Premium
A Predictive Model Towards Site‐Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl⋅LiCl
Author(s) -
Balkenhohl Moritz,
Jangra Harish,
Makarov Ilya S.,
Yang ShuMei,
Zipse Hendrik,
Knochel Paul
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202005372
Subject(s) - deprotonation , metalation , chemistry , regioselectivity , computational chemistry , organic chemistry , catalysis , ion
The development of a predictive model towards site‐selective deprotometalation reactions using TMPZnCl⋅LiCl is reported (TMP=2,2,6,6‐tetramethylpiperidinyl). The p K a values of functionalized N ‐, S ‐, and O ‐heterocycles, arenes, alkenes, or alkanes were calculated and compared to the experimental deprotonation sites. Large overlap (>80 %) between the calculated and empirical deprotonation sites was observed, showing that thermodynamic factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Additionally, various new N ‐heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model.