Heck-Mizoroki coupling

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 first example of an o/t/20-alkylation/Mizoroki-IIcck coupling was reported by Catellani [4] in 1997. Using the PNP dimer as a catalyst in the presence of an aryl halide, norbomene, an alkyl iodide, a terminal olefin and a base at room temperature, 1,2,3-trisubstituted benzenes (Scheme 16), were synthesized through alkylation of a palladacycle of type 35, followed by Mizoroki-Heck coupling with an arylpalladium(II) species of type 36. Although the synthetic scope of the reaction was limited, the importance of the report reveals an unprecedented catalytic transformation where two aryl C-H bonds are converted to sp2-sp3 C-C bonds followed by a standard Mizoroki-Heck coupling. The 1,2,3-trisubstitution pattern generated in the products would be very difficult to obtain via conventional methods. 

While the PNP dimer was an efficient catalyst for the ort/toalkylation/ Mizoroki-Heck reaction, the practicality of the transformation is lessened by the fact that the PNP dimer is not commercially available, and can be quite difficult to prepare. Thus, Catellani adapted the reaction conditions to include commercially available and air-stable Pd(OAc)2 as the catalyst source [46], Under these conditions, the ortho-u kylation/Mizoroki-I Ieck coupling of aryl iodides containing a pre-existing ortho substituent could be carried out. The reaction required higher temperatures, and the addition of KOAc to promote the carbopalladation of norbomene [47] and encourage the o/t/zo-alkylation pathway vs a direct Mizoroki-Heck coupling. 

The above approach of an intermolecular ortho-alkylation followed by an intermolecular Mizoroki-Heck coupling was later extended to heteroaryl iodides by Lautens [48], Using a Pd(OAc)2/triarylphosphine catalyst system, 3-iodothiophene, -benzothiophene, and -indole were transformed to the o/t/zo-alkylation/Mizoroki-Heck coupling products in good to excellent yields (Scheme 17). Unfortunately, 2-iodoheteroaryls were found to be poor substrates for the reaction. 

Scheme 17 Polysubstituted heteroaryls synthesized via ortho-alkylation/Mizoroki-Heck coupling...

Scheme 19 Polycyclic heterocycles synthesized via intramolecular o/t/jo-alkylation/Mizoroki— Heck coupling...

While using o-bromophenol as the ort/w-arylating agent in the above sequence, Catellani found the product to be a 67/-dibenzopyran, the product of an ortho-arylation/Mizoroki-Heck coupling followed by an oxy-Michael addition of the phenol to the electron-deficient alkene. This was later developed into an efficient method for the synthesis of a variety of 6//-dibenzopyrans (Scheme 21) [56, 57], and is one of the most modular and effective methods to construct this interesting heterocyclic framework. 

Scheme 21 fill-1 )ibenzopyrans via o/ffto-Arylaiion/Mizoroki-Heck coupling/oxy-Michael reaction... 

Pd-complexes have also been impregnated on an amorphous silica support vnth the aid of a solution containing [BM IMjlPFej dissolved in tetrahydrofuran and these systems were applied as highly efficient catalysts for promoting Mizoroki-Heck coupling reactions between various aryl halides and cyclohexyl acrylate in alkanes without the presence of additional ligand (Scheme 5.6-8) [105]. 

Scheme 5.6-8 Pd-catalyzed Mizoroki-Heck coupling reactions between aryl halides and cyclohexyl ac7late in alkanes using silica/[BMIM][PF6] supported ionic liquid phase catalysts [105].

The use of a supported palladium complex in the Mizoroki-Heck coupling a phenyl chloride was demonstrated to provide high TON (23 000) and yield (89%) in the reaction with styrene [120]. 

Andrus, M.B., Song, C. and Zhang, J.Q. (2002) Palladium-imidazolium carbene catalyzed Mizoroki-Heck coupling with aryl diazonium ions. Org. Lett., 4, 2079-2. 

C—Cl bond compared with the C—I and C—Br bonds, the chlorides are more reluctant to undergo Mizoroki-Heck reactions [38], There are, however, a number of reports of Mizoroki-Heck couplings where aryl chlorides, as well as even more sluggish tosylates and phosphates, have been utilized [19, 32]. Aryl fluorides are inert under Mizoroki-Heck reaction conditions. 

Figure 3.8 Mizoroki-Heck coupling with 1-tert-butyl vinyl tosylate involving a 1,2-migration of the alkenyl palladium(ll) intermediate.

Figure 3.11 Desulfitative Mizoroki-Heck couplings using arylsulfonyl chlorides.

A relatively recent report on Mizoroki-Heck couplings in telrabutylammonium bromide (TBAB) used 3-hydroxy-methylenealkanoates to give j8-arylketones after a presumed fast decarbomethoxylation (Figure 3.28). Electron-rich and electron-poor aryl bromides were both good substrates. TBAB was found to function better as ionic Uquid than butylpyri-dinium tosylate (which generates a less nucleophiUc anion), most likely due to TBAB s superior capacity to stabilize the catalyst [86], The scope of this reaction was further elucidated in later publications [87,88],... 

In general, the Mizoroki-Heck coupling of aryl halides with both electron-rich and electron-poor terminal alkenes affords monoarylated products. With electron-deficient alkenes under selected reaction conditions, such as with excess of the aryl halide, with special catalysts at high temperatures or under high pressure, a twofold terminal arylation to give 1,1-diarylalkene derivatives may occur (Figure 3.41) [103]. Triple arylations... 

Dubbaka, S.R. and Vogel, P. (2005) Palladium-catalyzed desulfitative Mizoroki-Heck couplings of sulfonyl chlorides with mono- and disubstituted olefins rhodium-catalyzed desulfitative Heck-type reactions under phosphine- and base-free conditions. Chem. Eur. J., 11, 2633-41. 

Orr/zc- em-Dihalovinylanilines 278 were also used in another example of a Buchwald-Hartwig-type/Mizoroki-Heck reaction for the synthesis of 2-vinylic indoles 279 (Scheme 8.69). Lautens and coworkers [140] recently illustrated a domino coupUng under Jeffery s condition where the aniline nitrogen undergoes an amination step followed by a Mizoroki-Heck coupling with various alkenes. In this process, electronic factors and steric hindrance of the different substituents had only a small effect on the yield however, in the formation of 3-substituted indoles using this method only very poor yields were obtained. The procedure can also be performed in an intramolecular mode leading to tricycUc compounds such as pyridino and azepino indoles 281 and 282 (Scheme 8.69). 

Dubbaka, S.R. and Vogel, P. (2005) Palladium-catalyzed desulfltative Mizoroki-Heck coupling of sulfonyl chlorides with mono- and disubstituted olefins rhodium-catalyzed desulfitative Heck-type reactions under phosphine- and base-free conditions. Chem. Eur. J., 11, 2633 1. Kamigata, N., Ozaki, J.-i., and Kobayashi, M. (1985) Reaction of alkenesulfonyl chlorides with olefins catalyzed by a ruthenium(ll) complex. A novel method for synthesis of ( , )- ,4-diaryl-... 

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