Metal‐Free Hydroxyalkylation‐Initiated Radical Cyclization of 1,6‐Enynes with Alcohols

Abstract

Without employing any metal catalyst or organic solvents, a practical, efficient and environmentally attractive protocol has been established for the hydroxyalkylationinitiated radical cyclization of 1,6-enynes with alcohols under open air conditions. This transformation proceeds through C(sp 3 )À H bond functionalization, oxyalkylation and intramolecular cyclization, providing a novel approach to 2pyrrolidinones in good to excellent yields. 4 5 6 7 8

C-centered radical-initiated cyclization by directed C(sp3)–H oxidative functionalization

“…By employing the C(sp 3 )–H oxidative functionalization strategy, alcohols 114 and ethers 115 were also investigated to construct pyrrole derivatives. Regarding the mechanistic study, KIE experiments ( K H / K D = 3 (ref.…”

Radical Cyclization of 1,n‐Enynes and 1,n‐Dienes for the Synthesis of 2‐Pyrrolidone

“…In 2019, our group discovered that reacting structurally simple alcohols with 1,6‐enynes in the presence of TBHP led to the formation of 2‐pyrrolidones through α ‐C( sp 3 )−H bond functionalization (Scheme 7). [19] Compared to existing methods, this reaction not only utilized metal‐free and mild reaction conditions, but also both the N ‐aryl rings and the alcohol substrates bearing different functional groups were well‐tolerated, leading to the formation of the corresponding N ‐arylpyrrolidinone products in moderate to high yields.…”

“…In light of the previous work with 1, n ‐enynes and alcohols, [19] we considered whether a similar reaction could occur between 1, n ‐dienes and alcohols. After investigating the potential of this reaction, we reported in 2020 a method for the radical cyclization of 1,6‐dienes with alcohols using TBPB as a radical initiator in the absence of a catalyst, which resulted in the synthesis of various 2‐pyrrolidone derivatives featuring various oxygen‐containing functional groups, depending on the degree of oxidation of the alcohol functional group (Scheme 32).…”

Structure-guided insights into non-catalytic (α-hydroxy)alkylation of olefins with alcohols

“…For the successful C–C coupling of olefins with alcohols, external chemical factors are highly required, among which homogeneous metal-based (FeCl 3 , 6 RhCl(PPh 3 ) 3 , 5 Pd(OAc) 2 /PPh 3 , 30 etc. ) or heterogeneous supported (Pt/TiO 2 , Pd/TiO 2 , Ru/TiO 2 , and Au/TiO 2 31 ) catalysts, as well as free-radical initiators ( tert -butyl hydroperoxide, 32 di- tert -butyl peroxide, 33 tert -butyl peroxyacetate, 9 dicumyl peroxide, 9 etc. ) dominate.…”

“…) catalysts, as well as free-radical initiators (tert-butyl hydroperoxide, 32 di-tert-butyl peroxide, 33 tert-butyl peroxyacetate, 9 dicumyl peroxide, 9 etc.) dominate.…”