Atroposelective Construction of Axially Chiral Alkene-Indole Scaffolds via Catalytic Enantioselective Addition Reaction of 3-Alkynyl-2-indolylmethanols†

Main observation and conclusion Atroposelective construction of axially chiral alkene-heteroaryl scaffolds is highly desired but challenging. In this work, we established an atroposelective construction of axially chiral alkene-indole scaffolds via the strategy of catalytic enantioselective addition reaction of 3-alkynyl-2-indolylmethanols with bulky nucleophiles. In this strategy, alpha-amido sulfones were used as competent nucleophiles and chiral phosphoric acid (CPA) acted as suitable chiral catalyst for this addition reaction. By this strategy, a new class of axially chiral acyclic alkene-indoles was synthesized in overall high yields (up to 86%), excellent (E/Z)-selectivity (all > 95 : 5) and good enantioselectivities (up to 92 : 8 er). This reaction represents the first catalytic enantioselective construction of axially chiral alkene-indole frameworks, which will add a new member to the family of atropoisomeric heterocycles, especially the family of axially chiral indole compounds.

Automated summary

This work presents a catalytic enantioselective construction of axially chiral alkene-indole frameworks using alpha-amido sulfones as nucleophiles and chiral phosphoric acid as catalyst. The strategy resulted in high yields, excellent (E/Z)-selectivity, and good enantioselectivities, representing the first of its kind in the construction of axially chiral alkene-indole scaffolds.