02021nas a2200217   4500008004100000022001400041245011000055210006900165260000800234490000700242520126500249653001901514653001201533653001401545653001901559653002601578100002601604700002401630700002001654856012901674       2025                        eng d  a1867-388000aPalladium-catalyzed regioselective C(4)-H fluoroalkoxylation of indoles through weak chelation assistance0 aPalladiumcatalyzed regioselective C4H fluoroalkoxylation of indo  cJAN0 v173 a<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>
10aC-H activation10aindoles10aPalladium10aRegioselective10aTrifluoroalkoxylation1 aVijaykumar, Muniyappa1 aGonnade, Rajesh, G.1 aPunji, Benudhar  uhttps://library.ncl.res.in/content/palladium-catalyzed-regioselective-c4-h-fluoroalkoxylation-indoles-through-weak-chelation