Silver-mediated radical 5-exo-dig cyclization of 2-alkynylbenzonitriles: synthesis of phosphinylated 1-indenones

Abstract

A new silver-mediated 5-exo-dig cyclization of 2-alkynylbenzonitriles with disubstituted phosphine oxide and HO has been developed. The reaction enables multiple bond-forming events including C-P, C-C and C-O bonds under atmospheric conditions, leading to the concise and direct formation of 28 examples of phosphorus-containing 1-indenones with generally good yields.

DBU‐Mediated Intermolecular 5‐exo‐dig Cyclization of PropargylAlcohols and Carbon Disulfide to [1,3]‐Oxathiole‐2‐thiones

“…Here, either alkyne or alkynol is an alternate and versatile reagent for o‐halophenol to synthesis cyclic compounds due to its dual nature, both electrophilic and nucleophilic. A number of reports are published on the cyclization of alkyne via 5‐ exo ‐dig: for example silver‐mediated radical cyclization of 2‐alkynylbenzonitriles produced phosphinylated 1‐indenones and enediynes, a similar method also produced benzofulvenes . Likewise, Pd‐catalyzed 5‐ exo‐dig cyclization of alkyl amine with acid chloride offered excellent yield of switchable oxazolines and oxazoles.…”

Sulfinate‐Salt‐Mediated Radical Relay Cyclization of Cyclic Ethers with 2‐Alkynylbenzonitriles toward 3‐Alkylated 1‐Indenones

“…The use of bases, such as K 2 CO 3 and Et 3 N, was anticipatedt oi mprove this transformation, but very disappointed results were given (entries [3][4]. The use of other silver salts, such as silver acetate (AgNO 3 )a nd silver trifluoromethanesulfonate (AgOTf) completely suppressed the reaction process (entries13-14).T he following screening of oxidants revealed that di-tert-butyl peroxide (DTBP) and tert-butyl peroxybenzoate (TBPB) were found to have ad etrimental impact on the reaction yields (entries [15][16]. To our delight, the reactioni nt he presence of 2.0 equivalents of sodium methanesulfinate (CH 3 SO 2 Na) provided the expected 1-indenone product 3a,a lbeit with al ow 25 %y ield (entry 5), indicating that sulfinate salts could serve as ar adicalm ediatort oa chieve the radicalr elay process.…”

“…Without CF 3 CO 2 Ag or lowering its dosage, the unsatisfactoryo utcomes were observed (entries 10-12). The use of other silver salts, such as silver acetate (AgNO 3 )a nd silver trifluoromethanesulfonate (AgOTf) completely suppressed the reaction process (entries13-14).T he following screening of oxidants revealed that di-tert-butyl peroxide (DTBP) and tert-butyl peroxybenzoate (TBPB) were found to have ad etrimental impact on the reaction yields (entries [15][16]. The reaction gave ar elativelyl ower conversion when the reactiont emperature was adjusted to either 90 or 50 8C( entries 17-18).…”

“…To the best of our knowledges, there is no precedent report on the constructiono f3 -alkylated 1-indenones through the radicalr elayc yclization of 2-alkynylbenzonitriles with cyclic ethers. [16]…”

Recent Advances in Radical‐Enabled Bicyclization and Annulation/1,n‐Bifunctionalization Reactions

“…Performing the reaction in MeCN at 80 8Cp roceeded readily with AgNO 3 as the oxidant, thereby allowinga ccess to 28 examples of phosphorus-containing 1-indenones 181 in 40-76 %y ields (Scheme 45 a). [73] This transformationi nvolved the addition of aP -centered radical, a 5-exodig cyclization, and hydrolysis (Scheme 45 b), thereby resulting in successive multiple bond-forming events, including the formationo fC ÀP, CÀC, and CÀOb onds in ao ne-pot manner. As a continuation of this work, the same group developed as ulfinate-salt-mediated radical relay strategy by using 2-alkynylbenzonitriles as radical acceptors, thereby affording aw ide range of 3-alkylated 1-indenones 183 in typically good yields.…”