Synthesis of Phenanthrenes and Polycyclic Heteroarenes by Transition‐Metal Catalyzed Cycloisomerization Reactions

Abstract

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.

Synthesis of 3-methoxy-6-phenyl-6, 6a-dihydro-[1] benzopyrano- [3, 4-b] [1] benzopyran.

“…When PtCl 2 is used instead of PtCl 4 , the yield decreases (29%). This result is conform to others described in the literature [23]. Howover, Federov and al showed that the intramolecular hydroarylation can be obtained in higher yield (60-91%) using catalytic amount of Pd(OAc) 2 [24].…”

1,3-Dien-5-ynes: Versatile Building Blocks for the Synthesis of Carbo- and Heterocycles

“…3). 26,123 The authors also propose a vinylidene intermediate for this transformation, which was initially supported by a teorethical analysis. 28 Nevertheless, later computational studies have demonstrated that a mechanism consisting in a 6-endo cyclization followed by consecutive 1,2-H/1,2-halo migrations cannot be ruled out.…”

Formation of C(sp2)Boronate Esters by Borylative Cyclization of Alkynes Using BCl3

“…Thed isparity in reaction outcome between BCl 3 (borylative cyclization) and GaCl 3 (cycloisomerization) is again noteworthy. [22] Theb orylative cyclization of 2-alkynyl-1,1'-biphenyls forms versatile intermediates (e.g., 6)w hich can be transformed into desirable materials,s uch as dibenzochrysenes by established methodologies. [23] Them ore functionality-rich precursor 7, containing ah eteroaromatic, ab romide,a nd ah exyl-substituted alkyne,was also amenable to borylative cyclization and delivered 8 in 58 %y ield.…”