Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory, 106 91 Stockholm, Sweden.
School of Chemistry and Physics, University of Kwazulu-Natal, Private Bag X54001, Durban 4000, South Africa.
J Am Chem Soc. 2021 Dec 29;143(51):21594-21603. doi: 10.1021/jacs.1c09573. Epub 2021 Dec 14.
We present a highly efficient convergent asymmetric hydrogenation of / mixtures of enamides catalyzed by N,P-iridium complexes supported by mechanistic studies. It was found that reduction of the olefinic isomers ( and geometries) produces chiral amides with the same absolute configuration (enantioconvergent hydrogenation). This allowed the hydrogenation of a wide range of / mixtures of trisubstituted enamides with excellent enantioselectivity (up to 99% ). A detailed mechanistic study using deuterium labeling and kinetic experiments revealed two different pathways for the observed enantioconvergence. For α-aryl enamides, fast isomerization of the double bond takes place, and the overall process results in kinetic resolution of the two isomers. For α-alkyl enamides, no double bond isomerization is detected, and competition experiments suggested that substrate chelation is responsible for the enantioconvergent stereochemical outcome. DFT calculations were performed to predict the correct absolute configuration of the products and strengthen the proposed mechanism of the iridium-catalyzed isomerization pathway.
我们提出了一种高效的、通过 N，P-铱络合物催化的、对酰胺混合物的不对称催化氢化反应。通过动力学实验和氘标记实验的深入研究，我们发现顺式烯烃异构体（和 构型）的还原生成了具有相同绝对构型的手性酰胺（对映体一致氢化）。这使得一系列的三取代酰胺及其混合物能够在高对映选择性下进行氢化（最高可达 99%）。详细的动力学研究揭示了两种不同的反应途径，从而导致观察到的对映体一致氢化。对于α-芳基酰胺，双键的快速异构化发生，整个过程导致两个异构体的动力学拆分。对于α-烷基酰胺，没有检测到双键异构化，竞争实验表明底物螯合是导致对映体一致立体化学结果的原因。进行了密度泛函理论计算，以预测产物的正确绝对构型，并加强所提出的铱催化异构化途径的机制。
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