Heck alkenylation

Heck reactions. Heck alkenylation of 2-, 3-, or 4-bromo- or -iodopyridines with monosubstituted alkenes is most commonly achieved by heating in the presence of catalytic quantities of palladium(II) acetate, triarylphosphines, and a base such as triethylamine <20050L363> or potassium carbonate <2005S2193>. 

Thus, a domino-Heck-Michael reaction has been reported by Yamada and co-workers [87]. This transformation allowed the formation of three contiguous cycles in one single operation. The mechanism involves first a Heck alkenylation of the iodide 95 which after a /1-hydride elimination step leads to intermediate 96 which undergoes attack of the a-nitro group carbanion to produce the tricyclic compound 97 (Scheme 37). 

In 1999, Ravina and co-workers described the first example of an intermolecular Heck reaction on a pyridazine derivative [73]. Heating 5-bromo-2-methoxymethyl-6-phenylpyridazin-3(2//)-one (172) with styrene at 120°C for two days in a pressure tube, using Pd(OAc)2/PPh3 as the precatalyst and triethylamine as the base in acetonitrile, yielded 2-methoxymethyl-6-phenyl-5-(2-phenylvinyl)pyridazin-3(2//)-one in moderate yield (40%). Later, the same research group published more examples of Heck alkenylations on the same substrate with alkyl acrylates and acrylonitrile [93]. The catalyst and base were the same, but acetonitrile was replaced by DMF as the solvent. N-l protection of the pyridazin-3(2//)-one was essential for the alkenylation to occur since no formation of the desired reaction product could be observed on 5-bromo-6-phenylpyridazin-3(2//)-one (6) itself. Instead, Michael addition of the N-2 nitrogen on the alkyl acrylates and acrylonitrile occurred. Besides this... 

The Pd-catalyzed coupling reaction of an aryl halide and olefin is a very efficient and practical method for making C—C bonds. The Heck alkenylation of aryl bromides with ethylene was used by Dow Chemical to make high-purity 2- and 4-vinyltoluenes, which are of interest as co-monomers in styrene polymers [159]. The monomer, o-vinyltoluene (99), has a low toxicity and an attractive co-monomer for styrene polymers. o-Vinyltoluene improved heat distortion properties of styrene and polymerization rate. It also minimized color formation or cross-linking and it was difficult to make by other routes [159]. Catalyst turnover, rate, and lifetime were significantly improved. 

The reactivity of pyridazines in Pd-catalyzed reactions was of interest. For example, the Heck alkenylation at C5 of 6-phenyl-3(2//)-pyridazinones was investigated, with the aim of suppressing production of 4-phenyl-6-substituted-2-phthalazinone byproducts <04TL3459>. In another study, the reactivity of 5-iodopyridazin-3(2f/)-ones in Pd-catalyzed reactions was investigated to develop an efficient route to 2,5-disubstituted pyridazin-3(2/f)-ones <04T12177>. Other pyridazine syntheses relied on condensation approaches. Benzo[g]pyridazino[l,2-i>]-phthalazine-6,13-diones 16 and 17 related to certain anthracyclinones were obtained by cycloaddition of 1,3-dienes to benzo[g]phthalazine-l,4-dione <04H(63)1299>, and pyridazine C-nucleosides synthesized by 14-i-2 cyclocondensation of alkynyl C-nucleosides with substituted tetrazines afforded, upon extrusion of a nitrogen atom, pyrrole C-nucleosides in good yields... 

In the case of intermolecular Heck alkenylation of vinyl triflate and 2,2-disubstituted-2,3-dihydrofiiran, Proton Sponge (1) gave higher chemical yield and enantioselectivity compared to the trialkylamines [35] (Table 8.10). 

Tin Reagents. In the -Tr-excessive systems alkenylation has often been carried out with the metallated heterocycle vide supra). Also widely used are Heck alkenylations vide infra). Coupling of vinylstannanes with 3-iodoindoles was used in the preparation of 3-alkenylindoles 51 (Scheme... 

The hydroarylation of aHc5mes, which has emerged as a powerful alternative to the oxidative arylation of alkene, is not discussed in this chapter as it is not a true Heck alkenylation. Jia, C., Piao, D., Oyamada, J. et al. (2(X)0) Efficient activation of aromatic C—H bonds for addition to C—C multiple bonds. Science, 287,1992-5. 

In a seminal communication, Chiusoh et al. reported an example of an intercepted Mizoroki-Heck reaction for the first time [86]. A palladiumreducing agent, ammonium formate, produced a mixture of 146 and 147 in a reaction temperature-dependent ratio (Scheme 7.34). The minor product 147 was formed by standard intermolecular Mizoroki-Heck alkenylation and subsequent reductive cleavage of the intermediate C(sp )—Pd" bond formation of the major product 146 involved an additional intramolecular alkene insertion prior to the reduction step. 

Scheme 3.19 Synthesis of ethyl undeca-2,4-dienoates by Heck alkenyl-alkenyl coupling and its scope and limitations [104, 109].

Table 3.8 Current scopes of the conjugated diene syntheses by Negishi and Heck alkenylations as well as by HWE and SG A olefinations... 

Tetrasubstituted furans were prepared by tandem furan formation/dehydro-genative Heck alkenylation under Cu/Pd relay catalysis (Scheme 2.90) [145]. 

Scheme 2.90 Tandem furan fbrmation/dehydrogenative Heck alkenylation of cyclopropene.

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