Catalytic Cyclopropanol Ring Opening for Divergent Syntheses of γ‑Butyrolactones and δ‑Ketoesters Containing All-Carbon Quaternary Centers

Catalytic ring opening
cross coupling reactions of strained cyclopropanols
have been useful for the syntheses of various β-substituted
carbonyl products. Among these ring opening cross coupling reactions,
the formation of α,β-unsaturated enone byproducts often
competes with the desired cross coupling processes and has been a
challenging synthetic problem to be addressed. Herein, we describe
our efforts in developing divergent syntheses of a wide range of γ-butyrolactones
and δ-ketoesters containing all-carbon quaternary centers via
copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-dialkyl
esters. Our mechanistic studies reveal that unlike the previously
reported cases, the formation of α,β-unsaturated enone
intermediates is actually essential for the γ-butyrolactone
synthesis and also contributes to the formation of the δ-ketoester
product. The γ-butyrolactone synthesis is proposed to go through
an intermolecular radical conjugate addition to the in situ generated
α,β-unsaturated enone followed by an intramolecular radical
cyclization to the ester carbonyl double bond. The reactions are effective
to build all-carbon quaternary centers and have broad substrate scope.