C-H Activation Reactions in Domino Processes

Domino Reactions Concepts for Efficient Organic Synthesis, First Edition. Edited by Lutz F. Tietze. 

While intramolecular C-H activations have been successfully incorporated in the domino Heck reactions, the intermolecular C-H activations with external 

The activation of the C-H of ring B (Path b) to five-membered palladacyde 36 was not observed, which would lead to the fluorene derivative 37 via a vinyl to aryl Pd migration and cyclization [13]. 

By employing a benzyne precursor 61, isochromenone 62 and oxepine 63 were synthesized in good yields from alkynes 59 and 60, respectively. The proposed 

Subsequent C-H activation generates the five-membered paUadacycle 65, which undergoes intermolecular carbopalladation with aryne 66 to give seven-membered paUadacycle 67. FinaUy, reductive ehmination furnishes the product 62 and regenerates the palladium catalyst. Overall, three C-C bonds are constructed in this reaction sequence. In an earher report, Tanaka and coworkers [23] had observed similar domino reactions with bromoenynes to synthesize benzoisoindoles in the absence of external benzyne acceptors. 

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The combination of a Mizoroki-Heck reaction with a C—H activation is a domino process that has been encountered with increasing frequency in the past few years. This type of transformation takes place if the organo-palladium intermediate does not react in the usual way but activates an aryl- or vinyl-H bond in close vicinity, forming a new palladium(II) species that can react further with electrophiles or nucleophiles and giving rise to the formation of another C—C or C-Tieteroatom bond. 

Jia and coworkers [71] reported a very nice palladium-catalyzed domino reaction involving a C-H activation process (Scheme 12.47). The regioselectivity of the attack of the nucleophile at the intermediately formed palladacyle 121 is solely controlled by the reaction conditions using the same substrate. In the Pd-catalyzed transformation of 120 in DMF in the absence of water, the aryl-substituted product 122 was obtained in 47-95% yield, and, in the presence of water, the alkyl-substituted product 123 in 60-95% yield. However, it should be noted that the reaction temperature has also some influence. The paUadacycle intermediate 121 was successfully trapped by cyanation, Heck reaction, secondary C-H activation, and Suzuki coupling. 

Under ruthenium-catalyzed ortho-C-H activation and intramolecular C-N bond formation, the condensation of iminophosphoranes (in situ generated from acyl azides and triphenylphosphine) with internal alkynes afforded a variety of isoquinolinone derivatives (Eq. (7.43)) [53]. The regioselective insertion of unsymmetrical alkynes led to an (aryl)C-N bond formation. Thiophene and indole-based acyl azides were also compatible for this transformation. A domino reaction sequence via coordination of ruthenium with Af-atom of iminophosphoranes, ort/zo-cyclometalation, alkyne insertion, protonation, and reductive elimination was proposed for the catalytic cycle. Based on and NMR experiments, the involvement of benzamide during the reaction process was ruled out. 

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