Catalytic enantioselective intermolecular desymmetrization of azetidines.
The first catalytic asymmetric desymmetrization of azetidines is disclosed. Despite the low propensity of azetidine ring opening and challenging stereocontrol, smooth intermolecular reactions were realized with excellent efficiency and enantioselectivity. These were enabled by the suitable combination of catalyst, nucleophile, protective group, and reaction conditions. The highly enantioenriched densely functionalized products are versatile precursors to other useful chiral molecules. Mechanistic studies, including DFT calculations, revealed that only one catalyst molecule is involved in the key transition state, though both reactants can be activated. Also, the Curtin-Hammett principle dictates the reaction proceeds via amide nitrogen activation.
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Zhaobin
Z
Wang
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Fu Kit
FK
Sheong
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Herman H Y
HH
Sung
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Ian D
ID
Williams
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Zhenyang
Z
Lin
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Jianwei
J
Sun