Palladium-Mediated Ring Closure

The synthesis of kinafluorenones, which are of interest for the synthesis of Strepto-myces-related antibiotics, has been investigated by Jones [52]. The palladium-mediated ring closure depicted in Eq. (11.36) resulted in poor yields under conventional heating but irradiation with a domestic microwave oven for 60 s improved the yield substantially. 

Palladium-Mediated Ring Closure A Well-Trodden Path With a New Destination... 

An nice example of the formation of a five membered ring in crosscoupling reaction is the hexamethyldistannane mediated ring closure of the dihalogenated diaryl ether shown in 3.1. The first step of the process is the palladium catalyzed exchange of one of the iodides to a trimethylstannyl moiety, followed by the closure of the five membered ring in Stille coupling. 

The combination of the formation of palladium(II) complexes in the oxidative addition of unsaturated halides onto palladium(O), and the palladium(II) mediated ring closure of olefins allows for the elimination of the oxidant. The ring closure of the methallyl-aniline derivative shown in 3.67. in the presence of /J-bromostyrcnc and a catalytic amount of palladium led to the ring closed - coupled product.84 The ring closure might also be accompanied by other follow-up reactions. 2-Methallyl-anilines were converted for example to indolylacetic acid derivatives in the presence of carbon monoxide.85... 

Iodo-l-(3-methylbut-3-enyloxy)-4-phenoxybenzene 461 undergoes palladium(n)-mediated ring closure via a 1,4-shift of palladium from alkyl to aryl followed by intramolecular arylation to afford the fused chroman 462 (Equation 190) <2004JA7460>. Similarly, l-iodo-2-(3-methylbut-3-enyloxy)benzene can undergo a palladium(n)-mediated cyclocarboformylation to afford the chroman 463 (Equation 191) <2001T1347>. 

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

The ability of palladium(II) acetate to mediate the oxidative ring closure of indole derivatives containing a pendant aromatic ring has been exploited... 

Besides the synthetic route depicted in 5.5. the seven membered central heterocyclic ring of iboga alkaloids was also accessed by the palladium mediated closure of the indole derivative bearing a pendant double bond shown in 5.21. The reaction is believed to be initiated by the palladation of indole in the 2-position followed by insertion of the double bond. Since fi-hydride elimination from the formed intermediate is blocked by the conformational rigidity of the system, the reaction stops at this stage and the addition of a reducing agent is required to remove the palladium and obtain the product.21... 

Carbon-carbon bond formation resulting in ring closure is important in synthesis, especially so if the process is general. A potentially very useful method whereby silyl enol ethers undergo palladium(n)-mediated intramolecular cycliz-ation with alkenes is therefore noteworthy (Scheme 26). Although we illustrate just one example in the Scheme, many others were investigated, including an application for the formal total synthesis of ( )-quadrone. ... 

In a concise synthesis of 15,16,17,18,19,20-hexahydroyohimbane (461), Pandey and Tiwari also utilized D-ring closure as the final step in a sequence for generation of the yohimbane skeleton (Scheme 3.80). Cyclization of the amino-aryl bromide 459 was achieved by a palladium-mediated carbon monoxide insertion reaction. The resulting amide 460 was reduced to provide the desired target 461. 

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