Heck reaction formate anions

A palladium-cataly/ed C-C coupling reaction—the Heck reaction — is used in the construction of bicyclic system 13. Cyclization leads to a q3-alIyl-Pd complex, which undergoes nucleophilic attack by malonic ester anion 12. This in turn leads to formation of the C4 side chain The mechanism of this reaction therefore differs from that of a normal Heck reaction. 

The quinoline 125 and the pyridone 126 are coupled by a base-catalysed SN2 reaction. Formation of the anion of the pyridone ensures attack at nitrogen (chapter 35). It only remains to close the ring by a Heck reaction.16... 

In a given reacting system, usually not all palladium is engaged in the catalytic process. The amount engaged depends on kinetics and the concentrations of reactants. The excess of palladium exists either in palladium(II) (102) or as palladium(O) (36) both are unstable under the conditions of Mizoroki-Heck reactions and should be protected (Scheme 2.23) palladium(II) (102) is unstable towards reduction if not protected in the form of an SRPC (102 103), palladium(0) (36) is unstable towards clusterization and growth of metal particles (36 —101 —70) and is protected by additives or components of reaction media in the form of anionic complexes 100 [36,84]. If we consider the reversibihty of formation... 

For previous reports of tandem Heck reaction-anionic capture sequences, see (a) Grigg, R., Sridharan, V. and Xu, L.-H. (1995) Palladium-catalyzed cyclization-amination of allenes - effect of base on regioselectivity of formation of allylic amines. J. Chem. Soc., Chem. Commun., 1903 and references cited therein (b) Ma, S. and Negishi, E. (1995) Palladium-catalyzed cyclization of general route to common, medium, and large ring compounds via cyclic carbopaUadation. J. Am. Chem. Soc., 117, 6345-7 and references cited therein. 

In further experiments, preformed TBAX-stabilized Pd-colloids were shown to interact with iodobenzene in a stoichiometric reaction with formation of Ph-PdX species, possibly in an ionic form as indicated by UVA is and NMR analysis. De Vries made the claim, (based on TEM, MS, EXAFS, filtration studies and Finke inhibition tests) that in standard Mizoroki-Heck reactions at high temperatures (>120 °C), the palladium catalyst is rapidly reduced to Pd(0) which tends to form soluble colloids. The atylating agent continuously attacks the palladium atoms at the rim of the nanoparticles leading to the formation of soluble anionic complexes, completion of a Mizoroki-Heck cycle in solution. 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

Another sequence involving an anionic and a Pd-catalyzed step was described by the groups of Rossi and Arcadi [477]. These authors prepared substituted tetrahy-dro-2H-pyrrolo[3,2-c]pyrazolones 2-934 starting from hydrazones 2-932 and aryl-halides or alkenyl triflates 2-933 (Scheme 2.208). The first step is the formation of a pyrazolone. There follows cleavage of the urea moiety with piperidine and an inter-as well as an intramolecular Heck-type reaction with 2-933. 

The formation of compound 175 could be rationalized in terms of an unprecedented domino allene amidation/intramolecular Heck-type reaction. Compound 176 must be the nonisolable intermediate. A likely mechanism for 176 should involve a (ji-allyl)palladium intermediate. The allene-palladium complex 177 is formed initially and suffers a nucleophilic attack by the bromide to produce a cr-allylpalladium intermediate, which rapidly equilibrates to the corresponding (ji-allyl)palladium intermediate 178. Then, an intramolecular amidation reaction on the (ji-allyl)palladium complex must account for intermediate 176 formation. Compound 176 evolves to tricycle 175 via a Heck-type-coupling reaction. The alkenylpalladium intermediate 179, generated in the 7-exo-dig cyclization of bro-moenyne 176, was trapped by the bromide anion to yield the fused tricycle 175 (Scheme 62). Thus, the same catalytic system is able to promote two different, but sequential catalytic cycles. 

---