Premium
Substituent Effects on Oxidation‐Induced Formation of Quinone Methides from Arylboronic Ester Precursors
Author(s) -
Cao Sheng,
Christiansen Robin,
Peng Xiaohua
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.201300539
Subject(s) - chemistry , substituent , reactivity (psychology) , quinone methide , quinone , leaving group , medicinal chemistry , phenols , ether , polar effect , phenol , hammett equation , organic chemistry , catalysis , kinetics , reaction rate constant , medicine , physics , alternative medicine , pathology , quantum mechanics
A series of arylboronic esters containing different aromatic substituents and various benzylic leaving groups (Br or N + Me 3 Br − ) have been synthesized. The substituent effects on their reactivity with H 2 O 2 and formation of quinone methide (QM) have been investigated. NMR spectroscopy and ethyl vinyl ether (EVE) trapping experiments were used to determine the reaction mechanism and QM formation, respectively. QMs were not generated during oxidative cleavage of the boronic esters but by subsequent transformation of the phenol products under physiological conditions. The oxidative deboronation is facilitated by electron‐withdrawing substituents, such as aromatic F, NO 2 , or benzylic N + Me 3 Br − , whereas electron‐donating substituents or a better leaving group favor QM generation. Compounds containing an aromatic CH 3 or OMe group, or a good leaving group (Br), efficiently generate QMs under physiological conditions. Finally, a quantitative relationship between the structure and activity has been established for the arylboronic esters by using a Hammett plot. The reactivity of the arylboronic acids/esters and the inhibition or facilitation of QM formation can now be predictably adjusted. This adjustment is important as some applications may benefit and others may be limited by QM generation.