Toward and Around Nitrogen-Containing Molecules: Synthesis, Asymmetric Induction and Mechanistic Studies.

该项目的全球科学目标是研究各种含氮分子的合成、生物学和物理性质。C-N键的生成仍然是合成有机化学中的一个重要挑战，特别是手性胺的立体异构体的生成。含氮分子是一类重要的化合物研究，因为它们是生物活性分子的普遍成分；“超过75%的药物和候选药物含有胺的功能。”刘，科根，埃尔曼，j。化学。社会科学，1997,119,9913)。此外，许多表现出有趣性质的新型有机材料也含有氮原子。**我的团队一直对使用金属亚硝基物种来创建C-N键感兴趣。新型金属亚硝基前体，即n -甲酰基和n -甲酰基氧氨基甲酸酯，已被开发用于合成恶唑烷酮、氮嘧啶、苯基、烯丙基和丙基胺以及亚酰基亚胺。在许多情况下，立体选择反应是实现产生所需的手性含氮分子具有高水平的非对映选择性。这种化学的许多方面仍未被探索，本提案将解决这些未解决的领域。**用铑二聚体催化剂从磺基氨基甲酸酯进行分子内C-H胺化反应，产率高至高。然而，尽管我们和其他人做出了许多努力，但没有报道过这种反应的一般不对称版本。此外，铑是最昂贵的金属之一。我们最近确定铁配合物也可以催化这种反应，我们计划开发新的配体来诱导立体选择性。**我们最近开发了一种新的立体选择性方法来合成手性亚胺。目前合成亚胺类化合物的立体选择性方法很少，没有一种方法能提供高收率和立体选择性的脂肪衍生物。重要的是，最近在胶原蛋白IV网中发现了亚砜胺交联

The global scientific objective of this project is to study the synthesis, biological, and physical properties of various nitrogen-containing molecules. The creation of C-N bonds is still an important challenge in synthetic organic chemistry, especially to produce chiral amines as one stereoisomer. Nitrogen-containing molecules are an important class of compounds to study, as they are ubiquitous components of biologically active molecules; "greater than 75% of drugs and drug candidates incorporate amine functionality." (Liu, Cogan, Ellman, J. Am. Chem. Soc. 1997, 119, 9913). Furthermore, many novel organic materials that display interesting properties also incorporate nitrogen atoms.**My group has been interested at using metal nitrene species to create C-N bonds. Novel metal nitrene precursors, namely N-tosyl- and N-mesyl-oxycarbamates have been developed for the synthesis of oxazolidinones, aziridines, benzylic, allylic, and propargylic amines, as well as sulfilimines. In many cases, stereoselective reactions were achieved to produce the desired chiral nitrogen-containing molecules with high level of diastereoselectivity. There are many aspects of this chemistry that remain unexplored, and this proposal will address these unsolved areas.**Intramolecular C-H amination reactions from sulfonyoxycarbamates using rhodium dimer catalysts produced oxazolidinones in good to high yields. However, despite many efforts by us, and others, no general asymmetric version of this reaction has been reported. Furthermore, rhodium is among the most expensive metals. We have recently determined that iron complexes could also catalyze this reaction and we plan to develop novel ligands to induce stereoselectivities. **We have recently developed a novel stereoselective method to synthesize chiral sulfimines. Few stereoselective methods have been reported to synthesize sulfilimines, and none furnish aliphatic derivatives in high yield and stereoselectivity. Importantly, the recent discovery of sulfilimine crosslinks in collagen IV net