Iron‐Catalyzed Highly Enantioselective cis‐Dihydroxylation of Trisubstituted Alkenes with Aqueous H2O2

• Published in: Angewandte Chemie International Edition Vol. 59; no. 38; pp. 16561 - 16571
• Main Authors: Wei, Jinhu, Wu, Liangliang, Wang, Hai‐Xu, Zhang, Xiting, Tse, Chun‐Wai, Zhou, Cong‐Ying, Huang, Jie‐Sheng, Che, Chi‐Ming
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 14.09.2020
• Edition: International ed. in English
• Subjects: Alkenes; Catalysts; Diamines; Diols; Enantiomers; homogeneous catalysis; Hydrogen peroxide; hydroxylation; Iron; Ligands; nitrogen ligands; NMR; Nuclear magnetic resonance; Oxidants; Oxidizing agents; trisubstituted alkenes
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202002866

Reliable methods for enantioselective cis‐dihydroxylation of trisubstituted alkenes are scarce. The iron(II) complex cis‐α‐[FeII(2‐Me2‐BQPN)(OTf)2], which bears a tetradentate N4 ligand (Me2‐BQPN=(R,R)‐N,N′‐dimethyl‐N,N′‐bis(2‐methylquinolin‐8‐yl)‐1,2‐diphenylethane‐1,2‐diamine), was prepared and characterized. With this complex as the catalyst, a broad range of trisubstituted electron‐deficient alkenes were efficiently oxidized to chiral cis‐diols in yields of up to 98 % and up to 99.9 % ee when using hydrogen peroxide (H2O2) as oxidant under mild conditions. Experimental studies (including 18O‐labeling, ESI‐MS, NMR, EPR, and UV/Vis analyses) and DFT calculations were performed to gain mechanistic insight, which suggested possible involvement of a chiral cis‐FeV(O)2 reaction intermediate as an active oxidant. This cis‐[FeII(chiral N4 ligand)]2+/H2O2 method could be a viable green alternative/complement to the existing OsO4‐based methods for asymmetric alkene dihydroxylation reactions. Trisubstituted alkenes undergo Fe‐catalyzed asymmetric cis‐dihydroxylation (AD) with H2O2 to give cis‐diols in up to 98 % yield and with up to >99.9 % ee. This Fe catalyst/H2O2 AD method is applicable to a variety of trisubstituted alkenes bearing electron‐withdrawing substituents, such as ester and amide groups. Mechanistic studies by 18O‐labeling, UV/Vis spectroscopy, ESI‐MS, NMR spectroscopy, EPR spectroscopy, and DFT calculations were performed.