Cobalt-Catalyzed Asymmetric Aza-Nozaki-Hiyama-Kishi (NHK) Reaction of α-Imino Esters with Alkenyl Halides

Tingting Xia; Yinhui Wu; Jiangtao Hu; Xianqing Wu; Jingping Qu; Yifeng Chen

doi:10.1002/anie.202316012

Cobalt-Catalyzed Asymmetric Aza-Nozaki-Hiyama-Kishi (NHK) Reaction of α-Imino Esters with Alkenyl Halides

Angew Chem Int Ed Engl. 2024 Feb 12;63(7):e202316012. doi: 10.1002/anie.202316012. Epub 2024 Jan 12.

Authors

Tingting Xia¹, Yinhui Wu¹, Jiangtao Hu¹, Xianqing Wu¹, Jingping Qu¹, Yifeng Chen^{1

2}

Affiliations

¹ Key Laboratory for Advanced Materials, Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
² State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, P. R. China.

PMID: 38164694
DOI: 10.1002/anie.202316012

Abstract

Chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi (NHK) reaction represents one of the most powerful approaches for the formation of chiral carbon-heteroatom bond. However, the construction of sterically encumbered tetrasubstituted stereocenter through NHK reaction still posts a significant challenge. Herein, we disclose a cobalt-catalyzed aza-NHK reaction of ketimine with alkenyl halide to provide a convenient synthetic approach for the manufacture of enantioenriched tetrasubstituted α-vinylic amino acid. This protocol exhibits excellent functional group tolerance with excellent 99 % ee in most cases. Additionally, this asymmetric reductive method is also applicable to the aldimine to access the trisubstituted stereogenic centers.

Keywords: Alkenyl Halide; Amino Acid Derivatives; Asymmetric Catalysis; Cobalt; NHK Reaction.

Abstract

Grants and funding