Cobalt-catalysed desymmetrization of malononitriles via enantioselective borohydride reduction.

Autor: Zheng Y; State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong, China., Yang T; Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China., Chan KF; State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong, China., Lin Z; Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China. chzlin@ust.hk., Huang Z; State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong, China. huangzx@hku.hk.
Jazyk: angličtina
Zdroj: Nature chemistry [Nat Chem] 2024 Nov; Vol. 16 (11), pp. 1845-1854. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1038/s41557-024-01592-z
Abstrakt: The high nitrogen content and diverse reactivity of malononitrile are widely harnessed to access nitrogen-rich fine chemicals. Although the facile substitutions of malononitrile can give structurally diverse quaternary carbons, their access to enantioenriched molecules, particularly chiral amines that are prevalent in bioactive compounds, remains rare. Here we report a cobalt-catalysed desymmetric reduction of disubstituted malononitriles to give highly functionalized β-quaternary amines. The pair of cobalt salt and sodium borohydride is proposed to generate a cobalt-hydride intermediate and initiate the reduction. Meanwhile, the enantiocontrol of the dinitrile is achieved through a tailored bisoxazoline ligand with two large flanks that create a narrow gap to host the bystanding nitrile and thus restrict the C(ipso)-C(α) bond rotation of the complexed one. Combined with the extensive derivatization possibilities of all substituents on the quaternary carbon, this asymmetric reduction unlocks pathways from malononitrile as a bulk chemical feedstock to intricate, chiral nitrogen-containing molecules.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
Externí odkaz: