Iron-Catalyzed Anti-Markovnikov Hydroamination and Hydroamidation of Allylic Alcohols

Journal of the American Chemical Society
Wei MaChao Wang

Abstract

Hydroamination allows for the direct access to synthetically important amines. Controlling the selectivity of the reaction with efficient, widely applicable, and economic catalysts remains challenging, however. This paper reports an iron-catalyzed formal anti-Markovnikov hydroamination and hydroamidation of allylic alcohols, which yields γ-amino and γ-amido alcohols, respectively. Homoallylic alcohol is also feasible. The catalytic system, consisting of a pincer Fe-PNP complex (1-4 mol %), a weak base, and a nonpolar solvent, features exclusive anti-Markovnikov selectivity, broad substrate scope (>70 examples), and good functional group tolerance. The reaction could be performed at gram scale and applied to the synthesis of drug molecules and heterocyclic compounds. When chiral substrates are used, the stereochemistry and enantiomeric excess are retained. Further application of the chemistry is seen in the functionalization of amino acids, natural products, and existing drugs. Mechanistic studies suggest that the reaction proceeds via two cooperating catalytic cycles, with the iron complex catalyzing a dehydrogenation/hydrogenation process while the amine substrate acts as an organocatalyst for the Michael addition step.

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Citations

Mar 20, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Arnar Guðmundsson, Jan-E Bäckvall
Apr 17, 2020·Chemistry : a European Journal·Timothy KwokTimothy James Donohoe
Mar 4, 2021·Organic & Biomolecular Chemistry·Zhuo ChenBang-Guo Wei
May 6, 2021·Organic & Biomolecular Chemistry·Chen LiZhen-Yuan Xu
Jun 1, 2021·ACS Central Science·Benjamin G Reed-BerendtLouis C Morrill
Jul 1, 2020·The Journal of Organic Chemistry·Vinod G LandgeEkambaram Balaraman
Dec 6, 2019·The Journal of Organic Chemistry·Murali Mohan GuruBiplab Maji
Oct 19, 2019·Organic Letters·Saki Ichikawa, Stephen L Buchwald
Nov 10, 2020·ACS Catalysis·Jacob M GanleyRobert R Knowles

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