Chicago Tri-Institutional Center for Chemical Methods and Library Development, Department of Chemistry, University of Chicago, Chicago, Illinois 60637, USA.
Nat Chem. 2011 Dec 4;4(1):45-51. doi: 10.1038/nchem.1212.
Multicomponent reactions are employed extensively in many areas of organic chemistry. Despite significant progress, the discovery of such enabling transformations remains challenging. Here, we present the development of a parallel, label-free reaction-discovery platform that can be used in the identification of new multicomponent transformations. Our approach is based on parallel mass spectrometric screening of interfacial chemical reactions on arrays of self-assembled monolayers. This strategy enabled the identification of a simple organic phosphine that can catalyse a previously unknown condensation of siloxyalkynes, aldehydes and amines to produce 3-hydroxyamides with high efficiency and diastereoselectivity. The reaction was further optimized using solution-phase methods.
多组分反应在有机化学的许多领域中得到了广泛应用。尽管已经取得了显著的进展，但发现这种促进转化的方法仍然具有挑战性。在这里，我们提出了一种平行的、无标记的反应发现平台的开发，该平台可用于鉴定新的多组分转化。我们的方法基于在自组装单层阵列上进行界面化学反应的平行质谱筛选。这种策略能够鉴定出一种简单的有机膦，它可以催化以前未知的硅氧炔、醛和胺的缩合反应，以高效率和立体选择性生成 3-羟基酰胺。该反应进一步通过溶液相方法进行了优化。
