Supplementary materials for PhD thesis "A Cycloaddition Route to Pyrrolidines"

This dataset comprises the files contained on a CD-ROM which was attached to the thesis when it was submitted in 2007. It was uploaded to ORDO in 2024 for preservation purposes. For more information, please refer to the thesis A Cycloaddition Route to Pyrrolidines via ORO.Thesis abstractThe work presented in this thesis focuses on the development of base-free 1,3-dipolar cycloaddition reactions of azomethine ylides to produce homochiral pyrrolidines. Previous work within our group has shown the suitability of using 1-benzyl-4,5-dihydroimidazole as the starting point for the generation of an azomethine ylide that undergoes 1,3-dipolar cycloadditions with a range of dipolarophiles in a highly regio- and stereoselective fashion.l-Benzyl-2-imidazoline reacts with ethyl diazoacetate in the presence of Cu(acac)2 to form an azomethine ylide that reacts with dimethyl fumarate to yield a hexahydropyrrolo[1,2-a] imidazole. Similarly, the 2-imidazoline reacts with diazoacetate and fumaronitrile in the presence of copper(II) triflate to form analogous bicyclic systems. Other Cu(II) salts were found to be less effective catalysts, as was the Rh(II) acetate dimer.In the course of the above reactions, we isolated two diastereomeric products that proved to be 1:2 adducts between the dihydroimidazole and the electron deficient alkene. These compounds also contained the hexahydropyrrolo[ 1,2-a] imidazole core and their formation can be rationalised by (i) a Michael-type addition of the dihydroimidazole onto one molecule of the electron-deficient alkene to form a 1,3-zwitterion, (ii) a 1,2-proton shift within the zwitterion to form an azomethine ylide, and (iii) 1,3-dipolar cycloaddition of the ylide onto a second alkene molecule acting as a dipolarophile. Other electron-deficient alkenes, e.g. maleate, maleimides and fumaronitrile also undergo this reaction but ethyl cinnamate and p-nitrostyrene do not.The reaction with a mixture of two alkenes allows 1:1:1 products to be isolated. In these situations maleimides act as the Michael acceptor and the second alkene as the dipolarophile. In this way we found the order of reactivity to be maleimide > fumarate/maleate ester > fiimaronitrile. The stereochemistry of the four new chiral centres was elucidated by X-ray crystallography and n.O.e. difference spectroscopy. The formation of the major diastereoisomer can be rationalised by a transition-state model in which (i) the a-carbonyl of the ylide is syn to the 2-H of the dihydroimidazole, (ii) the dipolarophile approaches in an endo fashion. Formation of the minor diastereomer may involve a subsequent épimérisation at the C7a position of the fused system or endo mode of attack on the alternative ylide rotamer. Incorporation of a chiral centre into the imidazoline through the use of a phenyl substituent affords complete facial selectivity for the 1,3-dipolar cycloaddition reaction.Some electron-deficient systems that are unable to participate in the 1,2-proton shift (e.g.DMAD, β-nitrostyrene) form 1:2 adducts in which the product contains a 5,6-fused system. These products can be understood as arising from two sequential Michael additions to form a 1,5-zwiterion that is able to ring close onto the imidazoline iminium ion.

本数据集包含了2007年提交论文时附带的CD-ROM中存储的文件。为了保存目的，该数据集于2024年上传至ORDO。如需更多信息，请参阅论文《通过ORO的环加成途径合成吡咯烷》。论文摘要：本论文所展示的研究工作集中于开发无碱基1,3-偶极环加成反应，以亚甲基亚胺亚乙基为反应物，生成同构型吡咯烷。本研究小组先前的工作已表明，以1-苄基-4,5-二氢咪唑为起点生成亚甲基亚胺亚乙基，能够以高度的区域和立体选择性方式与多种偶极亲电子体发生1,3-偶极环加成反应。l-苄基-2-咪唑啉在Cu(acac)2的存在下与乙基重氮乙酸酯反应，生成亚甲基亚胺亚乙基，该亚乙基与顺丁烯二酸二甲酯反应，得到六氢吡咯[1,2-a]咪唑。类似地，2-咪唑啉在铜(II)三氟化物的存在下与重氮乙酸酯和富马腈反应，形成类似的双环系统。其他Cu(II)盐被证明是效果较差的催化剂，同样，铑(II)乙酸盐二聚体也是如此。在上述反应过程中，我们分离出了两种对映异构体产物，这些产物被证明是二氢咪唑和电子缺乏烯烃之间的1:2加合物。这些化合物也含有六氢吡咯[1,2-a]咪唑核心，其形成可以通过以下方式进行解释：（i）二氢咪唑对电子缺乏烯烃的一个分子进行Michael型加成，形成1,3-亚胺离子，（ii）在亚胺离子中进行1,2-质子转移，形成亚甲基亚胺亚乙基，（iii）亚乙基对第二个烯烃分子作为偶极亲电子体进行1,3-偶极环加成。其他电子缺乏烯烃，例如顺丁烯二酸、马来酰亚胺和富马腈，也经历此反应，但乙基肉桂酸和p-硝基苯乙烯则不参与。与两种烯烃混合物的反应可以分离出1:1:1的产物。在这些情况下，马来酰亚胺作为Michael受体，第二个烯烃作为偶极亲电子体。我们发现反应活性的顺序为：马来酰亚胺 > 顺丁烯二酸/顺丁烯二酸酯 > 富马腈。通过X射线晶体学和n.O.e.差分光谱，阐明了四个新手性中心的立体化学。主要对映异构体的形成可以通过一个过渡态模型进行解释，其中（i）亚乙基的α-羰基与二氢咪唑的2-H位处于顺式，（ii）偶极亲电子体以内式方式接近。次要对映异构体的形成可能涉及融合系统C7a位置的后续epimérisation或对替代亚乙基顺式异构体的内式攻击。通过使用苯基取代基将手性中心引入咪唑中，为1,3-偶极环加成反应提供了完整的面选择性。一些不能参与1,2-质子转移的电子缺乏系统（例如DMAD、β-硝基苯乙烯）形成1:2加合物，其中产物含有5,6-融合系统。这些产物可以理解为通过两个连续的Michael加成形成1,5-亚胺离子，该亚胺离子能够环合到咪唑的亚胺离子上。