Asymmetric Hydrogenation of α-Substituted Acrylic Acids Catalyzed by a Ruthenocenyl Phosphino-oxazoline-Ruthenium Complex.
Asymmetric hydrogenation of various α-substituted acrylic acids was carried out using RuPHOX-Ru as a chiral catalyst under 5 bar H2, affording the corresponding chiral α-substituted propanic acids in up to 99% yield and 99.9% ee. The reaction could be performed on a gram-scale with a relatively low catalyst loading (up to 5000 S/C), and the resulting product (97%, 99.3% ee) can be used as a key intermediate to construct bioactive chiral molecules. The asymmetric protocol was successfully applied to an asymmetric synthesis of dihydroartemisinic acid, a key intermediate required for the industrial synthesis of the antimalarial drug artemisinin.
School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
Jing
J
Li
School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
Jiefeng
J
Shen
School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
Chao
C
Xia
School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
Yanzhao
Y
Wang
School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
Delong
D
Liu
School of Pharmacy and ‡School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University , 800 Dongchuan Road, Shanghai 200240, China.
Wanbin
W
Zhang