title: Highly enantioselective synthesis of atropisomeric anilide derivatives through catalytic asymmetric N-arylation: conformational analysis and application to asymmetric enolate chemistry.
abstract: In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)(2) catalyst, N-arylation (aromatic amination) of various o-tert-butylanilides with p-iodonitrobenzene proceeds with high enantioselectivity (88-96% ee) to give atropisomeric N-(p-nitrophenyl)anilides having an N-C chiral axis in good yields. Atropisomeric anilide products highly prefer to exist as the E-rotamer which has trans-disposed o-tert-butylphenyl group and carbonyl oxygen. The application of the present catalytic enantioselective N-arylation to an intramolecular version gives atropisomeric lactam derivatives with high optical purity (92-98% ee). The reaction of the lithium enolate prepared from the atropisomeric anilide and lactam products with various alkyl halides gives alpha-alkylated products with high diastereoselectivity (diastereomer ratio = 13:1 to 46:1).
authors.affiliation: Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. kitagawa@ps.toyaku.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Kitagawa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Tanabe
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Morita
authors.forename: Masashi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Dobashi
authors.forename: Takeo
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000586:Amination; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D009578:Nitrobenzenes / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000813:Anilides; D009578:Nitrobenzenes; D010165:Palladium