Diastereoselective Cascade Annulation of Distal Formyl Enones and Sulfur Ylides toward Cyclopropane-Fused Cycloalkanes

A metal-free cascade annulation that harnesses the ambiphilic reactivity of distal formyl enones and sulfur ylides is developed to access high-value cyclopropane-fused cycloalkanes. Using readily accessible 6-formyl enones, the method delivers a diverse array of functionally rich cyclopropane-fused cyclohexanes bearing four contiguous stereocenters in high yields as single diastereomers. The protocol is also amenable to 5-formyl enones, affording cyclopropane-fused cyclopentane analogues, while 7-formyl enones, with a longer carbon spacer, undergo a mechanistically distinct cascade to afford cyclopentane-tethered cyclopropanes with excellent yields and diastereoselectivity. The protocol is operationally simple and scalable and displays a wide substrate generality along with scaffold diversity.