Department of Chemistry, Wesleyan University , Middletown, Connecticut 06459, United States.
J Org Chem. 2017 Aug 4;82(15):7946-7956. doi: 10.1021/acs.joc.7b01200. Epub 2017 Jul 25.
Thiol-Michael "click" reactions are essential synthetic tools in the preparation of various materials including polymers, dendrimers, and other macromolecules. Despite increasing efforts to apply thiol-Michael chemistry in a controlled fashion, the selectivity of base- or nucleophile-promoted thiol-Michael reactions in complex mixtures of multiple thiols and/or acceptors remains largely unknown. Herein, we report a thorough fundamental study of the selectivity of thiol-Michael reactions through a series of 270 ternary reactions using H NMR spectroscopy to quantify product selectivity. The varying influences of different catalysts/initiators are explored using ternary reactions between two Michael acceptors and a single thiol or between a single Michael acceptor and two thiols using three different catalysts/initiators (triethylamine, DBU, and dimethylphenylphosphine) in chloroform. The results from the ternary reactions provide a platform from which sequential quaternary, one-pot quaternary, and sequential senary thiol-Michael reactions were designed and their selectivities quantified. These results provide insights into the design of selective thiol-Michael reactions that can be used for the synthesis and functionalization of multicomponent polymers and further informs how catalyst/initiator choice influences the reactivity between a given thiol and Michael acceptor.
硫醇-迈克尔“点击”反应是制备各种材料（包括聚合物、树枝状大分子和其他聚合物）的重要合成工具。尽管人们越来越努力地以可控的方式应用硫醇-迈克尔化学，但在多种硫醇和/或受体的复杂混合物中，碱或亲核试剂促进的硫醇-迈克尔反应的选择性在很大程度上仍然未知。在此，我们通过一系列使用 NMR 光谱定量产物选择性的 270 个三元反应，对硫醇-迈克尔反应的选择性进行了全面的基础研究。使用三种不同的催化剂/引发剂（三乙胺、DBU 和二甲基苯基膦）在氯仿中，通过两种迈克尔受体和一种硫醇之间的三元反应或一种迈克尔受体和两种硫醇之间的三元反应，探索了不同催化剂/引发剂的不同影响。三元反应的结果为设计顺序四元、一锅四元、顺序六元硫醇-迈克尔反应提供了一个平台，并对其选择性进行了量化。这些结果为设计选择性硫醇-迈克尔反应提供了思路，可用于多组分聚合物的合成和功能化，并进一步说明催化剂/引发剂的选择如何影响给定硫醇和迈克尔受体之间的反应性。
