Schenk Stephan, Weston Jennie, Anders Ernst
Institut für Organische Chemie und Makromolekulare Chemie der Friedrich-Schiller-Universität, Humboldtstrasse 10, D-07743 Jena, Germany.
J Am Chem Soc. 2005 Sep 14;127(36):12566-76. doi: 10.1021/ja052362i.
In this article we performed an extensive density functional [BP86/6-311++G(3df,3pd) level] investigation of the hypersurface of the Mitsunobu reaction. Reaction of a phosphine with a dialkyl azodicarboxylate (first step in the Mitsunobu conversion) leads to either a five-membered oxadiazaphosphole ring (more stable) or a betaine. The subsequent formation of two stable intermediates, a dialkoxyphosphorane and an acyloxyalkoxyphosphorane, constitutes the second step in the mechanism. These intermediates are in equilibrium with each other (under exchange of alkoxy and acyloxy ligands), and both can undergo an acid-induced decomposition to yield the alkoxy- and/or acyloxyphosphonium salts. The alkoxyphosphonium salt generates the desired ester via a SN2 mechanism (inversion product). Alternatively, the phosphorus atom in a mixed acyloxyalkoxyphosphorane species can easily undergo Berry pseudorotation. A subsequent intramolecular substitution leads to the final ester via a retention mechanism. The hypersurface is much more complicated than previously assumed, and the Mitsunobu reaction is fundamentally capable of running under either inversion or retention. The possibility of selective stereocontrol is discussed. Side reactions include the formation of a degradation product and an anhydride.
在本文中，我们对光延反应的超曲面进行了广泛的密度泛函研究（BP86/6-311++G(3df,3pd) 水平）。膦与偶氮二甲酸二烷基酯的反应（光延转化的第一步）会生成一个五元恶二氮磷杂环（更稳定）或一个内盐。随后形成两种稳定的中间体，即二烷氧基磷烷和酰氧基烷氧基磷烷，这是该反应机理的第二步。这些中间体相互处于平衡状态（在烷氧基和酰氧基配体交换的情况下），并且两者都可以发生酸诱导的分解，生成烷氧基和/或酰氧基鏻盐。烷氧基鏻盐通过SN2机理生成所需的酯（构型翻转产物）。或者，混合的酰氧基烷氧基磷烷物种中的磷原子可以很容易地发生贝里假旋转。随后的分子内取代通过构型保留机理生成最终的酯。该超曲面比之前假设的要复杂得多，并且光延反应从根本上能够在构型翻转或构型保留的情况下进行。文中讨论了选择性立体控制的可能性。副反应包括降解产物和酸酐的形成。
