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

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。

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.