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

含氮分子及其周围：合成、不对称诱导和机理研究。

• 批准号: RGPIN-2014-05281
• 负责人: Lebel, Hélène
• 金额: $ 3.93万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=656905
• 关键词: Toward; Around; Nitrogen; Containing; Molecules

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

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，特别是作为一个立体异构体来生产手性胺。含氮分子是一类需要研究的重要化合物，因为它们是生物活性分子中无处不在的成分；“超过75%的药物和候选药物具有胺功能。”(刘，科根，埃尔曼，J.Am化学。SoC。1997、119、9913)。此外，许多具有有趣性质的新型有机材料也加入了氮原子。**我的团队一直对使用金属氮物种来创建C-N键感兴趣。为合成恶唑烷酮、氮杂环丙烷、苄基、烯丙基和丙叉胺以及磺胺类化合物，开发了新型金属硝基前体，即N-对甲苯磺酰氧基氨基甲酸酯和N-甲磺酰氧基氨基甲酸酯。在许多情况下，立体选择性反应被实现以产生所需的具有高水平非对映选择性的手性含氮分子。这一化学仍有许多方面尚未探索，这项建议将解决这些未解决的领域。**磺酰氧基氨基甲酸酯在铑二聚体催化剂上的分子内C-H胺化反应以良好到高的产率生成恶唑烷酮。然而，尽管我们和其他人做了很多努力，这种反应的一般不对称版本还没有报道。此外，铑是最昂贵的金属之一。我们最近已经确定，铁配合物也可以催化这一反应，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。磺胺类化合物的立体选择性合成方法很少，也没有高产率和立体选择性的脂肪族衍生物的报道。重要的是，最近在IV型胶原网络中发现了磺胺交联物