Ma Hui-Chao, Sun Ya-Nan, Chen Gong-Jun, Dong Yu-Bin
College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University Jinan 250014 P. R. China
Chem Sci. 2022 Jan 14;13(7):1906-1911. doi: 10.1039/d1sc06045g. eCollection 2022 Feb 16.
The catalytic asymmetric α-benzylation of aldehydes represents a highly valuable reaction for organic synthesis. For example, the generated α-heteroarylmethyl aldehydes, such as ()-2-methyl-3-(pyridin-4-yl)propanal (()-MPP), are an important class of synthons to access bioactive drugs and natural products. We report herein a new and facile synthetic approach for the asymmetric intermolecular α-benzylation of aldehydes with less sterically hindered alkyl halides using a multifunctional chiral covalent framework (CCOF) catalyst in a heterogeneous way. The integration of chiral BINOL-phosphoric acid and Cu(ii)-porphyrin modules into a single COF framework endows the obtained ()-CuTAPBP-COF with concomitant Brønsted and Lewis acidic sites, robust chiral confinement space, and visible-light induced photothermal conversion. These features allow it to highly promote the intermolecular asymmetric α-benzylation of aldehydes visible-light induced photothermal conversion. Notably, this light-induced thermally driven reaction can effectively proceed under natural sunlight irradiation. In addition, this reaction can be easily extended to a gram-scale level, and its generality is ascertained by asymmetric α-benzylation reactions on various substituted aldehydes and alkyl bromides.
醛的催化不对称α-苄基化反应是有机合成中极具价值的反应。例如，生成的α-杂芳基甲基醛，如()-2-甲基-3-(吡啶-4-基)丙醛(()-MPP)，是一类重要的合成子，可用于制备生物活性药物和天然产物。本文报道了一种新的简便合成方法，使用多功能手性共价框架(CCOF)催化剂，以非均相方式实现醛与空间位阻较小的卤代烃之间的不对称分子间α-苄基化反应。将手性联萘酚磷酸和Cu(ii)-卟啉模块整合到单一的COF框架中，使所得的()-CuTAPBP-COF具有同时存在的布朗斯特和路易斯酸性位点、坚固的手性限制空间以及可见光诱导的光热转换特性。这些特性使其能够通过可见光诱导的光热转换高效促进醛的分子间不对称α-苄基化反应。值得注意的是，这种光诱导热驱动反应在自然阳光照射下能够有效进行。此外，该反应可以很容易地扩大到克级规模，并且通过对各种取代醛和烷基溴进行不对称α-苄基化反应确定了其通用性。
