Synthesis of phenanthrenes and polycyclic heteroarenes by transition-metal catalyzed cycloisomerization reactions.
Readily available biphenyl derivatives containing an alkyne unit at one of their ortho-positions are converted into substituted phenanthrenes on exposure to catalytic amounts of either PtCl2, AuCl, AuCl3, GaCl3 or InCl3 in toluene. This 6-endo-dig cyclization likely proceeds through initial pi-complexation of the alkyne unit followed by interception of the resulting eta2-metal species by the adjacent arene ring. The reaction is inherently modular, allowing for substantial structural variations and for the incorporation of substituents at any site of the phenanthrene product. Moreover, it is readily extended to the heterocyclic series as exemplified by the preparation of benzoindoles, benzocarbazoles, naphthothiophenes, as well as bridgehead nitrogen heterocycles such as pyrrolo[1,2-a]quinolines. Depending on the chosen catalyst, biaryls bearing halo-alkyne units can either be converted into the corresponding 10-halo-phenanthrenes or into the isomeric 9-halo-phenanthrenes; in the latter case, the concomitant 1,2-halide shift is best explained by assuming a metal vinylidene species as the reactive intermediate. The scope of this novel method for the preparation of polycyclic arenes is illustrated by the total synthesis of a series of polyoxygenated phenanthrenes that are close relatives of the anticancer agent combretastatin A-4, as well as by the total synthesis of the aporphine alkaloid O-methyl-dehydroisopiline and its naturally occurring symmetrical dimer.
Mamane
Victor
V
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr, Germany.
Hannen
Peter
P
Fürstner
Alois
A
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D019216:Metals, Heavy / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D010616:Phenanthrenes / Q000138:chemical synthesis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000480:Alkynes; D001713:Biphenyl Compounds; D019216:Metals, Heavy; D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons