| Palladium catalyzed cross-couplings have become a very important method of carbon-carbon bond formation. The ambident phenolate anion can be useful in promoting palladium catalyzed couplings of phenols with aryl halides. A new procedure is described for the intramolecular coupling of phenols with aryl halides. This protocol represents a mild and selective method for forming carbon-carbon bonds to form hydroxylated biaryl products. The coupling is promoted by a novel palladacyclic catalyst, formed from Pd(OAc){dollar}sb2{dollar} and P(o-tolyl){dollar}sb3,{dollar} and is significantly accelerated using bases. There are a large number of natural products, such as vancomycin and the aporphine alkaloids, as well as interesting biaryls such as BINOL, which contain a highly oxygenated biaryl segment. Approaches towards actinoidic acid, a degradation product of vancomycin, and the pyrrolophenanthridine alkaloids are discussed.; Extension of this coupling procedure led to the development of a general route to hydroxylated indoles and benzofurans. Various substituted heterocycles were obtained using an intramolecular cross-coupling of vinyl halides with phenols. Although more delicate conditions were required for the coupling reaction to occur, the desired heterocycles were obtained in reasonable yields under mild, anionic conditions.; Attempts to utilize the anion-accelerated coupling with intermolecular reactions failed. In these attempts it was discovered, serendipitously that reductive homocoupling of aryl halides could be achieved using palladium catalysis in the presence of hydroquinone. This reaction was developed into a general method for the formation of symmetrical biaryls using both inter- and intramolecular coupling reactions.; The use of palladium catalysis in this novel anion-accelerated coupling reaction of phenols has led to methodology for the synthesis of hydroxylated cyclic biaryls, hydroxylated heteroaromatics, and symmetricalbiaryls. The reactions are general, occur under relatively mild conditions, and give good to high yields of the desired products. |
