Heck reaction stereospecificity

Heck reactions can be carried out in the absence of phosphine ligands.141 These conditions usually involve Pd(OAc)2 as a catalyst, along with a base and a phase transfer salt such as tetra-n-butylammonium bromide. These conditions were originally applied to stereospecific coupling of vinyl iodides with ethyl acrylate and methyl vinyl ketone. 

The main steps in the currently accepted catalytic cycle of the Heck reaction are oxidative addition, carbopalla-dation (G=G insertion), and / -hydride elimination. It is well established that both, the insertion as well as the elimination step, are m-stereospecific. Only in some cases has formal /r/ / i--elimination been observed. For example, exposure of the l,3-dibromo-4-(dihydronaphthyloxy)benzene derivative 16 and an alkene 1-R to a palladium source in the presence of a base led to a sequential intra-intermolecular twofold Heck reaction furnishing the alkenylated tetracyclic products 17 in good to excellent yields (Scheme 9). " In the rate-determining step, the base removes a proton in an antiperiplanar orientation from the benzylic palladium intermediate. The best amine base was found to be l,4-diazabicyclo[2.2.2]octane, which apparently has an optimal shape for this proton abstraction. 

Since 1,4 addition of a variety of appropriate aryl caibanions to 36 failed, an intramolecular version of the Heck reaction was examined. With this end in view, the ketone 36 was reduced stereospecifically to the corresponding allyl alcohol which was then protected as its p-methoxybenzyl ether 37. The amine, obtained on reduction of the azide 37, was condensed with 6-bromopiperonylic acid to furnish the amide 38. 

Whereas the intermolecular Heck reaction is limited to unhindered alkenes, the intramolecular version permits the participation of even hindered substituted alkenes, and many cyclic compounds can be prepared by the intramolecular Heck reaction [37]. The stereospecific synthesis of an A ring synthon of la-hydroxyvitamin D has been carried out. Cyclization of the (7T)-alkene 88 gives the (fT)-exo-diene 90, and the (Z)-alkene 91 affords the (Z)-exo-diene 92 [38]. These reactions are stereospecific, and can be understood by cis carbopalladation to form 89 and the. sun-elimination mechanism. 

A haloalkene that contains a stereogenic C=C double bond can usually be coupled with alkenes via the Heck reaction without isomerization. This is illustrated with the three reaction pairs in Figure 16.36. As can be seen, both the as- and the /raw-configured iodoalkenes react with acrolein or methyl vinyl ketone or acrylic acid methyl ester with complete retention of the C=C double bond configuration. These coupling reactions are thus stereoselective and— when considered as a pair—stereospecific. 

Alkenyl, Alkynyl, Aryl and Heteroaryl Acids. Treatment of readily accessible (E)- and (Z)-alkyl and aryl substituted vinyl boronates (196) with triethyl phosphite in the presence of lead diacetate results in their stereospecific transformation into (E)- and (Z)-vinylphosphonates (197) (Scheme 53). ° Palladium acetate catalysed Mizoroki-Heck reaction of arylboronic acids (198) with diethyl vinylphosphonates (199) is an effective synthetic approach to... 

When the alkene is cyclic, or the insertion step forms a quaternary center, a substitution product is not obtained. For example, stereospecific syn addition of an arylpalladium halide 13 to cyclohexene generates cyclohexylpalladium(II) intermediate 14 (Scheme 6-3). The C—Pd cr-bond in this intermediate is anti to H and syn elimination to form a substitution product is not possible. However, elimination of cis hydrogen H is possible and generates allylic product 15. This pathway of the Heck reaction is particularly important in complex molecule construction since a new stereogenic center is produced. 

Heck reaction. The Heck reaction has been conducted in superheated steam (260°). ( /Z)-Isomers of 3-aryl-3-phenylpropenoates can be synthesized stereospecifically by the Heck method. 

The role of the IL is crucial in both the PdNP formation and stereospecifity of C—C coupling that could not be obtained in previous studies of PdNP-catalyzed Heck reactions [33e-g]. Salts of N-butyronitrile pyridinium cation react with PdCl2 to give dinitrile complexes that turn black upon addition of phenyltributyktan-nane, and the PdNPs formed catalyze Stille and Suzuki C—C coupling reactions. 

The Pd(0) complex may be generated in situ from a Pd(II) salt and two equivalents of a phosphine, or used in, a preformed state, such as Pd(PPh3)4, with an amine added to the reaction mixture to effect dehydrohalogenation and regenerate the Pd(0) species. In general, the Heck reaction is stereospecific with retention of the halide geometry, and bromides show higher stereospecificity than iodides. The best yields are obtained with electron-deficient... 

C.ii.e. Heck Reaction The cross-coupling between 5-iodoimidazoles and methyl acrylate has been appUed to complex structures as depicted for the preparation of (E S-(2-carbomethoxyvinyl)-l-(2,3,5-lri-0-acetyl-i eM-Z)-ribofuranosyl)imidazole-4-carboxamide 142 from the corresponding 5-iodoimidazole (Scheme 59). Acrylonitrile reacts in the same manner under Heck conditions to provide the ( )-5-cyanovinyl derivative. The C-glycosyl bond formation in the Heck coupling between the 3-iodopyrazolo[4,3-dlpyrimidine 143 and the ribofuranoid glycal 144 was regio- and stereospecific. The iodo substituent in the substrate was introduced by a simple electrophilic substitution. ... 

DiazC,AlzateD,RodriguezR,OchoaC,Sierra CA. High yield and stereospecific synthesis of segmented poly(p-phenylene vinylene) by the Heck reaction. Synth Met 2013 172 32-6. 

In addition, the Heck reaction is completely stereospecific with regard to the haloalkene the configuration of the double bond in the haloalkene is preserved. 

Fig. 16.36. Stereoselectivity and stereospecificity of Heck coupling reactions with isomeric iodoalkenes.

Later, Heck also reported the synthesis of amide from various aryl, heterocyclic, and vinylic halides and primary or secondary amines in the presence of a palladium catalyst.The reaction was carried out under an atmosphere of carbon monoxide, and a tertiary amine was generally added to neutralize the hydrogen halide formed in the reaction. The reaction is also highly stereospecific with cis- and trans-winyl halides (Table 3). 

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