Heck-Coupling Route

1 Preparation of Poly[2,5,2,5 -tetraoctyl-p-terphenyl-4,4-ylenevinylene-p-phenylene vinylene] (91) (Chart 2.149) 

From Hilberer, A., Brouwer, H.-J., van der Scheer, B.-J., Wildeman, J., and Hadziioannou, G., Macromolecules, 28 4525-4529, 1995. Copyright 1995, American Chemical Society, Washington, D.C. With permission. 

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Brown Ripin, D.H., Bourassa, D.E., Brandt, T. et al. (2005) Evaluation of kilogram-scale Sonagashira, Suzuki, and Heck coupling routes to oncology candidate CP-724,714. Org. Process Res. Dev., 9, 440-50. 

The first reaction pathway for the in situ formation of a metal-carbene complex in an imidazolium ionic liquid is based on the well loiown, relatively high acidity of the H atom in the 2-position of the imidazolium ion [29]. This can be removed (by basic ligands of the metal complex, for example) to form a metal-carbene complex (see Scheme 5.2-2, route a)). Xiao and co-workers demonstrated that a Pd imida-zolylidene complex was formed when Pd(OAc)2 was heated in the presence of [BMIMjBr [30]. The isolated Pd carbene complex was found to be active and stable in Heck coupling reactions (for more details see Section 5.2.4.4). Welton et al. were later able to characterize an isolated Pd-carbene complex obtained in this way by X-ray spectroscopy [31]. The reaction pathway to the complex is displayed in Scheme 5.2-3. 

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... 

Transition metal catalyzed insertion reactions offer a convenient route for the preparation of five membered heterocyclic rings. Besides intramolecular Heck-couplings and CO insertion, examples of the intramolecular insertion of an acetylene derivative constitute the majority of this chapter. Although some of these processes involve the formation of a carbon-heteroatom bond, they are discussed here. 

The stilbazoles have been synthesized using three different routes, and these are now described briefly (Figs. 2 and 3). The first attempts involved reacting 4-alkoxybenzaldehyde with 4-picoline in acetic anhydride, which led to extremely poor yields of the stilbazoles after a week s work (2). This route was subsequently superseded by a Heck coupling method in which 4-vinylpyridine was reacted with 4-alkoxyiodobenzene in the presence of a palladium catalyst (2). The reaction worked very... 

Emmons reaction (Scheme 26). ° Horner-Wadsworth-Emmons reactions also feature in new routes to (diphenylphosphono)acetic acid esters and alkenes. The latter involve combining the Homer-Wadsworth-Emmons procedure with a Heck coupling reaction for the synthesis of tri-substituted alkenes. 

A second approach to the indolo[3,2-c /]benzazepinone system was also reported in 2005 by Joseph and coworkers. This involved a neat route based on 3-substituted indole derivatives and an intramolecular Heck coupling to form the 12a-12b bond in the fused ring system <05TL8177>. 

An efficient route to the synthesis of the cytotoxic pyrrolo[2,l-c][l,4]benzodiazepines 97-99 with conjugated C2-acrylyl substituents based on a Heck coupling of 96 to introduce this C2 side-chain. The route started from the nitro benzoic acid 93, and proceeded via standard transformations to 94, which was then cyclised to the 7-membered ring derivative 95 on oxidation of the primary alcohol to the aldehyde <04BMCL1547>. 

Scheme 4.5 shows the most important direct routes for preparing soluble PAVs Heck coupling, and Wittig and Horner polycondensations. The two biggest advantages of these routes are that they avoid the formation of tolane and other defects seen in the precursor routes, and also that they allow the synthesis... 

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