Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, China.
Angew Chem Int Ed Engl. 2019 Feb 25;58(9):2854-2858. doi: 10.1002/anie.201813381. Epub 2019 Feb 6.
Chiral phosphines were found to catalyze the enantioselective asymmetric γ-addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)-BINOL. Both pyrazole and imidazole could be employed in this process. The synthetic value of these γ-addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds. Remarkably, the synthetic utility of this strategy was demonstrated through a two-step synthesis of a Janus kinase (JAK) inhibitor.
手性膦配体被发现能够在(S)-BINOL 的存在下，以高对映选择性和区域选择性催化杂芳族化合物与丙二烯酸酯的对映选择性不对称γ-加成，得到高产率的产物。在这个过程中，吡唑和咪唑都可以被使用。这些γ-加成产物的合成价值通过制备具有生物相关性的分子和结构骨架得到了证明。值得注意的是，通过两步合成 Janus 激酶 (JAK) 抑制剂，展示了该策略的合成实用性。
