Carbomethoxy cycle

Fig. 6 The carbomethoxy cycle (a), the hydride cycle (b) and the shift of the hydride mechanism to the other (c) (S = CH3CN). Adapted from [58]...

It is interesting to point out that with this catalyst formation of MP occurs also through the carbomethoxy cycle, whereas it will be shown that most catalysts that are highly selective to MP operate through the hydride mechanism (see Fig. 6). 

The carbomethoxy cycle starts with the attack of a methoxy group at a coordinated carbonyl group or a migratory insertion of CO in a palladium methoxy bond. Any type of methoxy species will have a low concentration in the acidic medium of the reaction. In Figure 12.20 many details of these reactions, discussed above in section 12.2, have been omitted and only a shorthand notation is presented. Subsequently insertion of ethene takes place. It is known from stoichiometric experiments that both reactions are relatively slow. In the final step a formal protonation takes place, which as we saw before, may actually involve enolate species. 

Palladium(O) forms a complex with quinone that is now electron rich and can be protonated to give hydroquinone and palladium(II). The latter can start a new cycle via a carbomethoxy species after reaction with methanol and CO (c.f. reaction (6), Figure 12.4). Thus we have formally switched from a hydride initiator to a carbomethoxy initiator species. Addition of quinone to a nonactive or moderately active palladium system is a diagnostic tool that tells us whether zerovalent palladium is involved as an inactive state. Likewise, one might add dihydrogen to a system to see whether palladium(II) salts need to be converted to a hydride to reactivate our dormant catalyst. 

Fig. 7 The hydride (A) and the carbomethoxy (B) cycles, with shift from the latter to the first through the action of H2O...

The other cycle starts from the other end of the MMA molecule by carbon monoxide insertion in a Pd-methoxy species, followed by propyne insertion in the 7,2 regio-mode in a Pd-carbomethoxy bond and subsequent termination by protonolysis of the Pd-alkenyl bond to give MMA and a regenerated Pd-methoxy species (Scheme IB). In this cycle, methyl crotonate is formed by insertion in the 2,1 regio-mode. 

This implies that the other elementary steps in cycle B (Scheme 1), i.e., Pd-carbomethoxy formation and protonolysis of the palladium-alkenyl species, must even be considerably faster than the observed overall high reaction rate. A high rate of Pd-carbomethoxy formation (at equilibrium) could be expected for the strongly electrophilic metal center. However, the latter step, protonolysis of the Pd-alkenyl bond in l-palladium-2-carbomethoxypropene and 2-palladium-1-car-bomethoxypropene, respectively, is expected to be a slow reaction, because the proton has to overcome a relatively high barrier of (electrostatic) repulsion by the cationic palladium center on its way to the palladium-carbon bond. 

Figure S Redrawn and modified model of topoisomerase 11 catalysis as proposed by Roca and Wang (159). Doxorubicin, daunorubicin, other 10-descarbomethoxy anthracyclines, and other topoisomerase 11 poisons" inhibit topoisomerase II activity by stabilization of the "cleavable com-ptex" (i.e., freezing the catalytic cycle between steps 3 and 4), which results in an accumulation of DNA strand breaks, and ultimately, DNA degradation. Aclarubicin and possibly other anchracy-dines possessing the 10-carbomethoxy moiety inhibit topoisomerase II by inhibiting reaction 1, namely, the complexaiion of DNA and the enzyme.

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