Modulating reactivity and diverting selectivity in palladium-catalyzed heteroaromatic direct arylation through the use of a chloride activating/blocking group.
Through the introduction of an aryl chloride substituent, the selectivity of palladium-catalyzed direct arylation may be diverted to provide alternative regioisomeric products in high yields. In cases where low reactivity is typically observed, the presence of the carbon-chlorine bond can serve to enhance reactivity and provide superior outcomes. From a strategic perspective, the C-Cl bond is easily introduced and can be employed in a variety of subsequent transformations to provide a wealth of highly functionalized heterocycles with minimal substrate preactivation. The impact of the C-Cl functional group on direct arylation reactivity has also been evaluated mechanistically, and the observed reactivity profiles correlate very well with that predicted by a concerted metalation-deprotonation pathway.
Liégault
Benoît
B
Centre for Catalysis Research & Innovation, Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada. bliegaul@uottawa.ca
Petrov
Ivan
I
Gorelsky
Serge I
SI
Fagnou
Keith
K
D002384:Catalysis; D002712:Chlorides / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D002712:Chlorides; D003432:Cross-Linking Reagents; D006571:Heterocyclic Compounds; D010165:Palladium