Highly enantioselective synthesis of atropisomeric anilide derivatives through catalytic asymmetric N-arylation: conformational analysis and application to asymmetric enolate chemistry.
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).
Kitagawa
Osamu
O
Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. kitagawa@ps.toyaku.ac.jp
Yoshikawa
Masatoshi
M
Tanabe
Hajime
H
Morita
Tomofumi
T
Takahashi
Masashi
M
Dobashi
Yasuo
Y
Taguchi
Takeo
T
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
D000813:Anilides; D009578:Nitrobenzenes; D010165:Palladium