Visible‐Light‐Induced Radical Tandem Aryldifluoroacetylation of Cinnamamides: Access to Difluoroacetylated Quinolone‐2‐ones And 1‐Azaspiro[4.5]decanes

Abstract

Av isible light-mediated difluoroacetylation of cinnamamides with ethylb romodifluoroacetate as aC F 2 radical precursori sd escribed. Ther eaction incorporates tandem cyclization or cyclization/dearomatizationp rocesses.T he latter process occurs when there is a p-RO substituento nt he aniline.T hisp rotocola ffords straightforward new routes to separately synthesize quinoline-2-ones and spiro[4.5]decanes in moderate to good yields.

Visible‐light‐catalyzed Tandem Difluoroacetylation–Intramolecular Cyclization of 1,3‐Diarylpropynones: Access to Difluoroacetylated Indenones

“…The mechanism proposed on the basis of control experiments and related literature reports [7][8][9][10][11][12][13][14][15] is illustrated in Scheme 4. Initially, the photocatalyst [fac-Ir III (ppy) 3 ]e xcited by Scheme1.Schematicrepresentation of the present work versus earlier works.…”

“…[3] Severald ifluoromethyl substituted functional groups,i np articular a-difluoromethylphosphonates, a-difluoromethylcarboxylates and a-difluoromethyl amino acid derivatives, are often present in potential therapeutic molecules. [6] Consequently,t he visible-light-photocatalyzedg eneration and addition of ad ifluoromethyl radical to unsaturated systems followed by intramolecular cyclization has emerged as an attractive method for the synthesis of difluoromethylated heterocycles such as pyridine, [7] isoquinolinediones, [8] oxindole, [8,9] lactones, [10] phenanthridine, [11] benzo[j]phenanthridine, [12] quinolone-2-ones, [13] and 1-azaspiro[4.5]decanes. [6] Consequently,t he visible-light-photocatalyzedg eneration and addition of ad ifluoromethyl radical to unsaturated systems followed by intramolecular cyclization has emerged as an attractive method for the synthesis of difluoromethylated heterocycles such as pyridine, [7] isoquinolinediones, [8] oxindole, [8,9] lactones, [10] phenanthridine, [11] benzo[j]phenanthridine, [12] quinolone-2-ones, [13] and 1-azaspiro[4.5]decanes.…”

“…[4] Althoughs everal nucleophilic, electrophilic,a nd free-radical difluoromethylation strategies have been extensively explored, [5] the difluoromethylation of organic compounds under visiblelight-photocatalyzedc onditions gained popularity only recently. [13,14] Recently,F u and co-workers reportedt he synthesis of difluoroacetylated coumarins via visible-light-mediated radicald ifluoroacetylation of alkynoates. [13,14] Recently,F u and co-workers reportedt he synthesis of difluoroacetylated coumarins via visible-light-mediated radicald ifluoroacetylation of alkynoates.…”

Visible‐Light‐Induced Dearomatizations

“…In this transformation, Togni's reagent was used as a trifluoromethyl source to initiate the process, in the presence of [Ir(ppy) 3 ] as a catalyst under blue LED visible‐light conditions. At the same time, Zhu and co‐workers reported a similar protocol using ethyl bromodifluoroacetate as a CF 2 radical precursor under visible‐light irradiation, providing access to difluoroacetylated azaspiro[4.5]decane . In both scenarios, moderate to good yield of the desired azaspiro compounds were obtained, with or without the protection of phenol moiety.…”

Tandem Radical Cyclization for the Construction of Difluoro‐Containing Oxindoles and Quinoline‐2,4‐diones

“…To our surprise, when we switched the substituent ‐H on R 3 to the ‐Ph group, the quinoline‐2‐one derivatives were obtained in good yields ( 3 ab and 3 ac ). It was noted that when R 1 substituted by ‐OMe group, the product is different from the previous reported structure 1‐azaspiro[4.5]decane …”