Copper-Catalyzed Asymmetric Hydrosilylation of β‑Nitroethyl Aryl Ketones
Weijun Zeng, Xuefeng Tan, Yang Yu, Gen-Qiang Chen, and Xumu Zhang*
Southern University of Science and Technology, Shenzhen, People’s Republic of China
—Organic Letters. 2020, DOI:10.1021/acs.orglett.9b04339
Recommended by Qilin Li_PDM
ABSTRACT: A copper-catalyzed asymmetric hydrosilylation of β- nitroethyl aryl ketones has been disclosed, and the corresponding chiral alcohols could be obtained in high yields (up to 99% yield) and excellent enantioselectivities (up to 96% ee). Moreover, the reaction worked well on a gram scale with 0.3 mol % of ligand loading, indicating that the protocol has potential applications in the synthesis of important pharmaceuticals such as Tranylcypromine and Ticagrelor.
General Synthetic Routes of the Cyclopropylamine.
Asymmetric Reduction of β-Nitroethyl Aryl Ketones.
(intramolecular SN2 strategy)
Optimization of the Reaction Conditions.
Ligands Screened for the Asymmetric Hydrosilylation.
•Axially chiral ligands such as L6, L7, L8 facilitate the reaction
•Chirality reverse when ligand converted
•Solvent play a very important role (Toluene work well, while n-heptane and i-PrOH kill the reaction)
•Temperature have influence on chirality as usualSubstrate Scope.
Summary and Comments:
In conclusion, Xumu Zhang and his co-workers have developed an efficient asymmetric hydrosilylation of β-nitroethyl aryl ketones, giving the corresponding chiral alcohols in high yields and enantioselectivities. This methodology provides a highly efficient access to the chiral trans-2-arylcyclopropylamine derivatives. Moreover, the reaction worked well on a gram scale with 0.3 mol % of ligand loading, indicating that the method has potential industrial applications in the synthesis of drugs and bioactive compounds.
High yield
High chiral purity
Cheap catalyst with low loading