Binaphthol-Derived Bisphosphoric Acids Serve as Efficient Organocatalysts for Highly Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylides to Electron-Deficient Olefins
Binaphthol-Derived Bisphosphoric Acids Serve as Efficient Organocatalysts for Highly Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylides to Electron-Deficient Olefins
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联萘酚衍生的二磷酸作为高效有机催化剂，用于偶氮甲碱叶立德与缺电子烯烃的高对映选择性 1,3-偶极环加成反应
DOI：
10.1021/ja204218h
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发表时间：
2011-08-31
影响因子：
15
通讯作者：
Gong, Liu-Zhu
中科院分区：
文献类型：
--
作者：
He, Long;Chen, Xiao-Hua;Gong, Liu-Zhu
以联萘酚衍生的手性双磷酸为催化剂，对1，3-偶极环加成反应的立体选择性进行了研究，发现催化剂中连接基团的性质对反应的立体选择性有很大的影响。其中，氧连接的二磷酸Ia提供了最高水平的立体选择性的1，3-偶极环加成反应耐受广泛的底物，包括甲亚胺叶立德，从广泛的醛和α-氨基酯原位生成，和各种缺电子亲偶极体，如马来酸酯，马来酸酯，乙烯基酮，和酯。该反应实际上代表了获得具有优异光学纯度的结构多样的吡咯烷的最具对映选择性的催化方法之一。用密度泛函理论（DFT）方法对偶氮甲碱叶立德的形成和1，3-偶极环加成反应的过渡态进行了理论计算，结果表明，偶极和亲偶极试剂同时被双官能手性双磷酸通过氢键的形成而活化.双磷酸对三组分1，3-偶极环加成反应的反应活性和立体化学的影响也从理论上得到了合理的解释。双磷酸催化剂Ia可以呈现半月形，其中两个磷酸基团形成两个分子内氢键。在马来酸酯的情况下，一个磷酸酯充当碱以活化1，3-偶极，并且同时，催化剂Ia中的两个羟基可以分别与马来酸酯的两个酯基形成两个氢键，以使其作为强得多的亲偶极体更缺电子，从而参与与甲亚胺叶立德的协同1，3-偶极环加成。然而，在涉及丙烯酸酯和富马酸酯亲偶极试剂的情况下，仅一个羟基与酯官能团形成氢键以降低C-C双键的LUMO，并且另一个羟基保留以调节两个磷酸的酸碱性以更有效地活化偶极和亲偶极试剂。
A variety of chiral bisphosphoric acids derived from binaphthols have been evaluated for enantioselective 1,3-dipolar cycloaddition reactions, revealing that the feature of the linker in the catalysts exerted great impact on the stereoselectivity. Among them, the oxygen-linked bisphosphoric acid la provided the highest level of stereoselectivity for the 1,3-dipolar cycloaddition reaction tolerating a wide range of substrates including azomethine ylides, generated in situ from a broad scope of aldehydes and alpha-amino esters, and various electron-deficient dipolarophiles such as maleates, fumarates, vinyl ketones, and esters. This reaction actually represents one of the most enantioselective catalytic approaches to access structurally diverse pyrrolidines with excellent optical purity. Theoretical calculations with DFT method on the formation of azomethine ylides and on the transition states of the 1,3-dipolar cycloaddition step showed that the dipole and dipolarophile were simultaneously activated by the bifunctional chiral bisphosphoric acids through the formation of hydrogen bonds. The effect of the bisphosphoric acids on reactivity and stereochemistry of the three-component 1,3-dipolar cycloaddition reaction was also theoretically rationalized. The bisphosphoric acid catalyst la may take on a half-moon shape with the two phosphoric acid groups forming two intramolecular hydrogen bonds. In the case of maleates, one phosphate acts as a base to activate the 1,3-dipole, and simultaneously, the two hydroxyl groups in the catalyst la may respectively form two hydrogen bonds with the two ester groups of maleate to make it more electronically deficient as a much stronger dipolarophile to participate in a concerted 1,3-dipolar cyclo addition with azomethine ylide. However, in the cases involving acrylate and fumarate dipolarophiles, only one hydroxyl group forms a hydrogen bond with the ester functional group to lower the LUMO of the C-C double bond and another one is remained to adjust the acidity and basicity of two phosphoric acids to activate the dipole and dipolarophile more effectively.