included.
“…Interestingly, regioselectivity for CH 3 oxidation was observed when N-ethyl-N-methylaniline was used as the starting amine component (23). To further explore the potential of the mild developed conditions, late-stage functionalization 19 of complex molecular scaffolds such as indomethacin and gemfibrozil afforded derivatives 24 and 25 in 31 and 58% yield, respectively (Figure 1).…”
A new visible light photocatalytic multicomponent reaction (MCR) involving N-alkyl-N-methylanilines, N-isocyanoiminotriphenyl phosphorane, and carboxylic acids leading to 1,3,4-oxadiazole derivatives is herein reported. The developed mild reaction conditions enable a broad substrate scope and a good functional group tolerance, as further highlighted in the late stage functionalization of amino acids and drugs. Additionally, a 2-step one-pot protocol for the obtention of non-symmetrical diacylhydrazines is also reported as an expeditious and green synthetic approach to such valuable scaffolds.
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