The Heck Coupling

In aqueous DMF, the reaction can be applied to the formation of C-C bonds in a solid-phase synthesis with resin-bound iodobenzoates (Eq. 6.33). ° The reaction proceeds smoothly and leads to moderate to high yield of product under mild conditions. The optimal conditions involve the use of 9 1 mixture of DMF-water. Parsons investigated the viability of the aqueous Heck reactions under superheated conditions. A series of aromatic halides were coupled with styrenes under these conditions. The reaction proceeded to approximately the same degree at 400°C as at 260°C. Some 1,2-substituted alkanes can be used as alkene equivalents for the high-temperature Heck-type reaction 

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The coupling reaction of aryl-alkenyl halides with alkenes in the presence of a palladium catalyst and a base is known as the Heck coupling (Scheme 9.4).6 Since the early 1980s, this type of coupling reaction has been used for die syndiesis of poly(arylenevinylene) and related polymers by polymerization of AB- or AA/BB-type of monomers (Scheme 9.5).7... 

OUTLINE OF THE CATALYTIC CYCLE FOR THE HECK COUPLING REACTION... 

Another methodology that is widely used for C-C bond formation is the Heck coupling (Heck, 1985 T.suji, 1995). The Heck reaction involves the palladium-catalysed arylation of olefinic double bonds (Eqn. (12)) and provides an alternative to Friedel-Crafts reactions for attaching carbon fragments to aromatic rings. 

The Heck coupling reaction appeared to be a route of choice to achieve the synthesis of the modified-DIOP ligands. We previously studied the palladium-catalyzed coupling of acrolein and acrolein acetals with several polyaromatic and heteroaromatic bromides either in the presence of homogeneous or heterogeneous catalytic systems (6, 7). After optimization of the reaction conditions, high conversions and selectivities were achieved except with anthracenyl derivatives (8). Based on these results, we developed the synthesis of the desired ligands. The... 

To overcome this drawback, we studied the arylation of diethyl 2-vinyl-[l,3]-dioxolane-4,5-diacetate 2 with several bromo polyaromatic and heteroaromatic substrates (Table 21.1 and Scheme 21.4). In parallel, the Heck coupling of several vinyl dioxolane derivatives with aryl bromides was studied in the presence of homogeneous catalysts (Table 21.1). 

Similarly, the Tietze group has described an intramolecular microwave-promoted Heck reaction for the construction of the B ring in the synthesis of enantiopure B-nor-estradiol analogues (Scheme 6.10 a) [29]. The Heck coupling took place from below, anti to the angular methyl group, to form a single diastereoisomer. The best... 

Somei and co-workers made extensive use of the Heck reaction with haloindoles in their synthetic approaches to ergot and other alkaloids [26, 40, 41, 240-249]. Thus, 4-bromo-l-carbomethoxyindole (69%) [26], 7-iodoindole (91%) (but not 7-iodoindoline or l-acetyl-7-iodoindoline) [40, 41], and l-acetyl-5-iodoindoline (96%) [41] underwent coupling with methyl acrylate under standard conditions (PdlOAc /PhsP/EtjN/DMF/100 °C) to give the corresponding (E)-indolylacrylates in the yields indicated. The Heck coupling of methyl acrylate with thallated indoles and indolines is productive in some cases [41, 241, 246]. For example, reaction of (3-formylindol-4-yl)thallium bis-trifluoroacetate (186) affords acrylate 219 in excellent yield [241], Similarly, this one-pot thallation-palladation operation from 3-formylindole and methyl vinyl ketone was used to synthesize 4-(3-formylindol-4-yl)-3-buten-2-one (86% yield). 

Other Pd(II) complexes with imidazole-like ligands were also specifically synthesized for improved solubility in ionic liquids (258). The catalysts were applied for the Heck Coupling of iodobenzene with -butyl acrylate in [BMIM]PF6 in the presence of Et N at 120°C. One catalyst (Scheme 27) was especially well retained without any loss of activity even at fairly low catalyst loading (0.2mol%) for more than five repeated uses. In all cases, > 99% yield was achieved within 1 h. 

The Heck coupling is also efficient in the formation of pyrane derivatives. By starting from the appropriately substituted 1,3,5-tribromobenzene derivative, three fused pyrane rings were constructed in the same reaction. The triple Heck reaction in the presence of palladium acetate and triphenylphosphine led to the formation of the tetracyclic product in good yield accompanied by a minor amount of the tricyclic intermediate(4.12.).13... 

An example of the Heck coupling of oxazols is presented in 6.60. The 5-bromooxazole derivative reacted with styrene under standard conditions to give the expected styryloxazole in 87% yield. Coupling of the regioisomeric... 

The ready insertion of carbon monoxide into furanylpalladium complexes is impressively demonstrated by the reaction depicted in 6.63. The iodofiirane derivative was reacted with carbon monoxide in the presence of tetrabutylammonium chloride. Following an aqueous workup the appropriate carboxylic acid was isolated in good yield (6.63.).94 It is worth pointing out, that due to the mildness of the reaction conditions the Heck coupling of the olefin moiety could be excluded. 

Initial studies showed that the encapsulated palladium catalyst based on the assembly outperformed its non-encapsulated analogue by far in the Heck coupling of iodobenzene with styrene [7]. This was attributed to the fact that the active species consist of a monophosphine-palladium complex. The product distribution was not changed by encapsulation of the catalyst. A similar rate enhancement was observed in the rhodium-catalyzed hydroformylation of 1-octene (Scheme 8.1). At room temperature, the catalyst was 10 times more active. For this reaction a completely different product distribution was observed. The encapsulated rhodium catalyst formed preferentially the branched aldehyde (L/B ratio 0.6), whereas usually the linear aldehyde is formed as the main product (L/B > 2 in control experiments). These effects are partly attributed to geometry around the metal complex monophosphine coordinated rhodium complexes are the active species, which was also confirmed by high-pressure IR and NMR techniques. 

In addition to being a synthetically useful by-product, the isolation of 44 suggested that the moderate yields of the Heck coupling were due to fi-elimination of the butenyl side chain, perhaps via an intermediate palladium amide complex. While the reason for the readiness of this E-butenyl geometry to undergo elimination is unclear, it is clearly a facile process, having been observed several times previously (as noted). 

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