Visible-light-induced cascade radical ring-closure and pyridylation for the synthesis of tetrahydrofurans

Abstract

A novel visible-light-enabled alkoxy radical ring-closure and pyridylation from N-alkenyloxypyridinium salts was achieved under metal-free mild conditions, offering a powerful synthetic tool for assembling various pyridine-tethered tetrahydrofurans.

Pyridinium Salts as Redox‐Active Functional Group Transfer Reagents

“…[84] After generation of the transient alkoxy radical mediated by ap hotoexcited quinolinone catalyst 33, radical translocation of the alkoxy radical 34 by 1,5-HAT generates an ucleophilic alkyl radical intermediate 35.A lkyl radical 35 undergoes addition to pyridinium 32 to achieve remote C(sp 3 ) À Hh eteroarylation while generating an ew oxygen-centered radical 34.Notably,ifthe substrate contains an olefinic bond in the 5-position, radical ring-closure and subsequent pyridination is observed. [85] Scheme 16. Oxidation of alcohols with N-methoxypyridinium salts.…”

Visible‐Light‐Induced ortho‐Selective Migration on Pyridyl Ring: Trifluoromethylative Pyridylation of Unactivated Alkenes

“…Despite this inspiration, the crucial challenge in this proposed approach may lie in the competitive fragmentation of the N‐alkoxypyridinium salts by single‐electron transfer (SET), leading to the formation of alkoxy radicals and pyridines . Therefore, a successful photocatalytic system using this approach requires the selective generation of radicals to promote the group migration to the ortho ‐position of the pyridyl ring, while minimizing the competing process of N−O bond cleavage to prevent undesired reactions, exemplified by alkoxy radical cyclization . Herein, we report the successful realization of a trifluoromethylative pyridylation of alkenes through an ortho ‐selective migration strategy.…”

“…In line with our hypothesis, the feasibility of the proposed ortho ‐selective migration was investigated using the N‐alkoxypyridinium salt 1 a (Table ) as a model substrate under blue LED irradiation. In the absence of the CF 3 radical source, illuminating a photocatalyst such as the 3‐phosphonated quinolinone Q 1 or Eosin Y (EY) enables the formation of the alkoxy radical that triggers a competing intramolecular alkoxy radical cyclization with an alkene and subsequent pyridylation, leading to the formation of pyridine‐tethered tetrahydrofuran (see the Scheme S7 in the Supporting Information for details) . We next examined the use of the Langlois reagent 2 as a CF 3 radical source by a reductive quenching photocatalytic cycle .…”

“…[13] Therefore,asuccessful photocatalytic system using this approach requires the selective generation of radicals to promote the group migration to the ortho-position of the pyridyl ring, while minimizing the competing process of N À O bond cleavage to prevent undesired reactions,exemplified by alkoxy radical cyclization. [14] Herein, we report the successful realization of at rifluoromethylative pyridylation of alkenes through an ortho-selective migration strategy.N otably,t his strategy enables not only secondary,b ut also tertiary alkyl radicals to react with the C2-position of pyridinium salts, overriding the commonly observed preference for the C4addition. Moreover,t he utility of the current method was further expanded by successfully applying it to the reaction with P-centered radicals.…”

“…In the absence of the CF 3 radical source,i lluminating ap hotocatalyst such as the 3-phosphonated quinolinone Q 1 [15] or Eosin Y( EY) enables the formation of the alkoxy radical that triggers ac ompeting intramolecular alkoxy radical cyclization with an alkene and subsequent pyridylation, leading to the formation of pyridinetethered tetrahydrofuran (see the Scheme S7 in the Supporting Information for details). [14] We next examined the use of the Langlois reagent 2 as aCF 3 radical source by areductive quenching photocatalytic cycle. [16] To our delight, the desired product 3a was formed through trifluoromethylative ortho-selective pyridyl migration when Q 1 was used as ap hotocatalyst (entry 1, 33 %y ield), highlighting that the proposed overall process can be achieved effectively.T he results revealed that the dissociation of the N À Ob ond in 1a could be minimized in the presence of NaSO 2 CF 3 (see the Scheme S7 for details).…”