Cyclizative Heck coupling

Cyclizative Heck coupling. This reaction is highly regioselective in the case of a,p-unsaturated carbonyl compounds such as 1 and 3.2... 

A sequence of an inter- and an intramolecular Heck coupling has been used to construct the 26-membered carbocyclic compound 60 from an acyclic precursor 59, which presents half of the target molecule (Scheme 20). The first step of this twofold coupling is favored to occur inter- rather than intramolecularly, because the latter would lead to a highly strained 13-membered ring system with a biaryl unit and a frans-configmed double bond. In the cyclizing second step, polymerization is disfavored by the orientation of the two side arms in the 3- and 3 -positions of the initially formed 1,1 -biaryl derivative. 

Scheme 20 Inter-intramolecular Heck coupling sequences with cyclizations leading to a macrocycle and to 9,10-dihydro-anthracene derivatives. " ...

In a follow-up communication,26 similar chemistry was used for the production of 2-substituted benzofurans beginning not with an anthranilic acid derivative, but with a resin-bound ortho-hydroxy aryl iodide 3. In the solid-phase work, depicted in Scheme 5, the relevant carboxylic acid was linked to TentaGel via a Mitsunobu reaction, and after deprotection was seen to undergo smooth Heck coupling and cyclization, giving essentially pure compounds in 40-70% overall yield after cleavage. 

Tandem Radical Cyclization/Cross-Coupling or Heck Reactions... 

The first step is to make an indole by Pd(II)-catalysed cyclization in the presence of benzoquinone as reoxidant. The nucleophilic nature of the 3-position of the indole (Chapter 43) was exploited to introduce the required iodine functionality. Rather than direct iodination, a high yielding two-step procedure involving mercuration followed by iodination was employed. The more reactive iodide was then involved in a Heck coupling with an unsaturated side chain in the absence of phosphine... 

Finally, the Heck reaction can be conducted as an intramolecular process where the -hydride elimination after the cyclizing alkene insertion is hampered, resulting in a highly reactive alkyl Pd species. Kim and Ahn [66] have introduced a sequential Heck-cyclization-Suzuki coupling that provides an... 

A wide variety of synthetic processes have been rendered asymmetric through the use of a chiral catalyst. In addition to the types of reaction described above, chiral transition metal catalysts have been used to influence the stereochemical course of isomerization, cyclization, and coupling reactions. As an example, an approach towards the natural product (-)-epibatidine (158) was recently reported by Namyslo and Kaufmann (166). Epibatidine is a potent analgesic and a nicotinic receptor agonist. The synthesis involves an asymmetric Heck-type hydroarylation between the bicyclic alkene (155) and pyridyl iodide (156). A number of bidentate chiral li-... 

Whereas inter- and intramolecular Diels-Alder reactions normally require electron-deficient dienophiles, the 67r-electrocyclization proceeds with a large vaiiety of substituents on a hexatriene. In one such approach, the intramolecular Heck-type reaction of a 2-bromo-1 -en-(ft> — l)-yne 66 is used as a trigger to initiate an intermolecular Heck coupling with an alkene to form the conjugated 1,3,5-hexatriene 67 which eventually cyclizes in a 67T-electrocyclic process (Scheme 3-21) [173]. In many cases, aromatization of the cyclohexadiene 68 formed primarily occurs to yield carbo- and heterobicyclic compounds of type 70 [173a,b]. But with alkyl ethenyl ethers the cyclohexadienes 69 can be obtained in moderate yields [173b]. 

Additional reactions may occur in constitutionally favourable cases Cdomino reactions ), for example, 2-quinolones result from an ordinary Heck coupling, followed by a cyclization step due to nucleophilic attack of the amine at a carboxylic group (eq. (14)) [14e]. Bicyclic nitrogen heterocycles were reported by Buchwald [45]. For a comprehensive review of applications, the reader is referred to the article by de Meijere and Meyer [16 a]. 

Coordinating the triply sulfonated analog, TPPTS, to palladium has led to improvements in CCBF reactions. For example, Genet previously reported the selective intramolecular Heck-type reaction of various substrates to produce the cyclized product in good yield (Eq. 5) intramolecular Heck coupling [18]. One of the most important features of the Pd(TPPTS)3 catalyst involves the regioselectivity associated with the reaction. For these types of reactions, carried out in organic media, the exo product is usually favored. However, with the use of this catalyst, the endo species was the predominant product. 

Heck coupling. An intramolecular H pare 4-methylcoumarin and related com) chiral BINAP to mediate cyclization. an ii 86% ee. ... 

Palladium-catalyzed cro.ss-coupling reactions were also reported. In Smith s synthesis of the lipoprotein-associated phospholipase A2 inhibitor discussed in Section 6.2.2.1, the cyclization precursor 23 was prepared by a Heck coupling between bromopyrimidine 55 and ethyl acrylate to give 56, which was then converted to 23 following conventional procedures <01BMCL701>. Yields were not reported. 

Aryl iodides are more reactive towards oxidative addition than aryl bromides, and a selective Heck coupling (without phosphine ligands) with an unsaturated side chain left the bromide in place. A second Heck reaction of this bromide with an allylic alcohol was used to introduce a second side chain. Cyclization of the amide on to the allylic alcohol was achieved with palladium catalysis, not as might have been expected with palladium(O) but instead with palladium(ll), to produce the seven-membered ring. Finally, the conjugated double bond was reduced and the sulfonamide removed under photolytic conditions. 

However, the substitution pattern on the arene is crucial for the success of the Heck reaction. When a second Heck coupling takes place in an ortho position of another alkenyl unit, cyclization of the intermediately formed o--(/3-arylalkyl)palladium complex may occur, as formation of alkylideneindanes and alkylindenes, especially under classical Heck conditions with phosphines in the catalyst cocktail, was observed (Scheme 2, Table 1). 

Claisen-Schmidt condensation, and acetonylacetone cyclization Aryl coupling reactions (Suzuki, Heck, and Pd-exchanged mesoporous catalysts High activity and reusability avoiding the usual problem of Pd [184]... 

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