State Key Laboratory of Synthetic Chemistry and Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong 999077, China.
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Changchun 130023, China.
J Am Chem Soc. 2022 Aug 17;144(32):14864-14873. doi: 10.1021/jacs.2c06240. Epub 2022 Aug 3.
Biaryl phosphines bearing C-C axial chirality are commonly known and have been successfully applied in many asymmetric catalyses. Nevertheless, the development of a chiral ligand having an axially chiral C-N backbone remains elusive due to its undesirable less restricted rotational barrier. In fact, it is highly attractive to overcome this challenge in ligand development as the incorporation of an N-donor component at the chiral axis is more favorable toward the transient metal coordination, and thus, a better outcome of stereocommunication is anticipated to the approaching substrates. Herein, we present a rational design of a new collection of chiral phosphines featuring a C-N axial chirality and their applications in enantioselective Suzuki-Miyaura cross-coupling for accessing highly steric hindered tetra--substituted biaryls (26 examples up to 98:2 er). It is worth noting that the embodied carbazolyl framework is crucial to succeed the reaction, by the fruitful steric relief of bulky substrate coordination and transmetalation via a fleeting Pd-N jumping to Pd-π fashion. DFT calculation reveals an interesting Pd-arene-walking characteristic across the carbazolyl plane for attaining a lower energy-preferred route in a catalytic cycle. The theoretical study successfully predicts the stereooutcome and matches the enantioselectivity with the experimental results.
具有 C-C 轴手性的双芳基膦是众所周知的，并且已成功应用于许多不对称催化反应中。然而，由于其不理想的旋转位垒限制较小，具有轴手性 C-N 骨架的手性配体的开发仍然难以捉摸。事实上，克服配体开发中的这一挑战具有很高的吸引力，因为在手性轴上引入 N-给体部分更有利于瞬态金属配位，因此，预期对接近的底物的立体通讯会有更好的结果。在此，我们提出了一系列具有 C-N 轴手性的新型手性膦的合理设计及其在手性Suzuki-Miyaura 交叉偶联反应中的应用，以获得高度空间位阻的四取代联芳基（26 个实例，对映选择性高达 98:2 er）。值得注意的是，所体现的咔唑骨架对于反应的成功至关重要，通过庞大的底物配位和通过瞬间 Pd-N 跳跃到 Pd-π 方式进行的转金属化来实现有效的空间位阻缓解。DFT 计算揭示了在催化循环中，Pd-芳基在咔唑平面上的有趣的“行走”特征，以达到较低能量优先途径。该理论研究成功地预测了立体结果，并与实验结果相匹配。
