Mechanistic investigations on asymmetric N-H insertion of amines catalyzed by palladium-chiral guanidine complex

作者：Li, Jing; Su, Zhishan^*; Wang, Junming; Hu, Changwei

来源：Journal of Catalysis, 2018, 364: 426-436.

DOI：10.1016/j.jcat.2018.06.005

• Asymmetric catalysis
• Palladium
• Chiral guanidine
• Insertion reaction
• OFT calculation

The mechanism and stereoselectivity of the asymmetric N-H insertion reactions between alpha-diazocarbonyl compounds and amines mediated by palladium-chiral guanidine complexes were investigated at the BP86-D3(BJ)/def2TZVP (SMD, CH2Cl2)//BP86-D3(BJ)/def2SVP (SMD, CH2Cl2) level at 303 K. The non-catalytic reaction occurred through a stepwise mechanism, with a high activation barrier of 56.4 kcal mol(-1). Good linear correlations between the global nucleophilicity index (N) of amine, Hammett substituent constants (sigma(p)), and the activation energy barriers (Delta G(not equal)) were found. The Pd(0)-guanidinecat-alyzed reaction consisted of three continuous steps, including: (i) generation of Pd-carbene intermediate by dinitrogen loss from alpha-diazoesters substrate, (ii) formation of C-N bond, and (iii) 1,2-H transfer by metal-associated ylide, accompanying with the regeneration of catalyst. A water molecule accelerated the final H-transfer by constructing hydrogen bonding network. The cyclohexyl group in ligand provided sufficient steric shielding around Pd-carbene intermediate from the re-face attack by amines. The combination of the hydrogen bonding orientation of amide moiety of guanidine ligand, as well as the steric repulsion between the ester group of alpha-diazoester substrate and bulky -CH(Ph)(2) group in ligand played an important role in controlling the stereoselectivity, affording the predominant S-configuration product observed in experiment. Introducing one aromatic ring to chiral backbone of the guanidine ligand enhanced the enantiodifferentiation of products by increasing the difference of strain energy (Delta Delta E-strain) of Pd-carbene moiety along two competing pathways. Different fromPd(0)-catalyst, the Pd (II)-chiral guanidine complex accelerated N-H insertion reaction via Lewis acid catalysis. In this process, the formation of free ylide in the reaction led to low ee. These results were in good agreement with experimental observations.

• 出版日期2018-8
• 单位四川大学