Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group.

08:00 EDT 10th March 2020 | BioPortfolio

Summary of "Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Cyclobutyl Ketones Using a Chiral Transient Directing Group."

The utilization of chiral transient directing groups (TDGs) has recently emerged as a promising approach for developing Pd(II)-catalyzed enantioselective C( sp 3 )-H activation reactions. However, this strategy is particularly challenging because the stereogenic center present on the TDG is often far from the C-H bond. Additionally, the TDG covalently attached to the substrate and the free TDG are both capable of coordinating to Pd(II) centers, which can result in a mixture of reactive complexes that may lead to opposite asymmetric induction. To date, the single example of TDG-enabled enantioselective C( sp 3 )-H activation is limited to the functionalization of benzylic C-H bonds. Herein we report the first example of a Pd(II)-catalyzed enantioselective β-C( sp 3 )-H arylation reaction of aliphatic ketones using a chiral transient directing group. A chiral trisubstituted cyclobutane is efficiently synthesized from a monosubstituted cyclobutane via sequential C-H arylation reactions, demonstrating the ability of this method to access structurally complex products from simple starting materials. The use of an electron-deficient pyridone ligand is also crucial for the observed high enantioselectivity. Interestingly, employing different silver salts can reverse the enantioselectivity in the C( sp 3 )-H arylation reaction. These key mechanistic findings will provide insight for future development of Pd(II)-catalyzed enantioselective C( sp 3 )-H activation reactions with chiral TDGs.


Journal Details

This article was published in the following journal.

Name: Angewandte Chemie (International ed. in English)
ISSN: 1521-3773


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