Rh-Catalyzed [8+1] Cycloaddition of Vinyl Biscyclopropanes with CO for the Synthesis of Nine-Membered Carbocycles

Abstract

Transition-metal-catalyzed cycloadditions to access nine-membered carbocycles are challenging, with only three documented examples so far. Here, we report the design of an eight-carbon synthon, vinyl biscyclopropanes (VBCPs), which undergoes Rh-catalyzed [8 + 1] cycloaddition with CO to furnish nine-membered carbocycles. This strategy enables the synthesis of 5/9 bicyclic compounds from VBCPs with diverse substituents. Mechanistic studies via quantum chemistry calculations revealed concerted C–C bond cleavages in the two cyclopropyl moieties of cis-VBCP substrates, whereas a stepwise pathway is adopted by trans-VBCPs. The key intermediate in the [8 + 1] cycloaddition is a nine-membered rhodacycle, which undergoes CO insertion followed by reductive elimination to deliver the desired nine-membered carbocycle. However, a competing β-H elimination pathway diverts the reaction, yielding a triene side product. For less effective or unsuccessful substrates, the sluggish CO insertion in the [8 + 1] cycloaddition pathway is attributed to the transannular interaction and unfavorable entropic effect during the formation of a challenging 10-membered rhodacycle in the CO insertion transition state, posing a similar obstacle for designing cycloadditions with ring sizes larger than nine.