Heck oxime-derived palladacycle

In a recent article by Botella and Najera, controlled mono- and double-Heck arylations in water catalyzed by an oxime-derived palladacycle were described [22], When the reaction was carried out under microwave irradiation at 120 °C in the presence of dicyclohexylmethylamine with only 0.01 mol% of palladium catalyst (palladium acetate or palladacycle), monoarylation took place in only 10 min with a very high turnover frequency (TOF) of > 40000 (Scheme 6.3). As regards diarylation, 1 mol% of the palladacycle catalyst and 2 equivalents of iodobenzene had to be utilized to obtain moderate to good yields of diarylated product. Whereas microwave heating at 120 °C provided a 31% yield after 10 min, a 66% isolated yield of product was obtained by heating the reaction mixture under reflux for 13 h at 100 °C. Here, the... 

Scheme 6.3 Mono- and double-Heck arylations in water using oxime-derived palladacycles.

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

More recently, Najera et al. performed a number of Heck reactions of deactivated aryl halides and styrenes under phosphane-free conditions using oxime-derived palladacycles or palladium acetate as catalyst [113], Coupling can be performed either vith chcyclohexylmethylamine as base and TBAB as PTC catalyst or in neat vater vith triethylamine in N,N-dimethylacetamide (DMA) solutions under the action of MW irradiation. 

Coelho et al. have developed an improved and highly efficient synthesis of several a-benzyl-p-ketoesters 128 by using MBH adducts as substrates for an intermolecular Heck reaction catalyzed by a Najera oxime-derived palladacycle (129). These efficient catalytic conditions proved to be high selectivity and only provided the corresponding functionalized p-ketoesters 128 in high yields with no decarboxylation products (Scheme 3.50). ... 

Figure 15.4 Kaiser oxime-derived palladacycle 54 applied in Mizoroki-Heck catalysis in neat water.

Botella, L. and Najera, C. (2004) Controlled mono and double Heck reactions in water catalyzed by an oxime-derived palladacycle. Tetrahedron Lett., 45, 1833-6. 

Alacid E, Najera C (2008) The Mizoroki-Heck reaction in organic and aqueous solvents promoted by a polymer-supported Kaiser oxime-derived palladacycle. ARKIVOC viii... 

Alternative solvents have been developed for the Heck-Matsuda reaction. This reaction has recently been performed in neat water by Najera s group [95]. The reaction was carried out using an oxime-derived palladacycle catalyst and palladium acetate using a variety of different diazonium tetrafluoroborates giving styrenes, stllbenes, arylideneketones, and cinnamate esters (Figure 1.26). 

As conclusion, the high catalytic efficiency of the polymeric palladacycle derived from Kaiser oxime resin similar to that of related unsupported dimeric pal-ladacycles was observed in the Mizoroki-Heck reaction. This polymer showed a good catalytic activity, not only in organic but also in aqueous media, for aryl iodides, bromides, and activated chlorides with high turnover numbers (TONs), rmder aerobic conditions at relatively lower temperature. 

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