Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion.
Evaluating the Viability of Successive Ring-Expansions Based on Amino Acid and Hydroxyacid Side-Chain Insertion.
复制标题
评估基于氨基酸和羟基酸侧链插入的连续环跨疗法的生存能力。
DOI：
10.1002/chem.202002164
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发表时间：
2020-10-01
期刊：
影响因子：
--
通讯作者：
Unsworth WP
中科院分区：
文献类型：
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作者：
Lawer A;Epton RG;Stephens TC;Palate KY;Lodi M;Marotte E;Lamb KJ;Sangha JK;Lynam JM;Unsworth WP
基于氨基/羟基酸侧链插入的扩环反应的结果强烈依赖于环的大小。这份手稿建立在我们之前关于连续扩环（SuRE）方法的工作基础上，详细介绍了在环大小和附加功能方面更好地定义内酰胺和β-酮酯环系统上这些反应的范围和限制的努力。合成结果提供了明确的指导方针，基板类更有可能是成功的，并支持计算结果，使用密度泛函理论（DFT）的方法。计算的相对吉布斯自由能的三个异构体的物种，在环膨胀过程中可逆地形成，使新的合成反应的可行性，以正确地预测在大多数情况下。新的合成和计算结果有望支持新的内酰胺和β-酮酯扩环反应的设计。 戒指合适吗？基于氨基/羟基酸侧链插入的环扩张强烈依赖于环大小。在此，提供了关于哪些环系统更有可能成功的指南。合成结果得到了计算化学的支持。计算膨胀过程中形成的同分异构体的相对吉布斯自由能有助于预测新反应的可行性。
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. Does the ring fit? Ring expansions based on amino/hydroxyacid side‐chain insertion are strongly dependent on ring size. Herein, guidelines are provided on which ring systems are more likely to be successful. Synthetic results are supported by computational chemistry. Calculating the relative Gibbs free energies of isomeric species formed during expansion helps predict the viability of new reactions.