Palladium 1,2-Migration

In the reaction of aryl and alkenyl halides with 1,3-pentadiene (248), amine and alcohol capture the 7r-allylpalladium intermediate to form 249. In the reactions of o-iodoaniline (250) and o-iodobenzyl alcohol (253) with 1,3-dienes, the amine and benzyl alcohol capture the Tr-allylpalladium intermediates 251 and 254 to give 252 and 255[173-175]. The reaction of o-iodoaniline (250) with 1,4-pen tadiene (256) affords the cyclized product 260 via arylpalladiuni formation, addition to the diene 256 to form 257. palladium migration (elimination of Pd—H and readdition to give 258) to form the Tr-allylpalladium 259, and intramolecular displacement of Tr-allylpalladium with the amine to form 260[176], o-Iodophenol reacts similarly. 

The palladium-catalyzed annulation of alkynes by functionally-substituted aryl and vinylic halides or triflates provides a veiy convenient and efficient approach to a wide variety of heterocycles and carbocycles. This chemistry has lead to the discovery of a number of novel palladium-catalyzed processes in which the palladium migrates from one carbon to another within the molecule providing a unique way to form carbon-carbon bonds in remote locations within the same molecule. 

About the same time that we discovered this aryl to aryl palladium migration chemistry, we observed a similar vinylic to aryl palladium migration process, which readily affords alkylidene fluorenes (Scheme 25).22 In this case,... 

Several different alkyl to aryl palladium migration processes have been also recently discovered using our standard palladium migration conditions (Scheme 28).24 Thus, both intramolecular Heck and intramolecular arylation... 

We believe that this novel new palladium migration chemistry provides a unique new way to generate a wide variety of organopalladium intermediates that will find considerable synthetic utility in the future. 

Zhao and Larock have described the synthesis of carbazoles, indoles, and dibenzofurans 118 via a Ic type cyclization that follows a sequence of Pd-catalyzed cross-coupling of alkynes and aryl iodides 116, then nitrogen-directed palladium migration to an arylpalladium intermediate 117 that undergoes an intramolecular Mizoroki-Heck ring closure <06JOC5340>. 

Many reactions have been recently reported, which involve palladium migration along an aromatic skeleton. For example, a Heck-type process led to the anticipated 3-substituted pyridyl, Heck product as well as a crossover product (Equation (157)). 

The proposed mechanism involves the initial oxidative addition of Pd(0) followed by a series of palladium migrations (Scheme 30). 

In spite of its formal similarity to the above mentioned annulation processes, the reaction shown in 4.37. includes a unique migration step. Oxidative insertion of the palladium into the phenyl-iodine bond is followed by the migration of the palladium onto the more electron rich indole ring. The 2-indolylpalladium complex than carbopalladates the pendant alkync moiety and the process ends by the formal activation of a C-H bond of the phenyl substituent and subsequent reductive elimination, furnishing the pentacyclic product.48 The same strategy has been utilised in the preparation of the indoloindolone framework from /V-bcnzoyl-3-(o-iodophcnyl)-indolc in an oxidative addition - palladium migration - C-H activation sequence.49... 

Table 2. Synthesis of fluorenones via 1,4-palladium migration and subsequent arylation of imines.

The final paragraph in this section details carbazole syntheses that involve the formation of C-C bonds. Intramolecular Diels-Alder cycloaddition of ynamides provided a new route to [b -fused carbazoles <05OL2213>. An electrocyclization of 2,3-divinylindole intermediates produced functionalized carbazoles <05TL4045>. A domino alkynylation/palladium migration/C-H activation approach to 4-vinylcarbazoles was reported <050L701>. For example, treatment of A-arylaniline 134 with diphenylacetylene in the presence of palladium acetate, cesium pivalate (CsPv), and bis(diphenylphosphino)methane (dppm) gave carbazole 136 via post-palladium migration intermediate 135. 

Using this concept the Sanford group found that direct C2-arylation of indoles and pyrroles could be effected under remarkably mild conditions with aryl iodo-nium salts and palladium(II) catalysts (Scheme 19) [42], The high C2 selectivity of the functionalization is attributed to a mechanism involving initial palladation at C3 followed by fast palladium migration to C2 under acidic conditions as initially proposed by Gaunt [43] and Sames [29], The reaction also works well for simple pyrroles, again with C2 selectivity. 

Palladium migration is a mechanistically interesting and synthetically useful process, because it provides an indirect approach to introduce palladium to a specific location in an organic molecule. It also allows C-H activation to occur on a remote site whose direct functionalization may not be easily achieved. Through the years, palladium migration processes have been applied to the construction of a variety of important heterocycles, such as carbazoles [25, 26], indoles [26], xanthones [27], and fluoren-9-ones [27, 28], They have also received special attention from computational chemists, who have conducted theoretical studies on the mechanism and transition state [29-31],... 

Other than palladium, rhodium is also known to perform similar migrations. Representative examples will also be briefly discussed. The palladium migration along alkyl chains via reversible P-hydride elimination/reinsertion processes will not be covered [32-36],... 

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