title: Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling.
abstract: 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.
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Byoungmoo
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Chinn
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Fandrick
authors.affiliation: Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, United States.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Senanayake
authors.affiliation: Chemical Research and Development, Pfizer Inc. , Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Singer
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520-8107, United States.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
mesh_terms: D001965:Bromides / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D003300:Copper / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008314:Malonates / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D008697:Methane / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D000072417:Protein Domains; D013237:Stereoisomerism
chemical_list: D001965:Bromides; D008024:Ligands; D008314:Malonates; D008670:Metals; D010455:Peptides; D003300:Copper; D008697:Methane