Department of Chemistry, University of Alberta, T6G 2G2, Edmonton, Alberta, Canada.
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 100029, Beijing, China.
Chemistry. 2023 Jun 27;29(36):e202300727. doi: 10.1002/chem.202300727. Epub 2023 May 3.
Stereodivergent dual catalysis has emerged as a powerful tool to selectively prepare all four stereoisomers in molecules containing two chiral centers from common starting materials. Most processes involve the use of two substrates, and it remains challenging to use dual catalyst approaches to generate molecules having three newly formed stereocenters with high diastereo- and enantioselectivity. Here we report a multicomponent, stereodivergent method for the synthesis of targets containing three contiguous stereocenters by the combination of enantioselective Rh-catalyzed conjugate addition and Ir-catalyzed allylic alkylation methodologies. Both cyclic and acyclic α,β-unsaturated ketones undergo β-arylation using aryl boron reagents to form an enolate nucleophile that can be subsequently allylated at the α-position. The reactions proceed often with >95 % ee and with >90 : 10 dr. Epimerization at the α-carbonyl center enables the preparation of any of the eight possible stereoisomers from common starting materials, as demonstrated for cyclohexanone products.
立体发散双催化已成为一种强大的工具，可从常见的起始原料中选择性地制备含有两个手性中心的分子中的所有四个立体异构体。大多数过程都涉及使用两种底物，而使用双催化剂方法来高非对映选择性和对映选择性地生成具有三个新形成的立体中心的分子仍然具有挑战性。在这里，我们报告了一种多组分、立体发散的方法，通过组合对映选择性 Rh 催化的共轭加成和 Ir 催化的烯丙基烷基化方法，来合成含有三个连续立体中心的目标物。环状和非环状的 α,β-不饱和酮都可以使用芳基硼试剂进行β-芳基化，形成烯醇化物亲核试剂，然后可以在α-位进行烯丙基化。反应通常以 >95%的 ee 和 >90:10 的 dr 进行。α-羰基中心的外消旋化使得可以从常见的起始原料制备任何八种可能的立体异构体，环己酮产物证明了这一点。
