title: Enantioselective synthesis of atropisomeric benzamides through peptide-catalyzed bromination.
abstract: We report the enantioselective synthesis of atropisomeric benzamides employing catalytic electrophilic aromatic substitution reactions involving bromination. The catalyst is a simple tetrapeptide bearing a tertiary amine that may function as a Brønsted base. A series of tri- and dibrominations were accomplished for a range of compounds bearing differential substitution patterns. Tertiary benzamides represent appropriate substrates for the reaction since they exhibit sufficiently high barriers to racemization after ortho functionalization. Mechanism-driven experiments provided some insight into the basis for selectivity. Examination of the observed products at low conversion suggested that the initial catalytic bromination may be regioselective and stereochemistry-determining. A complex between the catalyst and substrate was observed by NMR spectroscopy, revealing a specific association. Finally, the products of these reactions may be subjected to regioselective metal-halogen exchange and trapping with I(2), setting the stage for utility.
authors: Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520-8107, USA.
authors: Kimberly T
authors: KT
authors: Barrett
authors: Scott J
authors: SJ
authors: Miller
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis*; D001966:Bromine / Q000737:chemistry*; D002384:Catalysis; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001549:Benzamides; D010455:Peptides; D001966:Bromine