Pd(II)-Catalyzed Tandem Cycloannulative-Alkenylation of o-Alkynyl-Phenols/Anilines with (E)-β-Iodovinyl Sulfones: A Direct Strategy To Construct 3-(Vinyl sulfonyl)benzoheterole Derivatives

Abstract

Benzoheteroles and vinyl sulfones are the most promising pharmaceutical relevance motifs, yet the hybrid analogues of these scaffolds still need to be explored. We report herein a general and highly efficient Pd­(OAc)2-catalyzed intramolecular cyclization and vinylation of o-alkynylphenols/o-alkynylanilines with (E)-β-iodovinyl sulfones under mild reaction conditions. A direct C­(sp2)–C­(sp2) cross-coupling is enabled for the diversity-oriented synthesis of vinyl sulfone-tethered benzofurans and indoles in good to high yields with excellent stereoselectivity. Notably, this tandem process was consistent at the gram scale, and in situ, generation of 2-(phenylethynyl)­phenol has also been utilized in a scalable synthesis. Late-stage synthetic transformations were also further explored, including isomerization and desulfonylative-sulfenylation. Moreover, several control experiments were accomplished, and we proposed a plausible mechanism based on existing experimental results.

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

“…Subsequently, a general and highly efficient Pd(OAc) 2 -catalyzed intramolecular cyclization and vinylation of o -alkynylphenols 36 / o -alkynylanilines 39 with ( E )-β-iodovinyl sulfones 3 under mild conditions was reported (Scheme 43). 67 A direct C(sp 2 )–C(sp 2 ) cross-coupling allows for the diversity-oriented synthesis of vinyl sulfone-tethered benzofurans 38 in good to high yields with excellent stereoselectivity using a wide range of o -alkynylphenols and ( E )-β-iodovinyl sulfones. Furthermore, N -tosyl/ N -mesyl-derived o -alkynylanilines 39 and ( E )-β-iodovinyl sulfone were quickly assembled at room temperature to access the expected 3-(vinyl sulfonyl)indoles 40 in decent yields.…”