Heck vinylations

Retrosynthetic path e in Scheme 2.2 requires a regioselective oxidation of an o-nitrostyrene to the corresponding phenylacetaldehyde. This transformation has been accomplished hy Wacker oxidation carried out in such a way as to ensure the desired regioselectivity. The required o-nitrostyrenes can be prepared by Heck vinylation. One procedure for oxidation uses 1,3-propaiiediol to trap the product as a l,3-dioxane[15]. These can then be hydrogenated over Rh/C and cyclized by treatment with dilute HCl,... 

Scheme 14 Microwave-promoted Heck vinylation of 3-bromo-2-quinolones 3.4.3...

Heck vinylation 22 Heck vs. Diels-Alder 278 Heck-Mizoroki reaction 194 Heterocycles, benzocondensed 246, 249, 252... 

A regiocontrolled Heck vinylation [7] of commercially available 2-hydroxyethyl vinyl ether 7 in dry DM SO has been reported (Scheme 8.4). Flash heating by micro-... 

Bis(pyrazolyl)borate copper complex 47 has been employed as a catalyst in the homogeneous and heterogeneous styrene epoxidation reactions <00JCS(CC)1653>. Pyrazole palladacycles 48 have proven to be stable and efficient catalysts for Heck vinylations of aryl iodides <00JCS(CC)2053>. An asymmetric borane reduction of ketones catalyzed by N-hydroxyalkyl-/-menthopyrazoles has been reported <00JHC983>. 

Herrmann WA, Brossmer C, Reisinger CP, Riermaier T, Ofele K, Beller M (1997) Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions. Part 10. Palladacycles efficient new catalysts for the Heck vinylation of aryl halides. Chem Eur J 3 1357-1364 Iyer S, Jayanthi A (2001) Acetylferrocenyloxime palladacycle-catalyzed Heck reactions. Tetrahedron Lett 42 7877-7878 Iyer S, Ramesh C (2000) Aryl-Pd covalently bonded palladacycles, novel amino and oxime catalysts di- x-chlorobis(benzaldehydeoxime-6-C,AT)dipalla-dium(II), di- x-chlorobis(dimethylbenzylamine-6-C,A)dipalladium(II) for the Heck reaction. Tetrahedron Lett 41 8981-8984 Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun 1287-1289 (b) idem,... 

In a related approach, Murakami synthesized clavicipitic acid and costaclavine [79], and later extended this chemistry to a synthesis of chanoclavine-I featuring the intramolecular Heck vinylation 240 to 241 [266], The corresponding enone failed to cyclize under these conditions. Noteworthy is that radical cyclizations, which often compete successfully with Heck reactions, were poor in this system. 

It is mentioned in an early paper on the effect of water on Heck vinylations [62] that 2,4-dimethoxy-5-iodopyrimidine reacted with 1-(ethoxyethenyl)-tri-n-butylstannane to afford an acylated pyrimidine derivative in 83 % yield (via in situ hydrolysis of the intermediate enol ether) (Scheme 6.28). 

Bienayme and Yezeguelian [63] described a new synthesis of retinal via a Heck vinylation of a C15 tertiary allylic alcohol with a C5 iodoacetal. Thus, the bromo acetal was prepared by a known procedure [64], by a bromination-dehydrobromination reaction sequence (E and Z isomers 40/60). 

When the Heck vinylic arylation reaction is carried out with an olefin which is either a gas or a low boiling liquid, it must be run in a pressure vessel. Depending upon the product desired, the olefin is usually present in an excess concentration in order to insure formation of vinyl substituted products. In the case of the reaction of ethylene with 2 the stoichiometry of the reactants is critical (Fig. 5). If 4-bromobenzocyclobutene 2 is present in higher concentrations than ethylene, a different monomer, l,2-di(4-benzocyclobutenyl)-ethylene 11 is obtained. 

However, it has turned out that there are a few synthetic methods having broad scope, that is, (a) for the synthesis of dioxepins and dithiepins (i) transacetalization of the corresponding diol or dithiol, respectively, with an open chain acetal (ii) treatment of the corresponding diol or dithiol with sodium borohydride and reaction of the resulting dianion with a gem-dihalogen derivative. The latter method is particularly useful for the synthesis of dioxepins and dithiepins unsubstituted in the 2-position (b) for the synthesis of 4,5-dihydro-l,3-dioxepins (i) metal- or base-catalyzed double-bond isomerization and (ii) Heck vinylation or arylation, respectively, for the synthesis of 6-substituted 4,5-dihydro-l,3-dioxepins. 

Heck vinylation Pd(OAc)2/ TPPTS Enhanced activity Bhanage et al. (1999b)... 

Scheme 11 Chelation-controlled terminal Heck vinylation of an enol ether...

The inter- and intramolecular Heck reactions provide other routes to substituted pyridines . Although electron-deficient 2-bromopyridines are resistant to substitution under Heck conditions, the aminopyridine 142 affords a high yield of the adduct 143 (Equation 68) <1998T6311>. The intermolecular Heck reaction of a 3-pyridyltriflate with ethyl acrylate is accelerated by LiCl <1999SL804>. An efficient Heck vinylation of 3-substituted-2-bromo-6-methylpyridines with methyl acrylate has been developed <2005T4569>. 

Bauerle and coworkers [38] suggested and applied Pd-catalyzed cross-coupling reactions of 3 -bromocoumarin derivatives for the generation of coumarin libraries with a highly diverse substitution pattern. In the case of 3-bromocoumarin (18), the reaction conditions for combinatorial Heck vinylations with alkenes 19, Suzu-... 

R. F. Heck, Vinyl Substitutions with Oiganopalladium Intermediates, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 4, 833, Peigamon Press, Oxford, U. K., 1991. 

The palladacycle 29 is either prone to reductive elimination, furnishing the minor by-product 26, or to an oxidative addition of an alkyl iodide, giving rise to an octahedral Pd(IV) species 30. Reductive elimination places the alkyl substituent in the ortho position and another CH activation furnishes the palladacycle 31. Again, an octahedral Pd(IV) intermediate 32 is obtained after an oxidative addition of an alkyl iodide. As before, reductive elimination occurs and gives an alkyl-Pd intermediate 33 that sets the stage for a jd-elimination and expulsion of norbornene. Now, the resulting ortho, ortho double alkylated aryl Pd intermediate 34 reacts with the terminal olefin and finally concludes the sequence with a Heck vinylation to give the final product 27. 

Intramolecular allylic substitutions in an exo-fashion are perfectly appropriate for cyclizations with concomitant generation of a vinyl group that sets the stage for a Heck vinylations. Poli and his group [82] have recently presented a sequence where methylene active malonamide esters with an al-... 

A Pd(0)-catalyzed Claisen rearrangement with a subsequent intramolecular Heck vinylation has been demonstrated by Watson and coworkers [84], Upon treatment with Pd(PPh3)4 the allyl vinyl ether undergoes a Pd(0)-catalyzed 1,3 oxygen to carbon allyl shift to afford an a-allyl ketone that... 

Here, the order of coupling can be nicely illustrated upon varying the stoichiometry of the aryl halide and the reaction conditions. The amination proceeds faster and at lower temperatures than the Heck reaction, as shown by symmetrical N,N-diarylation at 60 °C followed by the Heck vinylations of a second aryl halide at 110 °C to give the amino stilbene derivatives 109 (Scheme 38). 

Ionic liquids can be used as replacements for many volatile conventional solvents in chemical processes see Table A-14 in the Appendix. Because of their extraordinary properties, room temperature ionic liquids have already found application as solvents for many synthetic and catalytic reactions, for example nucleophilic substitution reactions [899], Diels-Alder cycloaddition reactions [900, 901], Friedel-Crafts alkylation and acylation reactions [902, 903], as well as palladium-catalyzed Heck vinylations of haloarenes [904]. They are also solvents of choice for homogeneous transition metal complex catalyzed hydrogenation, isomerization, and hydroformylation [905], as well as dimerization and oligomerization reactions of alkenes [906, 907]. The ions of liquid salts are often poorly coordinating, which prevents deactivation of the catalysts. 

Figure 1 Regioselectivity in Heck vinylation reactions arrows show the site of C-C bond formation...

One general approach takes advantage of the Hydrobora-tion of aUcynes to give vtnylboron componndsd As shown in equation (6), Heck vinylation occurs using a variety of aryl-boron reagents. " ... 

Aryl bromides as well as aryl chlorides show increased reactivity in the Mizo-roki-Heck vinylation (eq. (3)) with various olefins when the reaction is performed in molten ammonium or phosphonium salts [28] (see also Section 3.1.6). Many common catalysts, including ligand-free Pd salts, show a substantial inerease in activity and thermal stability. 

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