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Pd II ‐Catalyzed Conjugate Addition of Boronic Acids to Ketoglutaconic Esters toward the Synthesis of Functionalized Pyridazin‐3(2 H )‐ones with Neuroprotective Activity
Author(s) -
Roscales Silvia,
Ortega Andrea,
MartínAragón Sagrario,
BermejoBescós Paloma,
Csákÿ Aurelio G.
Publication year - 2012
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.201200734
Subject(s) - chemistry , conjugate , catalysis , regioselectivity , aryl , combinatorial chemistry , organic chemistry , alkyl , mathematics , mathematical analysis
The development of the regioselective conjugate addition of boronic acids to ketoglutaconic esters under transition metal catalysis is reported. Among the different catalysts tested for this transformation, the dicationic Pd II catalysts generated with Pd(OCOCF 3 ) 2 , dppben, and HBF 4 performed best in terms of yields, regioselectivities and avoidance of Heck‐type by‐products. The resulting 4‐aryl‐2‐oxopentadienoates were transformed into pyridazin‐3(2 H )‐ones, potentially useful for the therapy of neurodegenerative diseases. These compounds simultaneously exhibited β‐secretase activity, inhibition of β‐amyloid (βA) aggregation, and disaggregation of pre‐formed βA fibrils, and also had a good scavenging profile for intracellular reactive oxygen species (ROS).