Roger Adams Laboratory, Department of Chemistry , University of Illinois , Urbana , Illinois 61801 , United States.
J Am Chem Soc. 2019 Jun 19;141(24):9468-9473. doi: 10.1021/jacs.9b02690. Epub 2019 Jun 5.
We report the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone system that enables unprecedented access to anti-1,3 amino alcohol motifs in good yields (33 substrates, avg. 66% isolated yield, >20:1 dr) and high selectivities (avg. 10:1 dr). Switching ligands to (±)-CF-SOX with the use of a less bulky quinone oxidant, the kinetic syn-1,3 amino alcohol motif can be accessed in comparable yields and selectivities. Advantages of the stereodivergent nature of this reaction are seen in the synthesis of anti- and syn-1,3 amino alcohol vitamin D3 analogue intermediates in half the steps and higher overall yield relative to previous routes. Additionally, all eight possible stereoisomers of a chiral diamino alcohol core are generated from two amino acids. Mechanistic studies reveal that the anti-isomer is furnished through concurrent Pd(II)(SOX) catalyzed C-H amination and Pd(0)(SOX) catalyzed isomerization cycles.
我们报告了 Pd(II)/(±)-MeO-SOX/2,5-二甲基苯醌体系的发展，该体系能够以良好的收率（33 个底物，平均 66%的分离产率，>20:1 dr）和高选择性（平均 10:1 dr）获得前所未有的反式-1,3 氨基醇基序。将配体切换为（±）-CF-SOX，并使用体积较小的醌氧化剂，可以以相当的产率和选择性获得动力学 syn-1,3 氨基醇基序。该反应的立体发散性质的优势体现在反式和 syn-1,3 氨基醇维生素 D3 类似物中间体的合成中，相对于以前的路线，步骤减半，总收率更高。此外，两个氨基酸可以生成手性二氨基醇核心的全部八个可能的立体异构体。机理研究表明，反式异构体是通过同时进行的 Pd(II)(SOX)催化的 C-H 氨化和 Pd(0)(SOX)催化的异构化循环生成的。
