Department of Chemistry, University of York, York, YO10 5DD, UK.
ENSICAEN, 6 Boulevard Maréchal Juin, CS 45053, 14050, Caen Cedex 04, France.
Chemistry. 2020 Oct 1;26(55):12674-12683. doi: 10.1002/chem.202002164. Epub 2020 Sep 11.
The outcome of ring-expansion reactions based on amino/hydroxyacid side-chain insertion is strongly dependent on ring size. This manuscript, which builds upon our previous work on Successive Ring Expansion (SuRE) methods, details efforts to better define the scope and limitations of these reactions on lactam and β-ketoester ring systems with respect to ring size and additional functionality. The synthetic results provide clear guidelines as to which substrate classes are more likely to be successful and are supported by computational results, using a density functional theory (DFT) approach. Calculating the relative Gibbs free energies of the three isomeric species that are formed reversibly during ring expansion enables the viability of new synthetic reactions to be correctly predicted in most cases. The new synthetic and computational results are expected to support the design of new lactam- and β-ketoester-based ring-expansion reactions.
基于氨基酸/羟基酸侧链插入的环扩张反应的结果强烈依赖于环的大小。本手稿建立在我们之前关于连续环扩张（SuRE）方法的工作基础上，详细说明了努力更好地定义这些反应在环大小和附加功能方面对内酰胺和β-酮酯环系统的范围和限制。合成结果为哪些底物类别更有可能成功提供了明确的指导，并得到了使用密度泛函理论（DFT）方法的计算结果的支持。计算在环扩张过程中可逆形成的三种异构物种的相对吉布斯自由能，使得在大多数情况下能够正确预测新的合成反应的可行性。新的合成和计算结果有望支持新的基于内酰胺和β-酮酯的环扩张反应的设计。
