Unified Radical Sulfonylative-Annulation of 1,6-Enynols with Sodium Sulfinates: A Modular Synthesis of 2,3-Disubstituted Benzoheteroles

Abstract

Benzoheteroles are valuable scaffolds in medicinal chemistry, but the direct synthesis of 3-vinyl benzoheterole analogues remains unexplored. A rationally designed new class of 1,6-enyne-containing propargylic alcohols has been prepared for the modular synthesis of 3-alkenyl benzoheteroles. Ag-catalyzed cascade radical sulfonylative-cycloannulation of 1,6-enynols with sodium sulfinates is realized to access a wide variety of 2,3-disubstituted benzoheteroles in good to high yields. Moreover, a three-component coupling of 1,6-enynols, aryldiazonium salts, and Na 2 S 2 O 5 (as an SO 2 surrogate) has been achieved to deliver benzoheterole derivatives in moderate to good yields. Of note, a scalable reaction and late-stage synthetic transformations were successfully demonstrated. A plausible mechanism is also presented based on the existing experimental results and control experiments.

Recent trends in the synthesis and applications of β-iodovinyl sulfones: a decade of progress

“…We recently established a sequential one-pot method for synthesizing chromene-tethered vinyl sulfones 37 using ( E )-β-iodovinyl sulfones 3 and ortho -alkynylphenols 36 (Scheme 42). 66 The oxa-Michael addition–elimination followed by cycloisomerization and sulfonyl migration was achieved in a single synthetic operation under the influence of Mn(OAc) 3 ·2H 2 O. A broad range of vinyl sulfone-tethered chromenes were readily accessed in moderate to high yields with good functional group compatibility.…”

Recent Advances in Radical Transformations of Propargylic Alcohols

“…In 2023, Krishna's group [14] reported AgNO 3 ‐catalyzed cascade radical sulfonylation/cyclization of 1,6‐enynols 17 with sodium sulfinates in the presence of K 2 S 2 O 8 , affording various 2,3‐disubstituted benzofurans 18 in moderate to good yields (Scheme 7). Both diaryl‐ and dialkyl‐substituted propargylic alcohols in 1,6‐enynols 17 can also successfully participate in this cascade cyclization to afford the corresponding target products.…”