Narczyk Aleksandra, Stecko Sebastian
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Org Biomol Chem. 2020 Aug 5;18(30):5972-5981. doi: 10.1039/d0ob01315c.
A method for the preparation of enantiopure β-tert-amino alcohols bearing a tetrasubstituted C-stereocenter, as well as their conversion into selected medicinally privileged heterocyclic systems (morpholines, aziridines, piperazines) is reported. These compounds were obtained through enantiospecific sigmatropic rearrangement of allyl carbamates as a key step. The latter were prepared from the corresponding β,β'-dialkyl-substituted non-racemic allyl alcohols. In addition, an asymmetric synthesis of such highly substituted allylic alcohols via either enantioselective 1,2-reduction of enones, enzymatic kinetic resolution, or a functionalization of chiral propargyl alcohols, with discussion of scope and limitations of each method is reported.
报道了一种制备带有四取代C-立体中心的对映体纯β-叔氨基醇的方法，以及将其转化为选定的具有药用价值的杂环体系（吗啉、氮丙啶、哌嗪）的方法。这些化合物是通过烯丙基氨基甲酸酯的对映选择性[3,3] - 迁移重排作为关键步骤获得的。后者由相应的β,β'-二烷基取代的非外消旋烯丙醇制备。此外，还报道了通过烯酮的对映选择性1,2-还原、酶促动力学拆分或手性炔丙醇的官能化来不对称合成此类高度取代的烯丙醇，并讨论了每种方法的适用范围和局限性。
