Warren and Katharine Schlinger Laboratory of Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering , California Institute of Technology , Pasadena , California 91125 , United States.
Org Lett. 2019 Nov 15;21(22):9158-9161. doi: 10.1021/acs.orglett.9b03530. Epub 2019 Oct 31.
We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give -disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich -anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a -disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.
我们报告了钯催化的 1,4-二氮杂环庚烷-5-酮的不对称烯丙基烷基化反应。该反应能以高收率（高达 99%）和高对映选择性（高达 95%ee）顺利进行，得到带有各种官能团的取代的二氮杂环庚酮杂环。富电子的 -邻苯二甲酰基内酰胺保护基和非极性溶剂的使用被证明在大多数情况下对获得高对映选择性至关重要。此外，我们还展示了我们的方法在合成已获 FDA 批准的抗失眠药物苏沃雷生的 -二取代类似物中的应用。
