Catalytic Generation of Nucleophiles at Main Group Centres for Stereoselective Transformations

在立体选择性转化的主要基团中心催化生成亲核试剂

• 批准号: RGPIN-2017-04297
• 负责人: Speed, Alexander
• 金额: $ 4.81万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748101
• 关键词: Catalytic; Generation; Nucleophiles; Main; Group

Summary of Proposal Organic synthesis raises our quality of life by providing means to prepare fine chemicals used in medicine, materials and agriculture. Transformations in organic chemistry are often complicated by a lack of generality, or accompanied by the formation of undesired side products, consequently the development of new catalysts for fine chemical transformations continues to be an area of active investigation. My new research group at Dalhousie University is developing methodology employing catalysts synthesized from earth abundant main group elements to make synthesis cheaper, safer, and to make currently unknown transformations accessible, by providing complementary reactivity to catalysts derived from transition metals.We are exploring two promising themes, both of which develop new classes of nucleophiles based on main group centres with different and improved reactivity profiles to current technologies. One theme involves the hypothesis that borenium cations supported by bis(amino)cyclopropylidene (BAC) carbenes will display greater reactivity than known borenium cations because of the diminished steric bulk of BAC carbenes. We have already demonstrated that BAC carbene borenium cations are capable of hydrogenating substrates that are inaccessible to previously reported borenium cations. We will investigate the synthesis of chiral BAC carbene-supported borenium cations for asymmetric catalysis, including hydrogenation, aldol, and Diels- Alder reactions, all of vital importance in the synthesis of fine chemicals including pharmaceuticals. Our second theme involves the hypothesis that complexation of a heteroatom to a diazaphospholene raises the heteroatom's nucleophilicity. We have demonstrated that diazaphospholene alkoxides can catalyze imine reduction and conjugate reduction reactions. We will synthesize chiral diazaphospholenes with diverse architectures, and explore their ability to conduct catalytic activation and addition of nucleophiles other than hydride to conjugate acceptors and carbonyl compounds. The lack of Lewis acidity of diazaphospholenes renders them compatible with protic functional groups and Lewis basic functional groups, reducing the need for protecting groups, and potentially allowing the development of new strategies for functionalized molecule synthesis. The concepts we will develop from both themes will result in major impacts in synthetic chemistry through discovery of new reactivity. Catalysts such as those being developed in my group, that exhibit enhanced functional group tolerance, or allow transformations that are not currently accessible, allow steps to be cut in fine chemical synthesis. This streamlining will result in major environmental and financial savings, since fine chemical synthesis, especially pharmaceuticals, represent an industry worth hundreds of billions of dollars per year.

提案的摘要有机综合，通过提供用于医学，材料和农业中使用的精细化学物质的方法来提高我们的生活质量。有机化学的转化通常由于缺乏通用性而变得复杂，或者伴随着不希望的侧产物的形成，因此，开发新的催化剂以进行精细的化学转化，继续是一个积极研究的领域。我在Dalhousie大学的新研究小组正在开发方法，采用从地球丰富的主要小组元素合成的催化剂来使合成更便宜，更安全，并通过提供对从过渡金属衍生的催化剂的互补反应来使当前未知的转换访问。我们正在探索两种有希望的催化剂。主题，这两者都基于对当前技术的反应性概况不同和改善的反应性谱的主要组中心发展新的亲核者。一个主题涉及以下假设：BIS（氨基）环丙基丙烯（BAC）碳纤维支持的硼阳离子比已知的硼an阳离子的反应性更大，因为BAC碳纤维的大量减少。我们已经证明了BAC碳纤维硼阳离子能够氢化底物，这些底物无法以前报道的硼阳离子无法访问。我们将研究手性BAC碳纤维支持的硼牛阳离子的不对称催化，包括氢化，藻类和Diels-alder反应，这对于合成包括药物在内的精细化学物质的合成都至关重要。我们的第二个主题涉及这样的假设，即杂原子对二氮蛋白酶磷酸的络合会提高杂原子的亲核性。我们已经证明了二氮二磷氧化烷氧化物可以催化亚胺还原并偶联的还原反应。我们将与多种结构合成手性氮磷脂，并探索它们进行催化活化的能力，并添加除氢化物以外的氢化物以偶联受体和羰基化合物的能力。 Dizaphopholenes缺乏路易斯酸度使它们与原始官能团和刘易斯基本官能团兼容，从而减少了保护组的需求，并有可能允许开发新的官能化分子合成策略。 我们将从两个主题中提出的概念将通过发现新的反应性来对合成化学产生重大影响。诸如在我的小组中开发的催化剂，表现出增强的功能群耐受性，或允许当前无法访问的转换，允许在精细的化学合成中切开步骤。这种简化将导致大量的环境和财务节省，因为精细的化学合成，尤其是药品，代表着价值数千亿美元的行业。