State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Hong Kong, China.
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China.
Nat Chem. 2023 Dec;15(12):1672-1682. doi: 10.1038/s41557-023-01362-3. Epub 2023 Nov 16.
Stereoselective protonation is a challenge in asymmetric catalysis. The small size and high rate of transfer of protons mean that face-selective delivery to planar intermediates is hard to control, but it can unlock previously obscure asymmetric transformations. Particularly, when coupled with a preceding decarboxylation, enantioselective protonation can convert the abundant acid feedstocks into structurally diverse chiral molecules. Here an anchoring group strategy is demonstrated as a potential alternative and supplement to the conventional structural modification of catalysts by creating additional catalyst-substrate interactions. We show that a tailored benzamide group in aminomalonic acids can help build a coordinated network of non-covalent interactions, including hydrogen bonds, π-π interactions and dispersion forces, with a chiral acid catalyst. This allows enantioselective decarboxylative protonation to give α-amino acids. The malonate-based synthesis introduces side chains via a facile substitution of aminomalonic esters and thus can access structurally and functionally diverse amino acids.
立体选择性质子化是不对称催化中的一个挑战。质子的小尺寸和高迁移率意味着难以控制其向平面中间体的面选择性传递，但它可以解锁以前难以实现的不对称转化。特别是，当与前面的脱羧反应结合时，对映选择性质子化可以将丰富的酸原料转化为结构多样的手性分子。在这里，我们展示了一种锚固基团策略，作为通过创建额外的催化剂-底物相互作用来对催化剂进行常规结构修饰的潜在替代和补充。我们表明，在氨基丙二酸中引入定制的苯甲酰胺基团可以帮助建立非共价相互作用的配位网络，包括氢键、π-π相互作用和色散力，与手性酸催化剂相互作用。这允许对映选择性脱羧质子化生成α-氨基酸。基于丙二酸酯的合成通过氨基丙二酸酯的简单取代引入侧链，因此可以获得结构和功能多样的氨基酸。
