Regioselective Alkyne–Aldehyde Coupling under Metal‐Free and Reductant‐Free Conditions

Herein, we described a novel strategy for regioselective alkyne–aldehyde coupling without the use of catalysts and exogenous reductants. The coupling involved a self‐assembly triple cascade reaction of acyl‐stabilized sulfur ylides with two different aldehydes. Critical to the success of the alkyne–aldehyde coupling is that acyl‐stabilized sulfur ylides react with substituted propiolaldehydes preferentially to form a key multisubstituted 2,3‐dihydrofurylsulfonium salt intermediate bearing a thionium cation at the homopropargylic position, which can be subsequently captured by arylaldehydes as electrophiles via an allenic anion. This multicomponent domino reaction provides easy access to structurally diverse and densely functionalized furan‐substituted allylic alcohols from three simple starting materials under mild, operationally simple conditions, with exclusive chemo‐ and regioselectivity, excellent E / Z selectivity, a wide substrate scope, and high functional group tolerance. Moreover, the furan‐substituted allylic alcohol products showed greater bioactivity against liver fibrosis than pifenidone, a broad‐spectrum treatment for fibrosis, hence showing potential to be used as lead candidates for anti‐liver fibrosis treatments.