Deoxygenative Arylation of Carboxylic Acids by Aryl Migration

Abstract

An unprecedented deoxygenative arylationo f aromatic carboxylic acids has been achieved, allowing the construction of an enhanced libraryo fu nsymmetrical diaryl ketones.T he synergistic photoredox catalysis and phosphoranyl radical chemistrya llows for precise cleavage of as tronger CÀOb ond and formation of aw eaker CÀC bond by 1,5-arylm igrationu nder mild reaction conditions. This new protocol is independent of substrate redox-potential,e lectronic, and substituent effects. It affords ag eneral and promising access to 60 examples of synthetically versatile o-amino and o-hydroxyd iaryl ketones under redox-neutral conditions. Furthermore,i ta lso brings one conciser oute to the total synthesis of quinolone alkaloid, (AE)-yaequinolone A2, and av iridicatin derivative in satisfying yields.

Upgrading ketone synthesis direct from carboxylic acids and organohalides

“…5) and found that many commercially available aromatic bromides can be used to deliver the desired ketones (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46) in good yields. The excellent functional group tolerance of -COOR (28,33,44,45), -CN (29, 34), terminal unsaturated chemical bonds (43,44), and heteroarenes (38)(39)(40)(41)(42)(43)46) support the practicality of the reaction. With this strategy, it is also very easy to construct fluorineand fluoroalkylcontaining diaryl ketones (30-32, 36, 37, 39-42) with acceptable yields.…”

“…This could simplify and upgrade ketone synthesis from carboxylic acids and organic halides 13 . Very recently, our group and Doyle et al reported an elegant photoredoxpromoted mild deoxygenation of carboxylic acids generating acyl radicals [31][32][33][34][35] . Since photoredox and nickel-catalyzed C-O bond formation between carboxylic acids and aromatic bromides has been reported 36 to achieve the desired crosselectrophile coupling, acyl radical oxidative addition by a metallaphotoredox pathway [37][38][39][40][41] is essential to suppress the C-O bond formation (Fig.…”

“…Alternatively, a judicious strategy reported by Gong et al is conversion of carboxylic acid into anhydrides in situ to suppress the C-O coupling 22,23 . However, the use of free carboxylic acids as acyl radical precursors is a challenge in the oxidative addition step as a result of the strong bond dissociation energy of the C-O bond (106 kcal mol −1 ) 33 .…”

Phosphorus Compounds as Precursors and Catalysts for Radical C−C Bond‐Forming Reactions

“…Following from their previous work on intramolecular hydroacylation from carboxylic acids, the Zhu group reported an intramolecular deoxygenative arylation to form diarylketones 79 (Scheme 18). [43] This reaction follows a similar initial pathway, with the formation of the triphenylphosphine radical cation and subsequent deoxygenation to form the acyl radical 80 . This radical then undergoes an ipso 1,6‐addition to the aryl sulfonamide to form intermediate 81 , followed by extrusion of SO 2 to give the aminyl radical 82 .…”

Spotlight on Photoinduced Aryl Migration Reactions

“…In this context, Zhu and co‐workers described a photoredox‐mediated deoxygenative aryl migration of aromatic carboxylic acids to allow the efficient synthesis of unsymmetrical diaryl ketone scaffolds (Scheme 16). [19] …”