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Mechanism of Copper(I)‐Catalyzed Allylic Alkylation of Phosphorothioate Esters: Influence of the Leaving Group on α Regioselectivity
Author(s) -
Sheng Wenhao,
Wang Mian,
Lein Matthias,
Jiang Linbin,
Wei Wanxing,
Wang Jianyi
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201300202
Subject(s) - regioselectivity , allylic rearrangement , chemistry , isomerization , leaving group , catalysis , medicinal chemistry , transition state , alkylation , tsuji–trost reaction , stereochemistry , organic chemistry
The mechanism of Cu I ‐catalyzed allylic alkylation and the influence of the leaving groups (OPiv, SPiv, Cl, SPO(O i Pr) 2 ; Piv: pivavloyl) on the regioselectivity of the reaction have been explored by using density functional theory (DFT). A comprehensive comparison of many possible reaction pathways shows that [( i Pr) 2 Cu] − prefers to bind first oxidatively to the double bond of the allylic substrate at the anti position with respect to the leaving group, and this is followed by dissociation of the leaving group. If the leaving group is not taken into account, the reaction then undergoes an isomerization and a reductive elimination process to give the α‐ or γ‐selective product. If OPiv, SPiv, Cl, or SPO(O i Pr) 2 groups are present, the optimal route for the formation of both α‐ and γ‐substituted products changes from the stepwise elimination to the direct process, in which the leaving group plays a stabilizing role for the reactant and destabilizes the transition state. The differences to the energy barrier for the α‐ and γ‐substituted products are 2.75 kcal mol −1 with SPO(O i Pr) 2 , 2.44 kcal mol −1 with SPiv, 2.33 kcal mol −1 with OPiv, and 1.98 kcal mol −1 with Cl, respectively; these values show that α regioselectivity in the allylic alkylation follows a SPO(O i Pr) 2 >SPiv>OPiv>Cl trend, which is in satisfactory agreement with the experimental findings. This trend mainly originates in the differences between the attractive electrostatic forces and the repelling steric interactions of the SPO(O i Pr) 2 , SPiv, OPiv, and Cl groups on the Cu group.