Carbenoid Pathways in Copper-Catalyzed Intramolecular Cyclopropanations of Phenyliodonium Ylides

Abstract

The enantioselectivity of the copper-catalyzed intramolecular cyclopropanation of allyl diazomalonates and the corresponding phenyliodonium ylides was investigated with a series of chiral, non-racemic ligands. The reaction of 6b in the presence of the bis[dihydrooxazole] ligand Xa in refluxing 1,2-dichloroethane proceeded to 8b with an enantiomer excess (ee) of up to 72% under optimized conditions. In contrast, 8b resulting from reaction of ylide 7b with the same ligand, but in CH2Cl2 at 0°, had an ee of only 30%. With other ligands, diazomalonate 6b reacted with a lower enantioselectivity than ylide 7b, however. The intramolecular cyclopropanation of the acetoacetate-derived phenyliodonium ylide 15b afforded 16b with 68% ee with ligand Xa, but the corresponding diazo compound was unreactive when exposed to chiral copper catalysts. The observation of asymmetric induction in the Cu-catalyzed reactions of the ylides 7 and 15 is consistent with a carbenoid mechanism; however, the discrepancy of the enantioselectivities observed between diazomalonate 6b and ylide 7b suggests a competing unselective pathway for cyclopropanation outside of the coordination sphere of copper.