Unexpected Cascade Reactions of Ortho‐Hydroxyenaminones and β,γ‐Unsaturated α‐Ketoesters to Access Hydrogenated Benzoxazolepolycycles and Pyrrole−Phenol Atropisomers

Abstract

An unexpected BF 3 · OEt 2 -catalyzed Michael addition/cyclization/dehydration sequence of ortho-hydroxyenaminones with aromatic or aliphatic aldehyde-derived β,γ-unsaturated α-ketoesters has been achieved to afford a wide range of fused hydrogenated benzoxazole polycycles in 67-95% yields in a highly diastereoselective manner. When isatin-derived β,γ-unsaturated α-ketoesters were employed as substrates, completely different reactivities were observed, delivering an array of new atropisomers with an oxindole-substituted NÀ C axially chiral pyrroleÀ phenol backbone in up to 97% yield. Moreover, DFT calculations were conducted to account for the possible reaction pathway and the stereochemistry.

Recent Advancements in Pyrrole Synthesis

“…Various motifs of dicarbonyl compounds have been extensively utilized toward pyrrole synthesis. [83][84][85][86][87][88][89][90][91][92][93] As discussed in this section, this class of starting materials have enabled the development of a broad array of new synthetic reactions.…”