DFT Calculations Rationalize Unconventional Regioselectivity in PdII-Catalyzed Defluorinative Alkylation of gem-Difluorocyclopropanes with Hydrazones

Aili Feng; Yiying Yang; Chengbu Liu; Dongju Zhang

doi:10.1021/acs.joc.3c02770

DFT Calculations Rationalize Unconventional Regioselectivity in Pd^II-Catalyzed Defluorinative Alkylation of gem-Difluorocyclopropanes with Hydrazones

J Org Chem. 2024 May 20. doi: 10.1021/acs.joc.3c02770. Online ahead of print.

Authors

Aili Feng¹, Yiying Yang¹, Chengbu Liu¹, Dongju Zhang¹

Affiliation

¹ Key Lab of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China.

PMID: 38766868
DOI: 10.1021/acs.joc.3c02770

Abstract

Density functional theory (DFT) calculations have been conducted to gain insight into the unique formation of the branched alkylation product in the Pd^II-catalyzed defluorinative alkylation of gem-difluorocyclopropanes with hydrazones. The reaction is established to occur in sequence through oxidative addition, β-F elimination, η¹-η³ isomerization, transmetalation, η³-η¹ isomerization, 3,3'-reductive elimination, deprotonation/N₂ extrusion, and proton abstraction. The rate-determining step of the reaction is identified as the β-F elimination, featuring an energy barrier of 28.6 kcal/mol. The 3,3'-reductive elimination transition states are the regioselectivity-determining transition states. The favorable noncovalent π-π interaction between the naphthyl group of gem-difluorocyclopropane and the phenyl group of hydrazone is found to be mainly responsible for the observed regioselectivity.