Organic Chemistry, Contributed Talk (15min)
OC-025

Palladium(0)-Catalyzed Enantioselective C(sp2)–H Arylation of (Hetero)arenes

S. Guo1, S. Huh1, O. Baudoin1*
1University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056 Basel

Atropisomeric (hetero)biaryls are motifs with increasing significance in asymmetric catalysis and natural products.1,2 The straightforward construction of the stereogenic axis by efficient C–H functionalization methods is rare and challenging.3 An intermolecular and highly enantioselective C–H arylation of relevant heteroarenes providing an efficient access to atropisomeric (hetero)biaryls is reported.4 The use of a Pd(0) complex equipped with H8-BINAPO as chiral ligand enables the direct functionalization of a broad range of 1,2,3-triazoles and pyrazoles in excellent yields and selectivities of up to 97.5:2.5 er. The method also allows for an atroposelective double C–H arylation for the construction of two stereogenic axes with >99.5:0.5 er.

Enantiopure carbohelicenes are important target molecules in molecular recognition and material science due to their strong circularly polarized luminescence (CPL) properties.5,6 However, a general enantioselective process for the construction of lower, nonfused low-order carbo[n]helicenes (n = 4-6) is still lacking.7 Herein, we report that Pd-catalysed enantioselective C–H arylation provides a simple and general access to these carbo[n]helicenes.8 Computational studies revealed a complex enantio-induction process. A systematic study of the CPL properties of the synthesised carbo[n]helicenes, showed that carbo[4]helicenes display comparable CPL responses to the higher carbo[6]helicenes. This suggests new avenues for the optimisation of chiroptical properties of helicene systems.


[1] Mariette M. Pereira, Mário J. F. Calvete, Rui M. B. Carrilho, Artur R. Abreu, Chem. Soc. Rev. 2013, 42, 6990-7027.
[2] Gerhard Bringmann, Tanja Gulder, Tobias A. M. Gulder, Matthias Breuning, Chem. Rev. 2011, 111, 563–639.
[3] Gang Liao, Tao Zhou, Qi-Jun Yao, Bing-Feng Shi, Chem. Commun. 2019, 55, 8514-8523.
[4] In collaboration with the Cramer group, EPFL: Qui-Hien Nguyen,+ Shu-Min Guo,+ Titouan Royal, Olivier Baudoin, Nicolai Cramer, J. Am. Chem. Soc. 2020, 142, 2161−2167.
[5] Marc Gingras, Chem. Soc. Rev. 2013, 42, 1051–1095.
[6] Wen-Long Zhao, Meng Li, Hai-Yan Lu, Chuan-Feng Chen, Chem. Commun. 2019, 55, 13793–13803.
[7] Yun Shen, Chuan-Feng Chen, Chem. Rev. 2012, 112, 1463–1535.
[8] Shu-Min Guo, Soohee Huh, Max Coehlo, Li Shen, Grégory Pieters, Olivier Baudoin, Submitted work. DOI: 10.26434/chemrxiv-2022-gvp7b.