美国芝加哥大学董广彬团队报道了通过挂钩和滑动策略实现铑催化可调酰胺同源化。相关研究成果发表在2023年11月24日出版的《科学》期刊。

从铅化合物中制备各种同源物是药物化学中常见而重要的实践。然而，羧酸衍生物，特别是酰胺的同源化仍然具有挑战性。

该文中，研究人员报道了一种挂钩和滑动策略，用于具有可调长度的插入碳链的叔酰胺的同源性。在酰胺α-位置的烷基化（钩子）之后是高度选择性的支链到线性异构化（滑动），以使酰胺迁移到新引入的烷基链的末端；因此，烷基化试剂的选择决定了同源长度。关键步骤包括碳-碳键活化过程，该过程由卡宾配位的铑配合物在可移除的导向基团的帮助下进行。该方法被证明可引入长达16个碳的链，并适用于复杂生物活性分子中的衍生羧酸。

附：英文原文

Title: Rhodium catalyzed tunable amide homologation through a hook-and-slide strategy

Author: Rui Zhang, Tingting Yu, Guangbin Dong

Issue&Volume: 2023-11-24

Abstract: Preparation of diverse homologs from lead compounds has been a common and important practice in medicinal chemistry. However, homologation of carboxylic acid derivatives, particularly amides, remains challenging. Here we report a hook-and-slide strategy for homologation of tertiary amides with tunable lengths of the inserted carbon chain. Alkylation at the α-position of the amide (hook) is followed by highly selective branched-to-linear isomerization (slide) to effect amide migration to the end of the newly introduced alkyl chain; thus, the choice of alkylation reagent sets the homologation length. The key step involves a carbon-carbon bond activation process by a carbene-coordinated rhodium complex with assistance from a removable directing group. The approach is demonstrated for introduction of chains as long as 16 carbons and is applicable to derivatized carboxylic acids in complex bioactive molecules.

DOI: adk1001

Source: https://www.science.org/doi/10.1126/science.adk1001