Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, NO-0315 Oslo, Norway.
J Org Chem. 2010 Mar 5;75(5):1620-9. doi: 10.1021/jo902585j.
Polymer-supported chiral organocatalysts, as well as most other forms of immobilized catalysts, are traditionally prepared by a postmodification approach where modified catalyst precursors are anchored onto prefabricated polymer beads. Herein, we report an alternative and more scalable approach where polymer-supported chiral enamine and iminium organocatalysts are prepared in a bottom-up fashion where methacrylic functional monomers are prepared in an entirely nonchromatographic manner and subsequently copolymerized with suitable comonomers to give cross-linked polymer beads. All syntheses have been conducted on multigram scale for all intermediates and finished polymer products, and the catalysts have proven successful in reactions taking place in solvents spanning a wide range of solvent polarity. While polymer-supported proline and prolineamides generally demonstrated excellent results and recycling robustness in asymmetric aldol reactions of ketones and benzaldehydes, the simplest type of Jørgensen/Hayashi diarylprolinol TMS-ether showed excellent selectivity, but rather sluggish reactivity in the Enders-type asymmetric cascade. The polymer-supported version of the first-generation MacMillan imidazolidinone had a pattern of reactivity very similar to that of the monomeric catalyst, but is too unstable to allow recycling.
聚合物负载手性有机催化剂，以及大多数其他形式的固定化催化剂，传统上是通过后修饰方法制备的，即将改性的催化剂前体锚定到预制的聚合物珠上。在此，我们报告了一种替代的、更具扩展性的方法，其中聚合物负载的手性烯胺和亚胺有机催化剂是通过自下而上的方式制备的，其中甲基丙烯酸功能单体以完全非色谱的方式制备，然后与合适的共聚单体共聚得到交联聚合物珠。所有合成均在多克规模上进行，用于所有中间体和最终聚合物产品，并且催化剂已成功用于在溶剂极性范围广泛的溶剂中进行的反应。虽然聚合物负载脯氨酸和脯氨酸酰胺在酮和苯甲醛的不对称羟醛反应中通常表现出优异的结果和回收稳定性，但最简单类型的 Jørgensen/Hayashi 二芳基脯醇 TMS-醚表现出优异的选择性，但在 Enders 型不对称级联反应中反应性相当缓慢。第一代 MacMillan 咪唑烷酮的聚合物负载形式的反应性模式与单体催化剂非常相似，但不稳定到无法进行回收。
