DFT study of Ni-catalyzed intramolecular asymmetric anti-hydrometalative cyclization of alkynone: mechanism and origins of selectivity

Li，Jinxia1; Tang，Dingyi1; Zhang，Yu1; Chen，Weichi1; Su，Xiaoxi1; Yu，Peiyuan2; Qu，Shuanglin1

2023-07-18

10.1039/d3qo00701d

Organic Chemistry Frontiers   影响因子和分区

2052-4110

2052-4129

The intramolecular cyclization of alkynones catalyzed by Ni catalysts has attracted much attention due to its versatile application in the synthesis of cyclic compounds. Herein, we present a comprehensive investigation into the mechanism and origins of selectivities of this reaction using density functional theory (DFT) computations. The Ni(0) catalyst system selectively forms 5-exocyclic products while the Ni(ii) catalyst system generates 6-endocyclic or 5-exocyclic products because they follow different mechanisms. The Ni(0) system follows an oxidative cyclometalation, hydride transfer, and reductive elimination pathway. However, in the Ni(ii) system, the reaction starts with the alkyne insertion followed by cis/trans isomerization, carbonyl insertion, hydrolysis, and catalyst regeneration, among which the alkyne insertion determines the regioselectivity and the carbonyl insertion determines the enantioselectivity. In particular, the C = C bond of the Ph-alkynone substrate prefers 1,2-insertion due to the conjugation effect, while the C C bond of the Bu-alkynone substrate favors 2,1-insertion owing to the electron-donating property of the Bu group. It is notable that a cis/trans isomerization process is necessary for the formation of the 6-endocyclic product but not for the formation of the 5-endocyclic product. The rationale for the (S)-enantioselectivity observed for both substrates is ascribed to favorable hydrogen bonding interactions and the less steric repulsions in the (S)-transition states of carbonyl insertion.

SCI ; EI

英语

通讯

National Natural Science Foundation of China[21903022];

Chemistry

Chemistry, Organic

WOS:001031915700001

ROYAL SOC CHEMISTRY

20233214501976

Catalysis ; Catalysts ; Cyclization ; Density functional theory ; Hydrocarbons ; Hydrogen bonds ; Isomerization ; Isomers ; Nickel compounds ; Substrates

Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Chemical Agents and Basic Industrial Chemicals:803 ; Chemical Products Generally:804 ; Organic Compounds:804.1 ; Probability Theory:922.1 ; Atomic and Molecular Physics:931.3 ; Quantum Theory; Quantum Mechanics:931.4

2-s2.0-85166743723

Scopus

1.College of Chemistry and Chemical Engineering,Hunan University,Changsha,410082,China
2.Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China

Li，Jinxia,Tang，Dingyi,Zhang，Yu,et al. DFT study of Ni-catalyzed intramolecular asymmetric anti-hydrometalative cyclization of alkynone: mechanism and origins of selectivity[J]. Organic Chemistry Frontiers,2023,10(17):4263-4274.

Li，Jinxia.,Tang，Dingyi.,Zhang，Yu.,Chen，Weichi.,Su，Xiaoxi.,...&Qu，Shuanglin.(2023).DFT study of Ni-catalyzed intramolecular asymmetric anti-hydrometalative cyclization of alkynone: mechanism and origins of selectivity.Organic Chemistry Frontiers,10(17),4263-4274.

Li，Jinxia,et al."DFT study of Ni-catalyzed intramolecular asymmetric anti-hydrometalative cyclization of alkynone: mechanism and origins of selectivity".Organic Chemistry Frontiers 10.17(2023):4263-4274.