Heteroaryl cross-coupling as an entry toward the synthesis of lavendamycin analogues: a model study.
ABC analogues of the antitumor antibiotic lavendamycin, which contain the key metal chelation site and redox-active quinone unit essential for biological activity, were prepared via the palladium(0)-catalyzed cross-coupling reaction of various 2-haloheteroaromatics with 2-stannylated pyridines and quinolines. Using the Stille reaction, 2-bromo substituted quinolines and 1-bromoisoquinolines were found to undergo efficient coupling with 2-pyridinylstannanes to provide unsymmetrical heterobiaryl derivatives. While the Stille reaction using the reverse coupling partners (i.e., 2-quinolinylstannanes and haloheteroaromatics) had not received much attention in the literature, we found that this alternative coupling reaction efficiently provided several new heterobiaryl derivatives. The gold-catalyzed intramolecular cycloisomerization of N-(prop-2-ynyl)-1H-indole-2-carboxamide smoothly afforded a beta-carbolinone derivative that was subsequently used for a Pd(0)-catalyzed cross-coupling directed toward the synthesis of lavendamycin analogues.
Verniest
Guido
G
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Gent, Belgium.
Wang
Xingpo
X
De Kimpe
Norbert
N
Padwa
Albert
A
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003432:Cross-Linking Reagents; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D013237:Stereoisomerism; D013308:Streptonigrin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D007211:Indoles; C548175:N-(prop-2-ynyl)-1H-indole-2-carboxamide; D011804:Quinolines; D013308:Streptonigrin; D010165:Palladium; C034566:lavendamycin