Enantioselective Catalytic Chlorosilane Reactions

对映选择性催化氯硅烷反应

• 批准号: 10046812
• 负责人: Roberto Peverati
• 金额: $ 43.46万
• 依托单位: FLORIDA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10046812
• 关键词: 3-hydroxybutanal; Acetals; Alcohols; Amines; Antifungal Agents; Biological; Biology; Carbon; Catalysis; Charge; Chemicals; Complex; Development; Elements; Generations; Goals; Hand; Hydrogen; Investigation; Ketones; Knowledge; Methodology; Methods; Natural Products; Nature; Nitrogen; Organic Synthesis; Outcome; Oxygen; Performance; Peripheral; Pharmaceutical Chemistry; Pharmacologic Substance; Physical condensation; Play; Process; Propionates; Reaction; Reagent; Research; Role; Shapes; Silicon; Source; Structure; System; Time; Variant; Voriconazole; alkalinity; base; beta secretase; catalyst; chemical synthesis; density; design; drug development; drug discovery; in vivo; inhibitor/antagonist; innovation; insight; metabolic profile; method development; novel; novel therapeutics; prenylation; programs

Hypervalent silicon complexes generated from Lewis base catalysts and chlorosilanes are very reactive intermediates and continue to be an important source for the development of new chemical methodologies in organic synthesis. The unique reactivity profiles, non-toxicity and ready availability of chlorosilanes have yielded an impressive array of chemical methods and processes. This proposal seeks to innovate the ability of chlorosilanes to deliver carbon nucleophiles under Lewis base catalysis conditions through integrated experimental and computational investigations, and to apply it to novel condensation reactions with readily available non-activated ketones and ketimines. These challenging transformations will be rendered enantioselective through the development of conceptually new classes of chiral Lewis base catalysts. The utility of the resulting methods will be demonstrated by the asymmetric synthesis of pharmaceuticals and biologically relevant molecules. Goals of the research program include advancing Lewis base catalysis of chlorosilanes at the fundamental level, and new reaction development that will provide rapid, efficient access to novel chiral building blocks bearing the oxygen- and nitrogen-substituted quaternary stereocenters. We will focus on the transformations that can provide chiral synthetic intermediates that are either inaccessible or very difficult to obtain with currently available methods. The results are expected to transform the way chlorosilanes are utilized in asymmetric synthesis.

由路易斯碱催化剂和氯硅烷生成的高价硅配合物 是非常活泼的中间体，并且仍然是重要的来源 有机合成新化学方法的发展。独特的反应活性 氯硅烷的特性、无毒性和现成的可用性已经产生了令人印象深刻的结果 一系列化学方法和过程。该提案旨在创新能力 氯硅烷在路易斯碱催化条件下传递碳亲核试剂 通过综合实验和计算研究，并将其应用于 与容易获得的非活化酮和酮亚胺的新型缩合反应。 这些具有挑战性的转化将通过以下方式呈现对映选择性： 开发概念性新类别的手性路易斯碱催化剂。的效用 由此产生的方法将通过药物的不对称合成得到证明 和生物学相关的分子。该研究计划的目标包括推进 氯硅烷的路易斯碱催化基础水平和新反应 开发将提供快速、有效地获得新型手性结构单元 带有氧和氮取代的四元立构中心。我们将重点关注 可以提供手性合成中间体的转化是 用目前可用的方法无法获得或很难获得。结果是 预计将改变氯硅烷在不对称合成中的使用方式。

项目成果

Evaluation of 3,3'-Triazolyl Biisoquinoline N,N'-Dioxide Catalysts for Asymmetric Hydrosilylation of Hydrazones with Trichlorosilane.

评估 3,3-三唑基双异喹啉 N,N-二氧化物催化剂对腙与三氯硅烷的不对称氢化硅烷化反应。

• DOI: 10.3390/catal11091103
• 发表时间: 2021
• 期刊: Catalysts (Basel, Switzerland)
• 作者: Sun,Shiyu;Xu,Changgong;Jarvis,Jamielyn;Nader,Phillip;Naumann,Brandon;Soliven,Abigail;Peverati,Roberto;Takenaka,Norito
• 通讯作者: Takenaka,Norito

Asymmetric Catalytic Ketimine Mannich Reactions and Related Transformations.

不对称催化酮亚胺曼尼希反应和相关转化。

• DOI: 10.3390/catal11060712
• 发表时间: 2021
• 期刊: Catalysts (Basel, Switzerland)
• 作者: Xu,Changgong;Reep,Carlyn;Jarvis,Jamielyn;Naumann,Brandon;Captain,Burjor;Takenaka,Norito
• 通讯作者: Takenaka,Norito

Evaluation of helicene-derived 2,2'-bipyridine N-monoxide catalyst for the enantioselective propargylation of N-acylhydrazones with allenyltrichlorosilane.

• DOI: 10.1016/j.tet.2023.133496
• 发表时间: 2023-07
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Chang Xu;Phillip Nader;J. Xavier;B. Captain;N. Takenaka

Steps toward Rationalization of the Enantiomeric Excess of the Sakurai-Hosomi-Denmark Allylation Catalyzed by Biisoquinoline N,N'-Dioxides Using Computations.

使用计算合理化双异喹啉 N,N-二氧化物催化的 Sakurai-Hosomi-Denmark 烯丙基化对映体过量的步骤。

• DOI: 10.3390/catal11121487
• 发表时间: 2021
• 期刊: Catalysts (Basel, Switzerland)
• 作者: Morgante,Pierpaolo;Deluca,Coty;Jones,TeglaE;Aldrich,GregoryJ;Takenaka,Norito;Peverati,Roberto
• 通讯作者: Peverati,Roberto

Design and synthesis of 3,3'-triazolyl biisoquinoline N,N'-dioxides via Hiyama cross-coupling of 4-trimethylsilyl-1,2,3-triazoles.

通过 4-三甲基甲硅烷基-1,2,3-三唑的 Hiyama 交叉偶联设计和合成 3,3-三唑基二异喹啉 N,N-二氧化物。

• DOI: 10.1016/j.tetlet.2021.153338
• 发表时间: 2021
• 期刊: Tetrahedron letters
• 影响因子: 1.8
• 作者: Sun,Shiyu;Reep,Carlyn;Zhang,Chenrui;Captain,Burjor;Peverati,Roberto;Takenaka,Norito
• 通讯作者: Takenaka,Norito