Department of Chemistry, University of California, Davis, California 95616, United States.
J Am Chem Soc. 2022 Sep 21;144(37):17219-17231. doi: 10.1021/jacs.2c07681. Epub 2022 Sep 13.
Rh-catalyzed C-H insertion reactions to form β-lactones suffer from post-transition state bifurcations, with the same transition states leading to ketones and ketenes via fragmentation in addition to β-lactones. In such a circumstance, traditional transition state theory cannot predict product selectivity, so we employed molecular dynamics simulations to do so and provide a framework for rationalizing the origins of said selectivity. Weak interactions between the catalyst and substrate were studied using energy decomposition and noncovalent interaction analyses, which unmasked an important role of the 2-bromophenyl substituent that has been used in multiple β-lactone-forming C-H insertion reactions. Small and large catalysts were shown to behave differently, with the latter providing a means of overcoming dynamically preferred fragmentation by lowering the barrier for the recombination of the product fragments in the grip of the large catalyst active site cavity.
铑催化的 C-H 插入反应形成β-内酰胺会受到过渡态后分叉的影响，相同的过渡态除了生成β-内酰胺外，还会通过断裂生成酮和烯酮。在这种情况下，传统的过渡态理论无法预测产物的选择性，因此我们采用分子动力学模拟来实现这一点，并为解释这种选择性的起源提供了一个框架。通过能量分解和非共价相互作用分析研究了催化剂和底物之间的弱相互作用，这揭示了在多个β-内酰胺形成的 C-H 插入反应中使用的 2-溴苯基取代基的重要作用。结果表明，小催化剂和大催化剂的行为不同，后者通过降低大催化剂活性位腔中产物碎片重排的势垒，为克服动态上优先的断裂提供了一种手段。
