Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling

We
report the development of a new class of guanidine-containing
peptides as multifunctional ligands for transition-metal catalysis
and its application in the remote desymmetrization of diarylmethanes
via copper-catalyzed Ullman cross-coupling. Through design of these
peptides, high levels of enantioinduction and good isolated yields
were achieved in the long-range asymmetric cross-coupling (up to 93:7
er and 76% yield) between aryl bromides and malonates. Our mechanistic
studies suggest that distal stereocontrol is achieved through a Cs-bridged
interaction between the Lewis-basic C-terminal carboxylate
of the peptides with the distal arene of the substrate.