Ye Young Sebastian, Laverny Aragorn, Wodrich Matthew D, Laplaza Ruben, Fadaei-Tirani Farzaneh, Scopelliti Rosario, Corminboeuf Clemence, Cramer Nicolai
Laboratory of Asymmetric Catalysis and Synthesis, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Laboratory for Computational Molecular Design, Institute of Chemical Sciences and Engineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
J Am Chem Soc. 2024 Dec 18;146(50):34786-34795. doi: 10.1021/jacs.4c13279. Epub 2024 Dec 6.
Chiral cyclopentadienyl (Cp) metal complexes are frequently used in asymmetric catalysis by virtue of their high reactivity and selectivity. Planar-chiral-only rhodium and iridium cyclopentadienyl complexes are particularly promising due to unrestricted chemical space for Cp ligand design while retaining structural simplicity. However, they are currently still niche because of a lack of efficient synthetic strategies that avoid lengthy chiral auxiliary routes or chiral preparatory HPLC resolution of the complexes. To streamline access to such planar-chiral-only Cp-metal complexes, we designed a straightforward, highly enantiospecific, point-to-planar chirality transfer complexation via facially selective concerted-metalation-deprotonation between metal-carboxylate precursor [M(olefin)OAc] and a chiral cyclopentadiene. This entirely avoids the typical stereoablative complexation of an achiral cyclopentadienyl anion that detrimentally yields a racemate. Exploiting the described enantiospecific complexation protocol and a simple divergent synthetic route to suitable chiral cyclopentadienes, we generated a structurally diverse library of new planar chiral Cp-Rh(I), Cp-Ir(I), Cp-Rh(III), and Cp-Ir(III) complexes. Moreover, the enantiospecific complexation step can be concatenated with a preceding Au-catalyzed cyclization in an efficient one-pot process that likely involves an elaborate point-to-axial-to-point-to-planar chirality transfer. Guided by computational selectivity predictions, the structure of a Cp-Rh complex in our library was tuned to optimize reactivity and selectivity in the asymmetric C-H functionalization of a benzamide with various challenging alkenes. With an optimized Cp-Rh complex in hand, we showcased its excellent catalytic performance and high selectivity for refractory alkene substrates that reacted in poor selectivity with previous Cp-Rh catalysts.
手性环戊二烯基（Cp）金属配合物因其高反应活性和选择性而常用于不对称催化。仅具有平面手性的铑和铱环戊二烯基配合物特别有前景，因为Cp配体设计的化学空间不受限制，同时保持结构简单。然而，由于缺乏有效的合成策略来避免冗长的手性辅助路线或配合物的手性制备HPLC拆分，它们目前仍然处于小众地位。为了简化对这种仅具有平面手性的Cp-金属配合物的获取，我们设计了一种直接、高度对映体特异性的点到平面手性转移络合反应，通过金属羧酸盐前体[M(烯烃)OAc]与手性环戊二烯之间的面选择性协同金属化-去质子化反应实现。这完全避免了非手性环戊二烯基阴离子的典型立体消融络合反应，该反应会不利地产生外消旋体。利用所描述的对映体特异性络合方案和一条简单的合成不同手性环戊二烯的发散合成路线，我们生成了一个结构多样的新型平面手性Cp-Rh(I)、Cp-Ir(I)、Cp-Rh(III)和Cp-Ir(III)配合物库。此外，对映体特异性络合步骤可以与之前的金催化环化反应在一个高效的一锅法过程中串联起来，该过程可能涉及复杂的点到轴到点到平面的手性转移。在计算选择性预测的指导下，我们库中一种Cp-Rh配合物的结构被调整，以优化其在苯甲酰胺与各种具有挑战性的烯烃的不对称C-H官能化反应中的反应活性和选择性。有了优化后的Cp-Rh配合物，我们展示了其优异的催化性能以及对难反应烯烃底物的高选择性，而这些底物与之前的Cp-Rh催化剂反应时选择性较差。
