Kazerouni Amaan M, Brandes Daniel S, Davies Cassondra C, Cotter Laura F, Mayer James M, Chen Shuming, Ellman Jonathan A
Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
Department of Chemistry and Biochemistry, Oberlin College, Oberlin, Ohio 44074, United States.
ACS Catal. 2022 Jul 1;12(13):7798-7803. doi: 10.1021/acscatal.2c02232. Epub 2022 Jun 16.
Most known methods to access δ-lactams with stereogenic centers at the α- and β-positions are highly selective for the contra-thermodynamic diastereomer, typically hydrogenation of the corresponding pyridinones or quinolinones. We describe here the development of a photoredox-mediated hydrogen atom transfer (HAT) approach for the epimerization of δ-lactams to access the more stable diastereomers from the contra-thermodynamic isomers. The reaction displays broad functional group compatibility, including acid, ester, 1°, 2° and 3° amide, carbamate, and pyridyl groups, and was effective for a range of differently substituted monocyclic and bicyclic lactams. Experimentally observed diastereoselectivities are consistent with the calculated relative stabilities of lactam diastereomers. Convergence to the same diastereomer ratio from the - and - diastereomers establishes that reversible epimerization provides an equilibrium mixture of diastereomers. Additionally, deuterium labeling and luminescence quenching studies shed further light on the mechanism of the reaction.
大多数已知的用于合成在α和β位带有手性中心的δ-内酰胺的方法，对于反热力学非对映异构体具有高度选择性，典型的方法是相应吡啶酮或喹啉酮的氢化反应。我们在此描述了一种光氧化还原介导的氢原子转移（HAT）方法，用于δ-内酰胺的差向异构化，以从反热力学异构体获得更稳定的非对映异构体。该反应表现出广泛的官能团兼容性，包括酸、酯、伯酰胺、仲酰胺和叔酰胺、氨基甲酸酯和吡啶基，并且对一系列不同取代的单环和双环内酰胺均有效。实验观察到的非对映选择性与计算得到的内酰胺非对映异构体的相对稳定性一致。从 - 和 - 非对映异构体收敛到相同的非对映异构体比例，表明可逆差向异构化提供了非对映异构体的平衡混合物。此外，氘标记和发光猝灭研究进一步揭示了反应机理。
