Vinyl ethers, Heck coupling

Pd(dba)2 followed by acid hydrolysis gives 8-acetylquinoline <2001T2507>, but utilizing -butyl vinyl ether as coupling partner in a Heck reaction gives 8-acetylquinoline 644 in a better yield. 

Palladium metal catalysts supported on organic resins containing tertiary amino, cyano, carboxyl, and pyridyl groups have been recently investigated in some Heck reactions, such as the coupling of iodobenzene with methyl acrylate and methyl vinyl ether (Scheme 11) [31]. 

Using a different catalytic system, the Larhed group was able to perform regio-selective microwave-promoted chelation-controlled double-/3-arylations of terminal alkenes (Scheme 6.5) [24]. In this Heck approach, the authors used vinyl ethers as chelating alkenes and aryl bromides as coupling partners, employing Herrmann s... 

Equation 11.2 Heck-coupling of 4-tert-butylphenyl triflate and butyl vinyl ether in the presence of water (DPPP = 1,3-bis (diphenyl phosphino) propane). 

Heck s reaction can result in regioisomers, depending on whether the reaction proceeds at the a or (3 carbons in the alkene. A selectivity > 99% to the a-arylation product was achieved in the Heck coupling of 1-bromonaphthalene to butyl vinyl ether in [bmim][BF4], In contrast, the same reaction in toluene, acetonitrile, DMF, or DMSO... 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

Methoxyethenylnitrobenzenes, which are useful as pharmaceutical intermediates, were prepared by application of the Heck coupling reaction between / -bro-monitrobenzene and methyl vinyl ether in the presence of Pd/C, to give 81 % of a mixture of E and Z isomers and 10% p-nitroacetophenone [35]. 

C.i.d. Heck Reaction. 7r-Deflcient chloropyrazines can be Heck-coupled into 1,3-azoles (Scheme 50). It will be recalled that the same methodology was used to couple into the TT-excessive furan, thiophene, and pyrrole heterocycles and their benzo derivatives (vide supra). The Heck reaction in oxazole and thiazole proceeds in a regiospeciflc manner. The new carbon-carbon bond is formed in the 5-position 117 next to the ether heteroatom as commonly observed in vinyl ethers and strongly favored in furan and thiophene. In benzoxazole and benzothiazole the only vacant position is between the two heteroatoms, and the Heck coupling results in substitution into the 2-position 118. " ... 

Figure 3.23 a-Selective Mizoroki-Heck vinylation using vinyl tosylate and mesylate derivatives as coupling partners with enamides and butyl vinyl ether. 

In this regard, it is worth mentioning that PEG of molecular weight <2000, without any additional solvent, has been used as an efficient reaction medium for the coupling of electron-rich and electron-deficient olefins with aryl bromides, providing stereo- and region-selectivities superior to those observed in conventional and ionic liquid solvent systems. The Mizoroki-Heck reaction of p-chlorobromobenzene with -butyl vinyl ether provides the exclusive formation of the (EHonfigurated olefin in 90% yield. 

The oxidative Heck-Mizoroki reaction has also been adapted to flow-chemistry systems. Lahred and coworkers have used this procedure to couple -butyl acrylate and -butyl vinyl ether with arylboronic acids using Pd(OAc)2 with />-benzoquinone as the oxidant [88]. The yields were generally good (56-85%). 

Scheme 4.68 Heck coupling of n-butyl vinyl ether with aryl chlorides...

Cross-coupling Reactions. The allylpalladium chloride dimer (1) has served as an excellent active catalyst precursor for various cross-coupling reactions. The well-known Mizoroki-Heck reaction was widely exemplified in the presence of the system (1)/-Tedicyp (eq 77). Several aryl bromides were reacted with aryl acrylates, styrenyl or alkenyl derivatives, ethyleneglycol vinyl ether, and alk-l-en-3-ol. 8 This catalytic system was efficient for the coupling of vinyl bromides as well. The catalyst loading can be reduced and the substrate/catalyst ratio could reach 100 000 000 in some cases. 

Miura and coworkers reported the first palladium catalyzed intermolecular carbonylative Heck reaction of aryl iodides and five membered olefins in the presence of carbon monoxide (Scheme 1.28) [99]. The expected 2,5-dihydrofuran product was not observed in the carbonylative coupling of 4-iodoanisole and 2,3-dihydrofuran as depicted in Scheme 1.28. Instead, isomerization of the double bond via reinsertion of the palladium(II) hydride followed by another ]S-hydride elimination formed the vinyl ether exclusively. 

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