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Cobalt-Catalyzed Diastereo- and Enantioselective Hydroalkylation of Cyclopropenes with Cobalt Homoenolates
Update time: 2021-05-06
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Catalytic asymmetric hydrofunctionalization of cyclopropenes is one of the most efficient strategies for the rapid and diverse synthesis of chiral multi-substituted cyclopropanes. It has been reported that the use of high-activity organometallic reagents, such as Grignard reagents, organozinc reagents, organoaluminum reagents, etc., can introduce simple alkyl groups without functional groups on cyclopropene, while the asymmetric functionalization of cyclopropene using reagents with high functional group compatibility but low reactivity is rarely reported. Chiral multi-substituted cyclopropane is a common structural fragment in biologically active drug molecules and natural products. Therefore, it is necessary to develop catalytic asymmetric functionalization of cyclopropenes using reagents with good functional group compatibility and through a reaction process with high atom economy.

The Meng Fanke group of the State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, has been committed to the study of cobalt-catalyzed asymmetric reactions. In the previous research, Meng Fanke’s research group discovered that the low-cost, easily available, high-functional group-compatible alkenyl boronic acid with different substitution types under the action of cobalt(II)/bisphosphine and potassium carbonate can efficiently generate alkenyl cobalt species, and then undergo an asymmetric hydroalkenylation reaction with cyclopropene, constructing chiral alkenyl cyclopropane products with high diastereoselectivity and enantioselectivity. (Angew. Chem. Int. Ed. 2019, 58, 11049 –11053)

Recently, new research progress had been made by the Meng group. They used cobalt(II)-catalyzed β-carbon-carbon bond cleavage of the cyclopropanol to generate the cobalt homoenolate complex for the asymmetric hydrofunctionalization of cyclopropane. (Angew. Chem. Int. Ed. 2021, 60, 2694–2698)

They found that the cobalt homoenolate intermediate is more reactive than boric acid due to the coordination of the carbonyl group, and the reaction can be carried out efficiently even under cooling conditions. This reaction has excellent yield and wide substrate applicability and 100% atomic economy to introduce the carbonyl-containing alkyl group to cyclopropenes in one step. Alkenyl and ester substituted cyclopropanols, which are rarely studied in the β-carbon-carbon bond cleavage reaction, are also suitable for this reaction. Mechanism studies have shown that the protonation process of the carbon-cobalt bond is a rate-determining-step, and there is no racemization of the carbon-cobalt bond during the protonation process. Moreover, the cobalt homoenolate complex will undergo a reversible enolization process. The reaction product can undergo subsequent functional group conversion, and the ketone carbonyl group can be selectively converted into an ester group or an amino group, which facilitates the rapid construction of a chiral cyclopropane compound library.

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