Combined Photoredox and Carbene Catalysis for the Synthesis of γ‐Aryloxy Ketones

Abstract

N‐heterocyclic carbenes (NHCs) have emerged as catalysts for the construction of C−C bonds in the synthesis of substituted ketones under single‐electron processes. Despite these recent reports, there still remains a need to increase the utility and practicality of these reactions by exploring new radical coupling partners. Herein, we report the synthesis of γ‐aryloxyketones via combined NHC/photoredox catalysis. In this reaction, an α‐aryloxymethyl radical is generated via oxidation of an aryloxymethyl potassium trifluoroborate salt, which is then added into styrene derivatives to provide a stabilized benzylic radical. Subsequent radical‐radical coupling reaction with an azolium radical affords the γ‐aryloxy ketone products.

Aroyl Fluorides as Bifunctional Reagents for Dearomatizing Fluoroaroylation of Benzofurans

“…Although another reaction pathway involving C–F bond formation prior to C–C coupling might be possible and cannot be totally ruled out, the fact that moderate enantioselectivity was observed when chiral NHC catalyst was used in the reaction argues in favor of a preferential occurrence of radical cross-coupling. On basis of these experiments and previous reports, 91 − 96 , 100 a mechanism is proposed in Scheme 5 d. Upon visible light irradiation, benzofuran 1a ( E 1/2 = 1.28 V vs SCE) is oxidized to its radical cation 1a-1 by photoexcited Ir(III)*. On the other hand, the reaction of 2a with the NHC gives the acyl azolium ion 2a-I ( E 1/2 = −1.29 V vs SCE), 91 which is reduced by Ir(II) ( E 1/2 (P/P •– ) = −1.37 V vs SCE) to regenerate Ir(III) with the formation of the persistent ketyl radical 2a-II .…”

“… 85 − 97 Reaction of an aroyl fluoride with an NHC catalyst will lead to an aroyl azolium ion that can be SET reduced by a photocatalyst (PC) to generate a ketyl radical. 91 − 96 Oxidation of benzofuran by the PC will give its radical cation that should cross-couple with the ketyl radical to give an oxocarbenium ion. Trapping by the F-anion and NHC fragmentation should lead to the fluoroaroylation product.…”

Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones

“…Multi-component radical relay reactions provide a powerful tool for the synthesis of complex skeletons from simple and readily accessible starting materials 80 – 82 . While significant progress has been achieved in NHC and photocatalyst co-catalyzed ketone synthesis 57 – 64 , 83 , three-component radical relay coupling that allows various carbon radicals involved is still limited 72 .…”

“…bring undesired operations and pose limitations on substrate scopes. In addition, despite the seminal work achieved in NHC and photocatalyst co-catalyzed ketone synthesis 57 – 64 , three-component radical relay coupling that involves various carbon radicals is still limited 58 , 72 .

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Synthesis of Pincer type carbene and their Ag(I)-NHC complexes, and their Antimicrobial activities

“…Formation reactions for complex compounds involve the breaking of electron-rich olefins [37] by way of transition metals with low oxidation. The presentation of Ag(I)-NHC complexes, the transmetallation pathway [38] and stabilized N-heterocyclic carbine [39] make synthesis of functionalized carbene complexes possible in dissimilar studies.…”