Heck reaction on solid support

In the final example of the Heck reaction on solid support, a Chiron group54 55 used a palladium-catalyzed cyclization step to prepare heterocycles. An example of their work, the production of l-(2H)-isoquinolinones, is shown in Scheme 22. 

Arumugam, V. Routledge, A. Abell, C. Balasubramanian, S. Synthesis of 2-Oxindole Derivatives via the Intramolecular Heck Reaction on Solid Support, Tetrahedron Lett. 1997, 38, 6473-6476. 

Yun, W. Mohan, R. Heck Reaction on Solid Support Synthesis of Indole Analogs, Tetrahedron Lett. 1996, 37, 7189-7192. 

Intramolecular formation of large rings can be carried out efficiently on solid support, which may help to suppress competitive intermolecular reactions, as illustrated by some recent examples Macrocyclisation of the acrylamido peptide-3-iodobenzylamide 13 via Heck reaction on solid support proceeds more rapidly than the corresponding solution phase reaction22 (Scheme 1.6.5). 

Even selective 7-exo-cylizations [25] have been reported via intramolecular Mizoroki-Heck reactions on solid supports. One synthesis deUvers bicyle 25 in 60% overall yield (Scheme 14.7) [25]. 

Other major issues are the aspects of stereo- and regio-chemistry. Compared with its liquid-phase variant, where tremendous efforts have been made over recent years to develop chiral ligands and optimize procedures of enantio- and diastereo-selective syntheses of complex molecules, the Mizoroki-Heck reaction on solid supports is still in its infancy. Most libraries, indeed, contain racemates and mixtnres of diastereomers [11],... 

Heck reactions on solid supports have been extensively applied because of the easy accessibibty of starting materials such as polymer-bound haloalkenes or haloarenes and alkenes. The most frequently used reaction conditions are either the standard Heck conditions (Pd(OAc)2, PPhj, or P(o-Tol)3, DMF, 80-100°C,... 

B.ii.c. Intramolecular Heck Reactions. The main advantage of intramolecular Heck reactions on solid support is the pseudodilution of the starting material leading to an increase of the yield. The first use of this was reported in 1995 for the synthesis of 20- to 24-membered macrocyclic ring systems (Scheme 3). ... 

Ruhland et al. used both the Suzuki and Heck (see above) reactions on solid support in their generation of libraries of biaryl- and styryl-substituted [3-lactams.45 A preliminary investigation was performed into the most generally suitable catalytic system for preparation of their libraries. This featured coupling of phenylboronic acid with a resin-bound iodophenyl [3-lactam 32 (Scheme 36) the latter compound had been formed from a... 

Over the past 5 years the number of reports on the use of palladium-catalyzed reactions for solid-phase derivatizations has greatly increased. In this section (and throughout this chapter), we limit our scope to representative applications for the modification of solid-supported heterocyclic scaffolds. A more general overview of the versatility of Suzuki, Heck, and Stille reactions on solid supports was recently provided by Franzen.32... 

Franzen has recently presented a review on the Suzuki, Heck, and Stille reactions on solid supports [110]. 

Scheme 5 Sequential Heck-amination reaction on solid support [64]...

Since the renaissance of solid-phase organic chemistry in 1992, carbon-carbon bond formation reactions on solid support have probably been the best studied reactions. Many different facets of the Suzuki, Heck and Stille reactions have been evaluated. The influence of linkers, catalyst, solvents, microwave, polymer-bound aryl halides or polymer-bound arylboronic acids (or stannanes) have been studied in detail. 

B.xiv.c. Intermolecular Heck Reactions on Polymeric Support. Combinatorial chemistry has initiated a reappraisal and consequent renaissance in synthesis of compounds attached to polymeric supports. Therefore, it comes as no surprise that Pd-catalyzed reactions are among the most widely explored reactions for the generation of combinatorial libraries on solid phase. The first example of the intermolecular Heck reaction on solid phase was reported in 1994. In this article, 4-vinylbenzoic acid was attached to Wang resin and coupled with aryl halides/triflates under catalysis with Pd(OAc)2 (Scheme 45). Similar... 

There are, however, some problems that can be encountered using Mizoroki-Heck coupling reactions on solid supports. Sometimes, when soluble supports are used, the removal of the catalyst and of the excess of reagents may not be that trivial. In order to circumvent this problem, people are constantly looking for solntions. One may be the development of new solid snpports [29, 30] another even more promising approach is the... 

Heck, Sonogashira and Suzuki reactions on solid supports (a) Dohele,... 

An intramolecular Heck cyclization strategy was developed for the construction of indole and benzofuran rings on solid support [82], enabling rapid generation of small-molecular libraries by simultaneous parallel or combinatorial synthesis. Sn2 displacement of resin-bound y-bromocrotonyl amide 97 with o-iodophenol 96 afforded the cyclization precursor 98. A subsequent intramolecular Heck reaction using Jeffery s ligand-free conditions furnished, after double bond tautomerization, the resin-bound benzofurans, which were then cleaved with 30% TFA in CH2CI2 to deliver the desired benzofuran derivatives 99 in excellent yields and purity. 

C-C bond formation using the Heck reaction allows the introduction of functional groups to obtain new organic structures on solid supports. This reaction between an alkene with an alkenyl or an aryl halide has been widely employed in various in-tra- and inter-molecular versions on solid-phase because of the readily accessibility of starting materials. The Heck reaction was performed on immobilized aryl or alkenyl halides with soluble alkenes and vice versa (Scheme 3.11). 

Spear et al. chose the Heck reaction to elaborate 4-iodophenylsulfonyl chloride attached to Rink amide resin, that is, sulfonamide 18.43 The reaction (Scheme 16) was reported to be quantitative, as was a simple Stille coupling on the same molecule. Raju and Kogan used a Suzuki coupling on solid support (see below)44 to illustrate use of a new carbamate linker for the generation of more diverse sulfonamides than those above. 

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