Department of Chemistry, University of California, Berkeley, California 94720, United States.
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.
J Am Chem Soc. 2020 Apr 1;142(13):6390-6399. doi: 10.1021/jacs.0c01637. Epub 2020 Mar 23.
Herein we report the first highly enantioselective allenoate-Claisen rearrangement using doubly axially chiral phosphate sodium salts as catalysts. This synthetic method provides access to β-amino acid derivatives with vicinal stereocenters in up to 95% ee. We also investigated the mechanism of enantioinduction by transition state (TS) computations with DFT as well as statistical modeling of the relationship between selectivity and the molecular features of both the catalyst and substrate. The mutual interactions of charge-separated regions in both the zwitterionic intermediate generated by reaction of an amine to the allenoate and the Na-salt of the chiral phosphate leads to an orientation of the TS in the catalytic pocket that maximizes favorable noncovalent interactions. Crucial arene-arene interactions at the periphery of the catalyst lead to a differentiation of the TS diastereomers. These interactions were interrogated using DFT calculations and validated through statistical modeling of parameters describing noncovalent interactions.
在此，我们报告了首例使用双轴向手性磷酸钠盐作为催化剂的高对映选择性丙二烯酯-Claisen重排反应。这种合成方法可以获得具有相邻立体中心的β-氨基酸衍生物，对映体过量值高达 95%。我们还通过密度泛函理论（DFT）对反应过渡态（TS）的诱导机制进行了研究，并对选择性与催化剂和底物分子特征之间关系进行了统计建模。手性磷酸钠与胺反应生成的两性离子中间体中的电荷分离区域之间的相互作用，以及手性磷酸钠中的电荷分离区域之间的相互作用，导致 TS 在催化口袋中的取向最大化了有利的非共价相互作用。催化剂外围的关键芳烃-芳烃相互作用导致 TS 非对映异构体的区分。这些相互作用通过 DFT 计算进行了检验，并通过描述非共价相互作用的参数的统计建模进行了验证。
