Remote methylene C(sp3)-H functionalization enabled by organophosphine-catalyzed alkyne isomerization

A remote delta methylene C(sp(3))-H functionalization catalyzed by an organophosphine through an alkyne isomerization/conjugate addition cascade was discovered. No classical electron-withdrawing group is required to pre-activate the aryl alkyne, which will undergo isomerization to its corresponding diene under only 10 mol% of PMe2Ph with a catalytic proton shuttle. The phosphoryl ylide was postulated as a key intermediate and different electrophiles were used to trap the vinylogous ylide that resulted in a large group of delta C(sp(3))-H functionalized products (>60 examples, yields up to 99%) with good diastereoselectivity. Mechanistic studies were carried out and a catalytic cycle was proposed based on deuterium-labeling experiments. The conjugated polyene products were investigated for their fluorescence properties.

Automated summary

A novel remote delta methylene C(sp(3))-H functionalization was discovered, catalyzed by an organophosphine through alkyne isomerization/conjugate addition cascade without the need for a classical electron-withdrawing group. The process, under only 10 mol% of PMe2Ph with a catalytic proton shuttle, successfully produced a large group of functionalized products with good diastereoselectivity. Mechanistic studies and fluorescence properties of the conjugated polyene products were investigated in detail.