Mizoroki intermolecular arylations

An organometallic reaction which shows a close similarity to the Mizoroki-Heck reaction is the cobalt-catalysed [46] reaction between alkenes and organic halides. The use of [CoCKPPhsls] (59) as catalyst for intermolecular arylations of methyl acrylate (1) and styrene (2) was reported by Iyer [47] (Scheme 10.20). The para-substituted aryl iodides could be employed with this homogeneous catalyst, but the more sterically hindered ortho-substituted iodoarenes failed to undergo the desired substitution reaction. Aryl bromides and chlorides, as well as alkyl-substituted halides, proved unreactive under these reaction conditions. 

Scheme 7.15 Ligand-induced enantioselective intermolecular Mizoroki-Heck arylation of 2,3-dihydrolliran.

Figure 7.1 Chiral ligands tested in asymmetric intermolecular Mizoroki-Heck arylations (nd = not determined).

The palladium-catalyzed arylation and alkenylation of olefins, which were first discovered in the 1970 s by Heck (7,2) and Mizoroki (3) and have been often called the "Heck reaction", are versatile synthetic means for making a carbon-carbon bond. These reactions have been extensively used for organic synthesis during the past two decades (4-7). However, no reports on the "asymmetric Heck reaction" have been appeared until very recently. Shibasaki reported an asymmetric intramolecular cyclization of alkenyl iodides to give c/j-decalin derivatives of 80-91% ee (8-10). Overman reported an intramolecular cyclization of alkenyl triflate, giving a chiral quaternary carbon center of 45% ee (77). We report herein the first example of intermolecular asymmetric Heck-type arylation of cyclic olefins catalyzed by (7 )-BINAP-coordinated palladium complexes (Scheme 1) (12,13). 

In 1990, Cabri el al. [40a] reported that the precursor Pd(OAc>2 associated with a biden-tate P P ligand as dppp (1,3-bis-diphenylphosphinopropane) appeared to be more efficient than PPhs in Mizoroki-Heck reactions performed from aryl Inflates and enol ethers (electron-rich alkenes) moreover, the regioselectivity in favour of the a-arylated alkenes was improved to 100%. Since that time, dppp associated with Pd(OAc)2 has been used extensively to catalyse Mizoroki-Heck reactions and to investigate the factors that control the regioselectivity [Ig, 40]. The chiral bidentate (7 )-Binap (2,2 -bis(diphenylphosphino)-1,1-binaphthyl) associated with Pd(OAc)2 has also been used by Shibasaki and coworkers [2b,d,41a] and Overman andPoon [41b] in intramolecular enantioselective Mizoroki-Heck reactions (also, see Link [2f] for an authorative review on the Overman-Shibasaki chemistry), as well as by Hayashi and coworkers [2a, 41c,d] to control the regioselectivity and enantioselectivity of intermolecular Mizoroki-Heck reactions performed from cyclic alkenes (see Schemes 1.3 and 1.2 (Z = O) respectively). 

There are two major realizations of the polar pathway in intermolecular Mizoroki-Heck reactions (1) enantioselective arylation of cyclic alkenes (Chapter 11) and (2) regioselective internal arylation of terminal alkenes (Chapter 3). 

In contrast to intramolecular carbonylative Mizoroki-Heck cyclizations, the intermolecular carbonylative reaction of aryl halides with alkenes has been much less explored. Figure 3.10 depicts one of these rare examples using a carbon monoxide pressure of 5 atm [62], Small... 

Lamaty and coworkers [132] described a nice combination of three palladium-catalysed transformations first, an intermolecular nucleophilic substitution of an allylic bromide to form an aryl ether second, an intramolecular Mizoroki-Heck type transformation in which the intermediate palladium(II) species is intercepted by a phenylboronic acid. Thus, reaction of a mixture of 2-iodophenol (255), methyl 2-bromomethylacrylate (256) and phenylboronic acid in the presence of catalytic amounts of Pd(OAc)2 led to 3,3-disubstituted 2,3-dihydrobenzofuran 257. Besides phenylboronic acid, several substituted boronic acids have also been used in this process (Scheme 8.65). 

Accordingly, catalytic and stoichiometric amounts of cuprous salts were employed for Mizoroki-Heck-type reactions of various conjugated alkenes [ 19]. Intermolecular catalytic arylations of methyl acrylate (1, not shown) and styrene (2) were accomplished under ligand-free conditions using CuBr (3) or Cul (4) as catalyst in A-methyl-2-pyrrolidinone (NMP) as solvent various aryl iodides could be employed (Scheme 10.2). On the contrary, aryl bromides and chlorides, as well as aliphatic halides, were found to be unsuitable substrates. The reactions employing an alkenyl bromide, methylmethacrolein or methyl methacrylate required stoichiometric amounts of copper salts. 

Scheme 10.19 Platinum-catalysed intermolecular Mizoroki-Heck-type arylation of styrene...

As part of comparative studies, Iyer [47] reported the use of Vaska s complex [IrCl(CO)(PPh3)2l (92) in intermolecular Mizoroki-Heck-type reactions of methyl acrylate (1) and styrene (2). Aryl iodides could be used as electrophiles, while bromobenzene, chlorobenzene and aliphatic halides gave no desired product. The catalytic activity was found to be lower than that observed when using Wilkinson s complex [RhCl(PPh3)3] (84). Thus, a higher reaction temperature of 150 °C was mostly required. In contrast to the corresponding cobalt-catalysed reaction, however, Vaska s complex (92) proved applicable to orf/io-substituted aryl iodides (Scheme 10.33). 

The first example of the asymmetric intermolecular Mizoroki-Heck reaction was reported by Hayashi and coworkers [8] in 1991. This involved the asymmetric arylation of 2,3-dihydrofuran (1) with aryl triflates using a palladium/(7 )-BINAP (BINAP = 2,2 -bis(diphenylphosphino)-l,F-binaphthyl) catalytic system (Scheme 11.4). 

While 2,3-dihydrofuran (1) was the initial test substrate of choice for the intermolecular asymmetric Mizoroki-Heck reaction, the reaction was also applied to 2,3-dihydropyrrole 12, which shows similar patterns of both regio- and stereoselectivity to 2,3-dihydrofuran (1) [16], The intermolecular Mizoroki-Heck reaction with substituted 2,3-dihydropynole 12 and aryl triflates 13 gave mixtures of the 2-aryl-2,3-dihyropym)les 14 and the 2-aryl-2,5-dihydropyrroles 15, with the 2,3-product being the major product formed with a 74% ee (Scheme 11.9). 

Shibasaki and coworkers [18] carried out the intermolecular asymmetric Mizoroki-Heck reaction with dihydrodioxepines 20 using the palladium-(50-BlNAP catalytic system (Scheme 11.11). The product 21 was obtained in yields up of to 86% and with up to 75% ee. When the aryl group on the triflate 13 was changed, the enantioselectivity was not found to vary appreciably. 

In general, intermolecular Mizoroki-Heck reactions using immobilized alkenes are not as common as the variant that deals with solid-supported aryl halides, but we will come across another example in Section 14.2,3 on multicomponent Mizoroki-Heck reactions. 

The intermolecular Mizoroki-Heck reaction in macrocyclization of peptides was demonstrated by Byk et al. [207]. The reactions were done out in milligram scale with 15-25% yield. The Pd/C-catalysed Mizoroki-Heck reaction of aryl halides and butyl acrylate performed in an excellent manner. The catalyst could be reused five times without loss of activity [208]. Yields up to 90% could be achieved using bromoarenes and a catalyst loading of 1.5 mol% in a few minutes reaction time. 

Over the course of the past decade, the intermolecular Mizoroki-Heck reaction has witnessed tremendous progress [9,10]. As a comprehensive survey of this area is certainly beyond the scope of this chapter, the decision was taken to include a few important developments, namely the activation of less-reactive aryl chlorides, waste-minimized processes, and novel catalyst systems. 

The final common class of coupling reactions to form C-C bonds described here is the coupling of an aryl halide with an olefin to cleave the C-H bond of the olefin and replace it with an aryl group. This reaction, which is shown generically in Equation 19.18, was first reported by Mizoroki the synthetic utility of this process and e most useful conditions for this process at the time were reported by Heck. ° This process is often called the "Heck reaction," or more appropriately the "Mizoroki-Heck reaction." " The Heck reaction is most commonly conducted with electron-deficient olefins, such as styrene or acrylate derivatives. The electronic properties of these substrates tend to favor formation of the conjugated products. The reaction can also be conducted effectively with ethylene a Heck reaction between 6-methoxy-2-bromonaphthalene and ethylene is one step of a short, catalytic commercial synthesis of naproxen. In contrast, intermolecular reactions of internal olefins typically form mixtures of regioisomeric products. Intramolecular Mizoroki-Heck reactions with intemal olefins are more common. Mizoroki-Heck reactions of aliphatic electrophiles have been reported, but remain rare. Applications of the Mizoroki-Heck reaction have been reviewed. ... 

An intermolecular C-C bond-forming process via C-CN cleavage was also developed. Thus, the Mizoroki-Heck type reaction can proceed by the reaction of aryl cyanides with vinylsilane in the presence of a rhodium catalyst and disilane (Scheme 6.22) [63b]. 

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