In the past decade, iridium-catalyzed asymmetric allylic substitution reactions have developed into a highly efficient method for the construction of carbon–carbon and carbon–heteroatom bonds. The chiral branched allylic products can be obtained with high yields and enantioselectivity using monosubstituted allylic carbonates as the substrates. Feringa-type phosphoramidites are the most frequently employed chiral ligands for this transformation. However, the substrate scope is still limited, for instance the “ortho-unfavorable effect”. The yields and ees of the products will be significantly lower when the ortho-substituted cinnamyl carbonates are subjected to the Ir/phosphoramidite system.

 

Iridium/L1-Catalyzed Asymmetric Allylic Substitution Reactions (Image by YOU Shuli@ SIOC)

　  In 2009, the researchers from the State Kay Laboratory of Organometallic Chemistry developed a novel 2-methyltetrahydroquinoline-based N-aryl phosphoramidite ligand (L1) that can overcome the “ortho-unfavorable effect”. The ortho-substituted cinnamyl carbonates could be well tolerated in the asymmetric allylic alkylation reactions of indoles ( Synthesis 2009, 2076-2082.). In addition, this new ligand was also found highly efficient in the iridium-catalyzed asymmetric allylic dearomatization reactions of indoles and pyrroles, allowing facile access to the chiral spirocyclic skeletons that are widely distributed in natural products as well as molecules of pharmaceutical interests ( J. Am. Chem. Soc. 2010, 132, 11418-11419., Chem. Sci.2012,3, 205-208.).

　  Recently, assisted by both computational and experimental methods, the researchers disclosed that the active catalytic species of the Ir/L1 system is the iridacyclic complex generated through the C(sp2)–H bond activation at C8-position of the quinoline ring. The relatively larger chiral pocket makes the chiral discrimination possible for the steric hindered ortho-substituted cinnamyl carbonates. Further studies revealed that the enantioselectivity in this reaction is not originated from the facial-selectivity of the nucleophilic attack, but determined by the rate difference between the formations of the endo or exo π-allyliridium complexes. This work has been published in the Journal of the American Chemical Society as an Article ( J. Am. Chem. Soc.2012,134, 4812-4821.).

　  This project was supported by the National Natural Science Foundation of China, the Ministry of Science and Technology (973 Program), and the Chinese Academy of Sciences.