Amino Acid Derived Chiral Aminobenzimidazole Manganese Catalysts for Asymmetric Transfer Hydrogenation of Ketones
Amino Acid Derived Chiral Aminobenzimidazole Manganese Catalysts for Asymmetric Transfer Hydrogenation of Ketones
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DOI：
10.1021/acscatal.1c00616
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发表时间：
2021-06
期刊：
影响因子：
12.9
通讯作者：
Lixian Wang;Jinlong Lin;Qiangsheng Sun;C. Xia;Wei Sun
中科院分区：
文献类型：
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作者：
Lixian Wang;Jinlong Lin;Qiangsheng Sun;C. Xia;Wei Sun
研究了一系列手性双齿苯并咪唑类Mn(I)催化剂。这些类型的无膦手性Mn催化剂在广泛的酮类底物的不对称转移加氢（ATH）中表现出高活性和对映选择性。体积较大的底物，如2,6-二氯-3-氟苯乙酮，可以以高达90%的收率和92%的ee（例如，克唑替尼）转化为药物中间体醇。在实验和DFT研究的基础上，提出了锰催化ATH的可能机理。DFT计算进一步给出了酮加氢过程中对映体控制的合理模型，其中催化剂和底物之间的π -π堆叠相互作用起着重要作用。
A series of Mn(I) catalysts with chiral bidentate benzimidazoles derived from easily available amino acids has been developed. These types of phosphine-free chiral Mn catalysts demonstrate high activity and enantioselectivity in asymmetric transfer hydrogenation (ATH) for a broad range of ketone substrates. A bulkier substrate, such as 2,6-dichloro-3-fluoroacetophenone, can be converted into the drug intermediate alcohol with up to 90% yield and 92% ee (e.g., crizotinib). On the basis of experimental and DFT studies, a possible mechanism for this Mn-catalyzed ATH is also proposed. DFT calculations further render a plausible model for enantiocontrol in ketone hydrogenation, in which the π–π stacking interaction between the catalyst and the substrate plays an important role.