Exploring the Mechanism of the Palladium-Catalyzed 3-Butene-2-ol Amination Reaction: A DFT Study

Abstract

Palladium-catalyzed asymmetric allylic substitution, due to its valuable reactive profile, has become a quite useful tool in organic synthesis fields. In the present study, density functional theory (DFT) calculations were applied to investigate the important factors for palladium-catalyzed 3-butene-2-ol and methylaniline amination reaction, with tetrahydrofuran (THF) as solvent. We find that this catalytic protocol results in high regio-and stereoselectivity, which is in line with the experimental result. According to our calculations, the high regio-and stereoselectivity is caused by the steric hindrance between the substrate and the catalyst ligand. To verify this point, we further explore the reactive process with different axial chirality on the catalyst ligand (altering the steric hindrance), and the results suggest that the preponderant R chiral configuration product has reversed. These results could lead to a better understanding of the mechanism for 3-butene-2-ol amination reaction and are helpful for the design of the corresponding catalyst ligand in the industry.

Recent DFT Calculations on the Mechanism of Transition‐Metal‐Catalyzed C−O Activation of Alcohols

“…[76] In 2020, Huang and co-workers utilized DFT calculations to investigate the mechanism underlying the palladium-catalysed amination of 3-buten-2-ol and methylaniline, providing insights into the critical factors affecting this reaction (Figure 24). [77] It was found that ammonium A obtained through the reaction between methylaniline and allylicpalladium species plays a crucial role in CÀ O bond activation of allyl alcohol. Meanwhile, steric hindrance between the substrate and the ligands on the catalyst is responsible for regioselectivity and stereoselectivity.…”

Racemic Benzenesulfonohydrazide Enantioconvergent Tertiary C(sp3)−H Amination Catalyzed by Copper and Chiral Phosphoric Acid: Mechanistic Insights and Computational Prediction

“…In addition to the above experimental work, some theoretical studies on the mechanisms of chiral amine synthesis have also been reported [25–28] . Zheng and co‐workers [26] studied Ir catalyzed α‐amidation of 2‐acylimidazoles and demonstrated a significant effect of nitrene insertion.…”

“…Sunoj et al [27] investigated the mechanistic insights into asymmetric amination of diazoacetate catalyzed by dirhodium tetra(trifluoro)acetate with chiral SPINOL-phosphoric acid and found a stereo-controlling transition state with cooperative participation of both catalysts. Huang and Liu [28] explored a palladium-catalyzed 3-butene-2-ol and methyl aniline amination reaction and found that the high regio-and stereoselectivity is caused by the steric hindrance between the substrate and the catalyst ligand.…”

“…[23,24] In addition to the above experimental work, some theoretical studies on the mechanisms of chiral amine synthesis have also been reported. [25][26][27][28] Zheng and co-workers [26] studied Ir catalyzed α-amidation of 2-acylimidazoles and demonstrated a significant effect of nitrene insertion. Sunoj et al [27] investigated the mechanistic insights into asymmetric amination of diazoacetate catalyzed by dirhodium tetra(trifluoro)acetate with chiral SPINOL-phosphoric acid and found a stereo-controlling transition state with cooperative participation of both catalysts.…”