Olefination of Aromatic Carbonyls via Site-Specific Activation of Cycloalkanone Ketals

Skeletal editing is an important strategy in organic synthesis as it modifies the carbon backbone to tailor molecular structures with precision, enabling access to compounds with specific desired properties. Skeletal editing empowers chemists to transform synthetic approaches of target compounds across diverse applications from drug discovery to materials science. Herein, we introduce a new skeletal editing method to convert readily available aromatic carbonyl compounds into valuable unsaturated carboxylic acids with extended carbon chains. Our reaction setup enables a cascade reaction of enolization-[2+2]cycloaddition-[2+2]cycloreversion between aromatic carbonyl compounds and ketals of cyclic ketones to generate unsaturated carboxylic acids as ring-opening products. Through a simple design, our substrates are specifically activated to react at predetermined positions to enhance selectivity and efficiency. This practical method offers convenient access to versatile organic building blocks as well as provides fresh insights into manipulating traditional reaction pathways for new synthetic applications.