Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
J Am Chem Soc. 2010 Mar 3;132(8):2775-83. doi: 10.1021/ja9097803.
This study demonstrates that unsaturated acyl phosphonates are excellent hydrogen-bond acceptors in enantioselective organocatalysis. By employing chiral thioureas or squaramides as catalysts, the acyl phosphonates are effectively coordinated and activated by hydrogen bonding, thereby providing successful relay of the chirality from the catalyst to the substrate. A variety of highly stereoselective conjugate additions to alpha,beta-unsaturated acyl phosphonates were performed, using different carbon-based nucleophiles such as oxazolones, indoles, and 1,3-dicarbonyl compounds. The reaction concept has been developed to be a double nucleophilic reaction, and it is shown that the acyl phosphonates serve as masked ester or amide equivalents, which upon quenching with the second nucleophile generate the parent structures in situ. Accordingly, formal C-C bond formation reactions of ester and amide substrates are achieved, affording a broad spectrum of optically active conjugate adducts in good yields and excellent enantioselectivities. Based on the experimental results, the mechanisms for the different reactions are discussed, including the approach of the oxazolones, indoles, and 1,3-dicarbonyl compounds to the acyl phosphonate coordinated to the catalyst and the role of the catalyst for the reaction course of the nucleophiles.
本研究表明，不饱和膦酸酯是手性有机催化中优异的氢键受体。通过使用手性硫脲或螺二酰胺作为催化剂，膦酸酯通过氢键有效地配位和活化，从而成功地将手性从催化剂传递到底物。使用不同的碳亲核试剂，如噁唑酮、吲哚和 1,3-二羰基化合物，对α,β-不饱和膦酸酯进行了多种高对映选择性的共轭加成反应。该反应概念已被开发为双亲核反应，结果表明膦酸酯作为掩蔽酯或酰胺等价物，与第二种亲核试剂淬灭后原位生成母体结构。因此，酯和酰胺底物的正式 C-C 键形成反应得以实现，以良好的产率和优异的对映选择性获得了广泛的光学活性共轭加合物。基于实验结果，讨论了不同反应的机理，包括噁唑酮、吲哚和 1,3-二羰基化合物与与催化剂配位的膦酸酯的接近方式，以及催化剂在手性亲核试剂反应过程中的作用。
