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. 2018 Jul 6;8(7):5907-5914.
doi: 10.1021/acscatal.8b00711. Epub 2018 May 11.

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

Zhishi Ye #  1 , Xinpei Cai #  1 , Jiawei Li  1 , Mingji Dai  1
Affiliations

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

Zhishi Ye et al. ACS Catal. .

Abstract

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.

Keywords: copper catalysis; cyclopropanol; quaternary carbon; ring opening; α,β-unsaturated enone; γ-butyrolactone; δ-ketoester.

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Figures

Figure 1.
Figure 1.
Prior arts and this work.
Figure 2.
Figure 2.
Mechanistic studies. aYield based on 1H NMR analysis with 1,3,5-trimethoxybenzene as internal reference.
Figure 3.
Figure 3.
Proposed reaction mechanism for the formation of 12 and 13.
See this image and copyright information in PMC

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