@article {49411,
	title = {Palladium-catalyzed regioselective C(4)-H fluoroalkoxylation of indoles through weak chelation assistance},
	journal = {ChemCatChem},
	year = {2024},
	month = {OCT},
	type = {Article; Early Access},
	abstract = {<p>
	Installing fluoroalkyl motifs into biorelevant indoles is particularly interesting due to their ubiquitous presence in drug molecules. Herein, we demonstrate the regioselective C4 fluoroalkoxylation of indoles using fluoroalcohols via palladium-catalyzed chelation-assisted C \&amp; horbar;H activation. The weak chelating benzoyl moiety at the C3 position acts as a directing group for remote C(4)\&amp; horbar;H fluoroalkoxylation of diversely substituted indoles. This methodology demonstrates a high level of regioselectivity and tolerates a range of crucial functional groups, yielding diverse trifluoroalkoxylated indoles in moderate to good yields. Removal of directing/protecting groups and further functionalization established the synthetic utility of the methodology. A preliminary mechanistic investigation is conducted by isolating the palladacycle intermediate and performing the deuterium scrambling study. The regioselective C4 fluoroalkoxylation of indoles with various fluoroalcohols is achieved by the palladium-catalyzed weak chelation assistance strategy. The reaction is compatible for a range of important functionalities and proceeds via the intermediacy of a six-membered palladacycle following a Pd(II)/Pd(IV) pathway. image</p>
},
	keywords = {C-H activation, indoles, Palladium, Regioselective, Trifluoroalkoxylation},
	issn = {1867-3880},
	doi = {10.1002/cctc.202401188},
	author = {Vijaykumar, Muniyappa and Gonnade, Rajesh G. and Punji, Benudhar}
}
