Intermolecular reactions cascade carbopalladation

In their pioneering work on the catalytic carbopalladation reaction of 1,2-heptadiene with phenyl iodide in the presence of a suitable base, Shimizu and Tsuji observed the formation of the corresponding substituted 1,3-dienes 62 via a / -hydride elimination from the 7z>allyl intermediate 61 [61]. Based on these observations, a three-component Heck-Diels-Alder cascade process has been developed by Grigg and co-workers [73]. A wide variety of aryl and heteroaryl iodides were used for the intermolecular reaction with dimethylallene to afford the corresponding 1,3-dienes. These subsequently react in situ with N-methylmaleimide to give the bicyclic adducts 63 (Scheme 8.30). 

As discussed in conjunction with the intermolecular cascade carbopalladation reaction shown in Scheme 4, it has been very difficult to satisfactorily control both queuing or pair -selectivity and regioselectivity of intermolecular cascade carbopalladation processes. Consequently, essentially all of the cascade carbopalladation reactions discussed here are at least partially intramolecular. The currently known cyclic cascade carbopalladation processes can be classified into a few to several types shown in Scheme 6. 

Grigg and Xu have developed a variety of so-called queuing cascades involving allenes. The intra-intermolecular carbopalladation sequence of the <9-iodo-A-methyl-A -(methylallyl)aniline 142 and 1,1-dimethylallene 143 with subsequent / -dehydropalladation leads to the 1,3-dienyl-substituted indole derivative 144, which is immediately trapped by an added dienophile (e.g., A-methylmaleimide) in a Diels-Alder reaction to yield 145 (Scheme 37)7 ... 

There are at least two issues to be addressed regarding the Type lie circular cascade process shown in Scheme 42. One is the regioselectivity in the initial intermolecular carbopalladation. Since it is not very difficult to differentiate the two terminal positions of a. j-diyncs, this is not a serious problem in most cases. A more serious problem is the exclusive formation of fulvene derivatives observed in a couple of cases [124] (Scheme 45). It is not very clear what the scope of the fulvene formation is and whether the course of the reaction could be altered to give benzene derivatives. 

In 2009, Kemmerer et al. uncovered a phosphine-free carbopalladation/allylic alkylation cascade sequence for the synthesis of 4-(a-styryl) y-lactams 308 [106] (Scheme 6.79). The reaction pathway of this transformation involves the formation of Jt-allylpalladium(n) species 307, which was trapped by the intermolecular active methylene. Both electron-rich and electron-deficient aryl iodides could be introduced efficiently to this cascade process. Li and Dixon developed a stereoselective and efficient protocol for the synthesis of spirolactam 310 employing a similar carbopalladation/jt-allylpalladium trapping strategy [107] (Scheme 6.80). 

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