Enantioselective Catalysis with Cyclopropenimines

环丙烯亚胺的对映选择性催化

• 批准号: 8974844
• 负责人: Tristan H Lambert
• 金额: $ 29.61万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-12-15 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8974844
• 关键词: Acidity; Address; Aerobic; Alkylation; Amines; Architecture; Area; Benzene; Biomedical Research; Catalysis; Catechols; Chromans; Complex; Development; Diamines; Effectiveness; Flavanones; Glycine; Glycols; Grant; Health; Hydroquinones; Imidazole; Investigation; Lead; Molecular; Nitrogen; Organic Synthesis; Outcome; Oxides; Phenols; Preparation; Prevalence; Production; Protons; Pyrazoles; Quinones; Reaction; Research; Series; Structure; System; Variant; Work; alkalinity; aqueous; base; catalyst; drug discovery; invention; programs; scaffold

DESCRIPTION (provided by applicant): Access to enantioenriched molecules is crucial to modern biomedical research. Many of the most important reactions in organic synthesis rely on proton transfer as a key mechanistic step. As such, chiral Bronsted base catalysis has emerged as a promising strategy for the production of valuable molecular building blocks in enantioenriched form. This area of catalysis has been impeded, however, by the relatively limited basicity of established catalyst platforms, which has significantly curtailed the widespread application of these approaches. Thus, there exists a clear impetus for the invention of new catalysts with increased potency and effectiveness, which could provide a general solution to the challenge of enantioselective Bronsted base catalysis. Toward this end, we have developed a fundamentally new class of highly reactive and enantioselective chiral Bronsted base catalyst, based on 2,3-bis(dialkylamino)cyclopropenimines. Notably, cyclopropenimines possess significantly higher basicity than established catalytic platforms. Based on our early demonstrations, we envision that cyclopropenimines may emerge as the definitive platform for enantioselective Bronsted base catalysis. Cyclopropenimines offer unique advantages of: (1) high basicity and reactivity; (2) ease of preparation; (3) compatibility with aqueous and aerobic conditions; (4) catalyst modularity; and (5) amenability to scale. In each of the projects targeted herein, we aim to apply cyclopropenimine catalysis to address a prominent challenge in organic synthesis. The asymmetric transformations targeted in this grant are either currently unknown or suffer from significant limitations of substrate scope. Among the specific reactions that we aim to develop in the context of this grant are: enantioselective glycine Mannich and α-thio Mannich reactions; α-arylations with quinones and benzene oxides; Michael additions with low acidity nucleophiles, including diazoesters; allylic alkylations; and enantioselective conjugate additions of phenols, amines, and nitrogen heterocycles. The development of these proposed transformations and the further establishment of the new cyclopropenimine catalyst platform will represent significant advances for the field of organic synthesis.

描述（适用提供）：访问对映体分子对于现代生物医学研究至关重要。有机合成中许多最重要的反应依赖于质子转移是关键的机械步骤。因此，手性Bronsted碱催化剂已成为以映射形式生产有价值的分子构建块的承诺策略。但是，这一催化型催化剂平台的相对有限的碱性阻碍了这一催化区域，这大大削弱了这些方法的宽度应用。这是有明显的动力，因为新催化剂的事故具有提高的效力和有效性，这可以为对映选择性布朗斯特德碱基催化的挑战提供一般的解决方案。为此，我们基于2,3-双（dialkylamino）环戊二胺开发了一类新的高度反应性和对映选择性手性Bronsted碱催化剂。值得注意的是，环丙烯亚胺潜力明显高于已建立的催化平台。基于我们的早期示范，我们设想环丙丙胺可以成为对映选择性Bronsted碱催化剂的确定平台。环丙烯胺具有：（1）高碱度和反应性的独特优势； （2）易于准备； （3）与水和有氧条件的兼容性； （4）催化剂模块化； （5）缩放的舒适性。在每个针对的项目中 本文中，我们旨在应用环丙二胺催化，以应对有机合成中的巨大挑战。该赠款中针对的不对称转换目前未知或受到底物范围的重大局限性。在我们旨在的具体反应中 喹酮和苯氧化物的α-包染；迈克尔添加低酸度核刺激性，包括重氮植物；大将酗酒；以及对映选择性共轭苯酚，胺和氮杂环的添加。这些提出的转化的发展以及新的环丙氨酸催化剂平台的进一步建立将代表有机合成领域的重大进步。