Palladium-Catalyzed Enantioselective Heteroarenyne Cycloisomerization Reaction

Abstract

The extensively developed ene-type enantioselective cycloisomerization of classical 1,n-enynes provides an efficient approach to chiral cyclic 1,4-dienes. In contrast, the catalytic asymmetric heteroarenyne (heteroarene-alkyne) cycloisomerization involving the dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH-catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne-tethered indole substrates (formal 1,5- and 1,6-enynes). Based on this strategy, a variety of structurally diverse chiral spiro and fused indoline derivatives bearing quaternary stereocenters and exocyclic C=C bonds are afforded in moderate to excellent yields and excellent enantioselectivities (up to 98 % ee). The classical ene-type enantioselective 1,5-enyne cycloisomerization of N-vinylpropiolamides is also developed to afford chiral 2-pyrrolones in good to excellent ee values.

Keywords: asymmetric catalysis; cycloisomerization; dearomatization; heteroarenynes; palladium.