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Long‐Range Effects in the Metalation/Boronation of Functionalized 1,4‐Dihalobenzenes
Author(s) -
Luliński Sergiusz,
Serwatowski Janusz,
Zaczek Anna
Publication year - 2006
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200600541
Subject(s) - chemistry , lithium diisopropylamide , metalation , bifunctional , electrophile , steric effects , substituent , medicinal chemistry , carboxylate , phosphinidene , lithium (medication) , stereochemistry , organic chemistry , catalysis , medicine , ion , deprotonation , endocrinology
The lithiation/boronation of 1,4‐dihalobenzenes (Hal = F, Cl, Br) bearing various functional groups in the 2‐position was investigated using lithium diisopropylamide (LDA) as the metalating agent and trialkyl borate B(OR) 3 (R = Et, i Pr) as the electrophile. It was demonstrated that sufficient steric hindrance precludes effective ortho ‐lithiation at the 3‐position. In such cases, a strong meta ‐directing effect of an oxygen‐ or sulfur‐based substituent (OMe, OSiMe 3 , SMe), resulting in the preferred formation of 2,6‐disubstituted 1,4‐dihalobenzenes was observed. Moreover, competition experiments using 2,3‐bifunctional 1,4‐dihalobenzenes were performed to determine the relative meta ‐directing ability of carboxylate or fluorine in competition with a methoxy group. A significant buttressing effect is responsible for the course of metalation of 2‐(dimethoxymethyl)‐1,4‐dihalobenzenes (Hal = Cl, Br). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)