A Multi-Component Strategy for the Synthesis of Complex Aliphatic Amines using Photo-redox Catalysis

利用光氧化还原催化合成复杂脂肪胺的多组分策略

• 批准号: EP/S020292/1
• 负责人: Matthew Gaunt
• 金额: $ 89.67万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FS020292%2F1
• 关键词: Multi; Component; Strategy; Synthesis; Complex

Alkylamines are ubiquitous amongst pharmaceuticals, small-molecule biological probes, natural products and pre-clinical candidates1. Despite their importance, amine synthesis is still dominated by two methods: N-alkylation and carbonyl reductive amination2. The increasing demand for 'sp3-rich' molecules in drug-discovery3 continues to drive development of practical catalytic methods to synthesize complex saturated alkylamines4-6. In particular, processes that transform diverse, readily-available feedstocks into structurally diverse sp3-rich architectures provides a strategic advantage in complex alkylamine synthesis. Here, we propose a multicomponent reductive photocatalytic technology that combines readily-available dialkylamines, carbonyls and radical acceptor feedstocks to build architecturally complex and functionally diverse tertiary alkylamines in a single step. This process involves a visible-light-mediated reduction of in-situ generated iminium ions, selectively furnishing previously inaccessible alkyl-substituted alpha-amino radicals, which engage radical acceptors and lead to C(sp3)-C(sp3) bond formation. The potential of this operationally straightforward reaction suggests a broad functional group tolerance, could facilitate the synthesis of drug-like amines not readily accessible by other methods and would be amenable to late-stage functionalization applications, making it of interest in pharmaceutical research and other areas.

烷基胺普遍存在于药物、小分子生物探针、天然产物和临床前候选物中1。尽管它们的重要性，胺合成仍然由两种方法主导：N-烷基化和羰基还原胺化2。在药物发现中对“富含sp3”分子的需求不断增加3继续推动合成复杂饱和烷基胺的实用催化方法的开发4 -6。特别地，将不同的、容易获得的原料转化为结构上不同的富含sp3的结构的方法在复杂的烷基胺合成中提供了战略优势。在这里，我们提出了一种多组分还原光催化技术，结合容易获得的二烷基胺，羰基和自由基受体原料，在一个单一的步骤中建立结构复杂和功能多样的叔烷基胺。该过程涉及原位生成的亚胺离子的可见光介导的还原，选择性地提供先前不可接近的烷基取代的α-氨基自由基，其接合自由基受体并导致C（sp3）-C（sp3）键的形成。这种操作简单的反应的潜力表明了广泛的官能团耐受性，可以促进合成药物样胺不容易通过其他方法获得，并将适合后期官能化应用，使其在药物研究和其他领域的兴趣。

项目成果

Thiol-Mediated a-Amino Radical Formation via Visible-Light-Activated Ion-Pair Charge-Transfer Complexes

通过可见光激活离子对电荷转移复合物形成硫醇介导的α-氨基自由基

• DOI: 10.17863/cam.78129
• 发表时间: 2021
• 作者: Kohara K

Visible light-mediated radical fluoromethylation via halogen atom transfer activation of fluoroiodomethane.

• DOI: 10.1039/d1sc04554g
• 发表时间: 2021-10-06
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Deneny PJ;Kumar R;Gaunt MJ
• 通讯作者: Gaunt MJ

Streamlined Synthesis of C(sp3)-Rich N-Heterospirocycles Enabled by Visible-Light-Mediated Photocatalysis

可见光介导光催化简化富 C(sp3) N-杂螺环的合成

• DOI: 10.17863/cam.43931
• 发表时间: 2019
• 作者: Flodén N

A Chiral Amine Transfer Approach to the Photocatalytic Asymmetric Synthesis of a-Trialkyl-a-tertiary Amines.

光催化不对称合成α-三烷基-α-叔胺的手性胺转移方法。

• DOI: 10.17863/cam.94546
• 发表时间: 2023
• 作者: Harris G

Modular Synthesis of alpha-Branched Secondary Alkylamines via Visible-light-mediated Carbonyl Alkylative Amination

可见光介导的羰基烷基胺化模块化合成α-支化仲烷基胺

• DOI: 10.26434/chemrxiv-2024-ng6c0
• 发表时间: 2024
• 作者: Gaunt M