N- versus O-Arylation of Aminoalcohols: Orthogonal Selectivity in Copper-Based Catalysts
“N- versus O-Arylation of Aminoalcohols: Orthogonal Selectivity in Copper-Based Catalysts”, J. Am. Chem. Soc., 2007, 129(12), 3490-3491.
Two complementary protocols for copper-catalyzed arylation of aminoalcohols were developed. Selective N-arylation was accomplished at room temperature using 2-isobutyrylcyclohexanone (a beta-diketone) as supporting ligand, while selective O-arylation required the use of 3,4,7,8-tetramethylphenanthroline at 80-110 degrees C. Systematic examination of the reaction scope revealed that high levels of selectivity are achieved for a variety of substrates, provided that nonchelating (or weakly chelating) aminoalcohols are used. The generality of the method was highlighted by the synthesis, in a pairwise fashion, of a number of functionalized N- and O-arylated aminoalcohols.