Asymmetric dearomatization catalysed by chiral Bronsted acids via activation of ynamides

Chiral Bronsted acid-catalysed asymmetric synthesis has received tremendous interest over the past decades, and numerous efficient synthetic methods have been developed based on this approach. However, the use of chiral Bronsted acids in these reactions is mostly limited to the activation of imine and carbonyl moieties, and the direct activation of carbon-carbon triple bonds has so far not been invoked. Here we show that chiral Bronsted acids enable the catalytic asymmetric dearomatization reactions of naphthol-, phenol- and pyrrole-ynamides by the direct activation of alkynes. This method leads to the practical and atom-economic construction of various valuable spirocyclic enones and 2H-pyrroles that bear a chiral quaternary carbon stereocentre in generally good-to-excellent yields with excellent chemo-, regio- and enantioselectivities. The activation mode of chiral Bronsted acid catalysis revealed in this study is expected to be of broad utility in catalytic asymmetric reactions that involve ynamides and the related heteroatom-substituted alkynes.

Automated summary

The use of chiral Bronsted acids in catalytic asymmetric synthesis enables the direct activation of alkynes, leading to the construction of valuable spirocyclic enones and 2H-pyrroles with high yields and excellent enantioselectivity. This activation mode is expected to be widely applicable in catalytic asymmetric reactions involving ynamides and related heteroatom-substituted alkynes.