Electrochemical Synthesis of 1-Naphthols by Intermolecular Annulation of Alkynes with 1,3-Dicarbonyl Compounds

Abstract

C-centered radical cyclization under electrochemical conditions is a feasible strategy for constructing cyclic structures. Reported herein is the electrochemical synthesis of highly functionalized 1-naphthols using alkynes and 1,3-dicarbonyl compounds by (4 + 2) annulation of C-centered radical. Electrolysis was conducted with Cp2Fe as redox catalyst, thereby eliminating the use of oxidants and transition-metal catalysts. The synthesized 1-naphthol compounds showed good antitumor activity in vitro, and further studies indicated that compound 3bl induced tumor cell apoptosis.

Electrochemically-mediated C–H functionalization of allenes and 1,3-dicarbonyl compounds to construct tetrasubstituted furans

“…So far, only Ackermann's group has reported two electrochemical C-H activation reactions using allene as substrate via cobalt catalyst 55,56 (Scheme 2a). In our previous work, we synthesized functionalized 1-naphthols using alkynes and 1,3-dicarbonyl compounds under electrochemical conditions, which undergone a C-radical pathway 57 (Scheme 2b). It is known from the reported literature that the activation barrier of the carbon radical addition reactions of alkynes and allenes are similar.…”

Electrochemical Generation and Use in Organic Synthesis of C‐, O‐, and N‐Centered Radicals

“…e) Xu's electrochemical annulation of N‐allyl amides with 1,3‐dicarbonyl compounds [51] . f) Pan's synthesis of 1‐naphtols [52] . *Current density (J) calculated from the RVC electrode reported dimensions and the approximate surface area of the RVC of 100 PPI, 66 cm 2 /cm 3 [53] …”

“…The synthesis of 1‐naphthols ( 86 ) by the intermolecular (4+2) annulation of alkynes with 1,3‐dicarbonylic compounds (Scheme 8f) was promoted by the redox system Fc. Benzoylacetate ester ( 84 ) derivates produce an α‐C centered radical through indirect oxidation mediated by the ferrocene system [52] . The proposed mechanism is a radical cascade reaction that involves the alkyne ( 85 ), obtaining as final compounds naphthol derivatives.…”

Electrifying green synthesis: recent advances in electrochemical annulation reactions

“…61 In the same way, Pan and co-workers proposed a synthesis of 1-naphthols 44 by C-centered radical cyclization of highly functionalized 1,3-dicarbonyl compounds 42 with alkynes 43 by [4 + 2] intermolecular annulation (Scheme 12). 62 The reaction was conducted in an undivided cell in the presence of Cp 2 Fe as a catalyst in a THF : EtOH (1 : 1) mixed solvent at a constant potential of 1.15 V vs. Ag/AgCl with NaOEt (30 mol%) as the base. Both the electron donating and electron withdrawing substituents were evaluated and all groups showed good yields (up to 84%).…”