In the past two years, Zhong-Yan had always involved in the use of intramolecular EDA complex to design new catalytic asymmetric methods for the preparation of biological active molecules preparation. After extensive studies, the researcher has finally identified that the crucial for success is inspired from the Melchiorre group’s previous finding1 that the bifunctional carbaozle amine catalyst can generate, upon condensation with enones, chiral iminium ions, which bears intramolecular EDA moiety and shows a broad absorption band in the visible region. Under the supervision of Prof. Dr. Melchiorre and generous support of ICIQ, the researcher demonstrates for the first time, that an intramolecular EDA complex can be used for designing useful asymmetric methodology.
The strategy allows the much easier assemble of biologically active chiral molecules, comparing with the reported methods (for details, please see picture 2). For instance, compound A has been patented due to the prevention of ophthalmic disease.2 However, as documented, starting from α-ketone ester, it needs seven steps to get the racemic A with only 1.2% total yield. In sharp contrast, with our methodology as the key step, the procedure can not only be shortened to 2 steps, but also give rise to the enantioenriched (R)-A in 57% total yield. On the other hand, product B can be easily prepared from commercial available 3,5,5-trimethylcyclohex-2-en-1-one, and the following highly diastereoselective reduction using L-selectride led to trans-alcohol C with 71% ee. Giving that the bioactivity of cis-C for the treatment and prevention of influenza,3 the prepared trans-C could be potentially helpful for the related biological activity test. These interesting results have been submitted to the peer-reviewed high impact chemistry journal and will be open access after publication.
1 J. J. Murphy, D. Bastida, S. Paria, M. Fagnoni and P. Melchiorre, Nature 2016, 532, 218.
2 T. Quach, J. Berman and D. S. Garvey, 2013, WO 2013/081642 A1.
3 L. Chen, X. Lin, Z. Qiu, G. Tang, L. Wang, J. Wu and W. Yang, 2011, WO 2011/095576 A1.
