Decarbonylative Heck

Andrus and Liu exploited a Pd(NHC) decarbonylative Heck coupling reaction in the total synthesis of resveratrol [59], The catalyst was formed in situ with Pd(OAc), and IPr HCl. 

The efficiency of the carbene-based systems has led to their application in total synthesis. For example, Andrus and co-workers [74] recently reported a new synthetic approach to resveratol, the probable causative agent of the French paradox [75]. A decarbonylative Heck reaction was the key step of this concise and cost-effective synthesis [76-78]. 

Scheme 9 Decarbonylative Heck reaction in the synthesis of resveratrol...

Because stoichiometric amounts of base-HX salts are produced in a Heck reaction, alternative sources of aryl groups have been investigated. Carboxylic acid anhydrides were found to react with a PdC2/NaBr catalyst system, where the by-products were CO and a carboxylic acid, p-Nitrophenylbenzoates were also found to be aryl donors in a decarbonylative Heck reaction. An arylation of cinnamates was discovered using Pd(OAc)2 to activate... 

Scheme 8. Synthesis of resverafrol using a direct decarbonylative Heck approach...

Synthesis of polyhydroxylated ester analogues of the stilbene resveratrol was accomplished using decarbonylative Heck couplings [73]. Levulinate- and... 

Goossen, L.J., Paetzold, J. and Winkel, L. (2002) Pd-catalyzed decarbonylative Heck olefination of aromatic carboxylic acids activated in situ with di-tert-butyl dicarbonate. Synlett, 1721-3. 

Goossen, L.J. and Paetzold, J. (2004) Decarbonylative Heck olefination of enol esters salt-free and environmentally friendly access to vinyl arenes. Angew. Chem. Int. Ed., 43,1095-8. 

SCHEME 22.25 Decarbonylative Heck olefination of enol esters. 

Decarbonylative Heck reactions using the corresponding aryl acid chlorides were first employed by Andrus et al. to generate the corresponding fra 5-stilbene derivatives. In a later study, they efficiently prepared fluorinated tra 5-stilbenes (Scheme 5-20). ... 

Scheme 5-20. Decarbonylative Heck reaction with fluorinated aryls. ...

Also neglected have been kinetic studies concerned with comparison of the rates of the decarbonylation of different M(COR)CO systems. Heck 109) reports that at 25 °C MeCOCo(CO)4 dissociates CO about 2250 times more rapidly than MeCOMn(CO)5. This may well be an approximate ratio of the respective rates of the decarbonylation. Qualitative, synthetically oriented experiments seem to indicate that RCOMn(CO)5 decarbonylate faster than their rhenium counterparts (Section V,C). 

Along with these well-defined complexes, other protocols have been developed to directly involve imidazolinm salts with Pd sonrces and form the active catalysts in situ. One of the most popnlar consists of the nse of carbene precursors such as IMes HCl or IPr HCl with PdCOAc) or PdCdba) and a base [40]. A mixture of SIPr HCl and PdCOAc) in a 1 1 ratio was nsed for the synthesis of resveratrol analogues (MOM protected MOM = methoxymethylether) through decarbonylative Mizoroki-Heck coupling [41] (Scheme 6.9). 

The synthetic potential of palladium-mediated cross-coupling reactions (Heck, Suzuki, Stille, Sonogashira, Buchwald-Hartwig) led to the search for a practical synthesis of p-[ F]fluoroiodo- and p-[ F]fluorobromobenzene. p-[ F]Fluoroio-dobenzene (G, X = iodine) can be obtained in poor yield from p F]fluoride and a trimethylammonium precursor (P7). p-p F]Fluorobromobenzene can be prepared in a more reproducible way from 5-bromo-2-nitrobenzaldehyde (radiochemical yields > 70%). The synthesis involves a two-step procedure radiofluorination (F for NO2 substitution), then a catalysed decarbonylation [190,191]. Also very efficient is the one-step reaction of p F]fluoride with a suitable diaryliodonium salt (P6) giving >70% radiochemical yield [192-194]. 

Scheme 2 shows a similar mechanistic pathway for a Heck reaction taking place on a Pd octahedral comer. This mechanism is based on that established for soluble Pd catalysts (ref. 5). Adsorption of the aryl halide (or aryl acid chloride after decarbonylation) gives the aryl Pd halide, 15, by way of the adsorbed intermediate, 14. Vinyl ether adsorption, as in 16, takes place as described in Scheme 1. Aryl insertion gives the halometalalkyl, 17, which on f) elimination to the available 4dxy orbital gives the aryl enol ether, 2 (or 1 depending on which hydrogen is eliminated in 17). The resulting halo palladium hydride, 18, then reacts with the tertiary amine to give the amine hydrochloride and regenerates the octahedral comer for further reaction.

Significant developments have been reported in Heck-type alkylations of alkenes or alkynes. Several reports have addressed the lack of reactivity of aryl chlorides in their reactions with alkenes. Two approaches to this problem have met with success. In the first case, aroyl chlorides are used in place of aryl chlorides under the conditions of reaction, oxidative addition followed by decarbonylation occurs. With activated alkenes, good yields of... 

It would be more interesting and useful if the reaction could be made catalytic. Actually, catalytic decarbonylation reaction was found to be possible by using chlorocarbonylbis(triphenylphosphine) rhodium (XII) (26). This complex is reasonably stable, and more importantly it is four-coordinated and coordinatedly unsaturated, so that it may expand to a six-coordinated complex by the oxidative addition of acyl halides or aldehydes. The oxidative addition of methyl iodide to similar complexes was reported by Heck (5). 

Although aryl halides and triflates are the most commonly used arylating agents, there are successful examples where both aroyl chlorides and arylsulfonyl chlorides have been employed. Pd-catalyzed decarbonylations and desulfonylations and subsequent Heck couplings are often conducted with trialkylamines such as A-ethylmorpholine as a base, but improved yields are reported in cases in which the tertiary amine is replaced by a mixture of potassium carbonate and benzyltrioctylammonium chloride. In Table 2 two examples are given (entries 17 and 18). ... 

Carbonylative, Decarbonylative and Desulfitative Mizoroki-Heck Reactions... 

Figure 4,13 Rhodium-catalysed base-free decarbonylative Mizoroki-Heck reaction.

Figure 4.14 Decarbonylative Mizoroki-Heck reaction of carboxylic anhydrides.

As an alternative to the use of aryl halides as electrophiles, Miura and coworkers [59] employed aroyl chlorides in rhodium-catalysed decarbonylative Mizoroki-Heck-type... 

Scheme 1031 Rhodium-catalysed decarbonylative Mizoroki-Heck-type reaction.

Scheme 7.10 Decarbonylative Mizoroki-Heck arylation of aryl esters.

Scheme 7.12 Salt-free decarbonylative Mizoroki-Heck arylation ofenol esters.

One example of an acylfluoride reduction was reported, although the yield was poor (Scheme 13). In order to minimize the decarbonylation side product trifluoromethylben-zene (7%), the reduction was run with PdX2(Ph3P)2 (X = Cl, Br) under an atmosphere of H2/CO (50-120 40 bar), much as reported by Schoenberg and Heck above. By using polymethylhydrosiloxane (PMHS) as an alternative hydrogen source the reaction was carried out under milder conditions with higher yield. 

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