Computational Insights into the Divergent Regioselectivities for Nickel‐Catalyzed Dicarbofunctionalization of Allyl Moiety of N‐Allyl‐2‐aminopyrimidine

Abstract

Herein, the origins of organohalide-dependent regioselectivities for Ni-catalyzed dicarbofunctionalization of allyl moiety of N-allyl-2-aminopyrimidine were explored by computational studies. When aryl iodides are used for the dicarbofunctionalization, the detailed reaction mechanistic pathway follows the sequential oxidative addition (OA), migratory insertion (MI), β-H elimination, H-migration, transmetalation, and reductive elimination (RE) to afford the 1,3dicarbofunctionalization products. Due to the presence of chelation of the pyrimidinyl moiety of substrate with Ni, the competitive β-H elimination leading to the product of Heck reaction is less favourable and thus the regioselective β-H elimination occurs. The formation of thermodynamically more stable intermediate is the driving force for the subsequent H-migration. When alkenyl bromides are used, alternative regioselectivity to give 1,2-dicarbofunctionalization products is obtained and the proposed mechanistic pathway proceeds sequentially via OA, MI, transmetalation, and RE. The main reason accounting for the different regioselectivity between aryl iodides and alkenyl bromides involved in dicarbofunctionalization is revealed. In addition, the reversed 2,1-regioselectivity achieved by using alkynyl halides in the Ni-catalyzed dicarbofunctionalization is via sequential steps of OA, transmetalation, MI, and RE. The mechanistic difference that the migratory insertion step is unlikely to occur after OA, which is in contrast to the other two mechanistic pathways, is rationalized.

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

“…Subsequently, the Gibbs free energy profile for the oxidative addition steps involved in the C−O bond activation process was presented in Figure 15 [70] . Ni(PEt 3 ) 4 was initially coordinated to IM27 , and depending on the orientation of the allylic ligand and PEt 3 on Cu catalysts, isomers IM28 or IM30 could be formed through ligand substitution.…”

“…Subsequently, the Gibbs free energy profile for the oxidative addition steps involved in the CÀ O bond activation process was presented in Figure 15. [70] Ni(PEt 3 ) 4 was initially coordinated to IM27, and depending on the orientation of the allylic ligand and PEt 3 on Cu catalysts, isomers IM28 or IM30 could be formed through ligand substitution. Oxidative addition then occurred, producing intermediates IM29 and IM31 via transition states TS11 and TS12 with free energy barriers of 23.9 and 28.1 kcal/mol, respectively.…”