Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Science. 2022 Jun 10;376(6598):1230-1236. doi: 10.1126/science.abp8488. Epub 2022 Jun 9.
The stereoselective synthesis of molecules bearing stereogenic phosphorus(V) centers represents an enduring challenge in organic chemistry. Although stereospecific nucleophilic substitution at P(V) provides a general strategy for elaborating optically active P(V) compounds, existing methods for accessing the requisite chiral building blocks rely almost entirely on diastereocontrol using chiral auxiliaries. Catalytic, enantioselective methods for the synthesis of synthetically versatile stereogenic P(V) building blocks offer an alternative approach to stereogenic-at-P(V) targets without requiring stoichiometric quantities of chiral control elements. Here, we report an enantioselective hydrogen-bond-donor-catalyzed synthesis of aryl chlorophosphonamidates and the development of these products as versatile chiral P(V) building blocks. We demonstrate that the two leaving groups on these chlorophosphonamidates can be displaced sequentially and stereospecifically to access a wide variety of stereogenic-at-P(V) compounds featuring diverse substitution patterns.
手性磷（V）中心的立体选择性合成是有机化学中一个持久的挑战。尽管磷（V）的立体特异性亲核取代为合成光学活性磷（V）化合物提供了一种通用策略，但获得必需的手性构建块的现有方法几乎完全依赖于使用手性助剂的非对映选择性控制。用于合成合成多功能立体手性磷（V）构建块的催化、对映选择性方法提供了一种替代方法，无需使用大量的手性控制元件即可获得立体手性磷（V）靶标。在这里，我们报告了一种氢键给体催化的芳基氯膦酰胺的对映选择性合成，以及这些产物作为多功能手性磷（V）构建块的发展。我们证明，这些氯膦酰胺上的两个离去基团可以顺序和立体特异性取代，以获得具有各种取代模式的各种立体手性磷（V）化合物。
