Development of heterogeneous catalyst systems for the continuous synthesis of chiral amines via asymmetric hydrogenation
Development of heterogeneous catalyst systems for the continuous synthesis of chiral amines via asymmetric hydrogenation
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DOI：
10.1038/s41929-019-0371-y
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发表时间：
2019-11
期刊：
影响因子：
37.8
通讯作者：
T. Yasukawa;Ryusuke Masuda;S. Kobayashi
中科院分区：
文献类型：
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作者：
T. Yasukawa;Ryusuke Masuda;S. Kobayashi
精细化学品的连续流合成在环境相容性、效率和安全性方面比间歇合成具有多种优势。尽管如此，大多数制备方法仍然依赖于传统的批处理系统。例如，手性胺是药物化合物中普遍存在的功能，但具有广泛底物通用性的连续合成方法仍然非常具有挑战性。在这里，我们展示了与手性磷酸结合的异质铱配合物的开发，用于亚胺的不对称氢化，以实现手性胺的连续合成。使用相同的催化剂体系，在氢气氛下酮的直接不对称还原胺化也顺利进行。可以以高产率和高对映选择性制备各种手性芳香胺和脂肪胺，包括药物中间体。研究发现，使用填充有异质铱络合物的柱的连续流动反应甚至在比相应间歇反应低的压力下连续两天以上连续提供手性胺。
Continuous-flow synthesis of fine chemicals has several advantages over batch synthesis in terms of environmental compatibility, efficiency and safety. Nevertheless, most preparative methods still rely on conventional batch systems. For instance, chiral amines are ubiquitous functionalities in pharmaceutical compounds, but methods for their continuous synthesis with broad substrate generality remain very challenging. Here we show the development of heterogeneous iridium complexes combined with chiral phosphoric acids for the asymmetric hydrogenation of imines towards the continuous synthesis of chiral amines. Direct asymmetric reductive amination of ketones under a hydrogen atmosphere also proceeded smoothly using the same catalyst systems. Various chiral aromatic and aliphatic amines including pharmaceutical intermediates could be prepared in high yields with high enantioselectivities. It was found that continuous-flow reactions that use columns packed with the heterogeneous iridium complexes afforded chiral amines continuously for more than two days even at pressures lower than those in the corresponding batch reactions.