Synthesis of Indole Oligomers Via Iterative Suzuki Couplings Jason M. Belitsky Department of Chemistry and Biochemistry, Oberlin College, Oberlin OH, 44074 H N
Br
HCl THF/H2O 2 mol % Pd2(dba)3 4 mol % XPhos K3PO4, 10 % aq. dioxane 80 ºC, overnight
3 steps from commercially available 4-Br-indole
N H
2 mol % Pd2(dba)3 4 mol % XPhos K3PO4, 10 % aq. dioxane 80 ºC, overnight
N H
N H
54 %
H N
Pd(OAc)2 (5 mol %) TsCl (50 mol %) Na2CO3, H2O/acetone, room temp, 2 hrs N H
81 %
53 % yield (2 steps)
Eumelanin, the black to brown human pigment, is composed of oligomers of dihydroxyindoles. In order to study this fascinating biomaterial, we are developing synthetic methods for the construction of (dihydroxy)indole oligomers. We recently completed an iterative synthesis of an indole trimer (shown above) featuring Suginome’s B-dan protecting group and optimized Suzuki cross-coupling conditions. In the course of this work, we serendipitously found and then optimized conditions for Suzuki homocoupling of indole boronic acids (left).
