Mizoroki—Heck type reaction

Figure 26 Plausible Mizoroki-Heck type reaction pathway with arylboronic acid.

Hiyama and co-workers have reported that the Mizoroki-Heck-type reaction of aryl- and alkenylsilanols is efficiently promoted by a Pd(OAc)2/Cu(OAc)2/LiOAc system (Equation (9)).50 50a in contrast, a dicationic Pd(ll) complex prepared in situ from Pd(dba)2, a diphosphine (dppe or dppben), and Cu(BF4)2 catalyzes 1,4-addition of aryltrialkoxysilanes to a-enones and a-enals in aqueous media (Equation (10)).51 The Pd-catalyzed 1,4-addition of the arylsilanes can be achieved also by using excess amounts of TBAF 3H20, SbCl3, and acetic acid.52... 

A rhodium(l)-catalyzed system in THF is also effective in the Mizoroki-Heck-type reaction of arylsilanediols with acrylates (Scheme 4).53 Interestingly, the use of aqueous THF switches the reaction to 1,4-addition forming /3-arylated esters. The proposed catalytic cycles for these reactions involve 1,4-addition of an arylrhodium species to an acrylate. The change of the reaction pathway is probably because, in aqueous THF, the resultant Rh enolate 6 undergoes protonolysis rather than /3-elimination. Similar Rh-catalyzed 1,4-additions to a,/3-unsaturated carbonyl compounds have been achieved with arylsilicones,54 arylchlorosilanes,55 and aryltrialkoxysilanes.56,57 The use of a cationic Rh-binap complex leads to highly enantioselective 1,4-additions of alkenyl- and arylsilanes.58 583... 

Iridium complexes as well as [Rh(OH)(cod)]2 can catalyze the Mizoroki-Heck-type reaction of arylsilanediols with acrylates. Aryltrialkoxysilanes activated by TBAF also work as the aryl donor in the presence of H20. In contrast to the Rh-catalyzed reaction, this reaction does not form / -arylated saturated esters even in aqueous media.69... 

Hiyama and Mori introduced the Mizoroki-Heck-type reaction of aryl- and vinyl-... 

C-0 bond cleavage of aryl triflates or tosylates is also studied in relation to Mizoroki-Heck type reactions [101], Oxidative addition of PhOTf to Pd(PPh3)4 is 10 times slower than that of Phi. Since similar trend is observed for the catalytic Mizoroki-Heck reaction, the oxidative addition of aryl compound is considered to be the rate-determining step in the overall catalytic process. This feature suggests that the C-0 bond cleavage of aryl triflate proceeds by the concerted SNAr mechanism. However, since the triflate normally acts as a non-coordinating anion, thermally unstable cationic arylpalladium(II) complexes are formed in this reaction (Scheme 3.54). 

Based on a transformation described by Catellani and coworkers [80], Lautens s group [81] developed a series of syntheses of carbocycles and heterocycles from aryl iodide, alkyl halides and Mizoroki-Heck acceptors. In an early example, the authors described a three-component domino reaction catalysed by palladium for the synthesis of benzo-annulated oxacycles 144 (Scheme 8.37). To do so, they used an m-iodoaryl iodoalkyl ether 143, an alkene substimted with an electron-withdrawing group, such as t-butyl acrylate and an iodoalkane such as -BuI in the presence of norbomene. It is proposed that, after the oxidative addition of the aryliodide, a Mizoroki-Heck-type reaction with nor-bornene and a C—H activation first takes place to form a palladacycle PdCl, which is then alkylated with the iodoalkane (Scheme 8.37). A second C—H activation occurs and then, via the formation of the oxacycle OCl, norbomene is eliminated. Finally, the aryl-palladium species obtained reacts with the acrylate. The alkylation step of palladacycles of the type PdCl and PdCl was studied in more detail by Echavarren and coworkers [82] using computational methods. They concluded that, after a C—H activation, the formation of a C(sp )—C(sp ) bond between the palladacycle PdCl and an iodoalkane presumably proceeds by oxidative addition to form a palladium(IV) species to give PdC2. This stays, in contrast with the reaction between a C(sp )—X electrophile (vinyl or aromatic halide) and PdCl, to form a new C(sp )—C(sp ) bond which takes place through a transmetallation. 

Edmondson et al. [138] developed a synthesis of 2,3-disubstituted indoles using an am-ination as the first step (Scheme 8.67). The reaction of 264 and 265 with catalytic amounts of Pd2(dba)3 and the ligand 268 gave compound 267 in high yield. To get to the final indole, a second charge of palladium had to be added after 12 h, otherwise only the amination product was isolated. It can be assumed that in the first step the enaminone 266 is formed, which then cyclizes in a Mizoroki-Heck-type reaction to give 267. In a similar way, reaction of 264 and 269 led to 270 by an acyl migration in the Mizoroki-Heck cyclization product. 

Palladium(II)-Catalysed Transformations Involving a Mizoroki-Heck-Type Reaction... 

In the synthesis of the steroid (+)-equilenin (302) Nemoto et al. [153] also used a palladium(II)-catalysed domino process which includes a ring expansion followed by a Mizoroki-Heck-type reaction (Scheme 8.74). Interestingly, almost complete reversion of... 

Herein, a survey of the literature up to mid 2007 is provided, covering catalytic arylation and alkenylation reactions of alkenes with metals other than palladium. The review summarizes Mizoroki-Heck-type reactions employing organic (pseudo)halides as electrophiles (Scheme 10.1), while oxidative Mizoroki-Heck-type reactions [6] are beyond the scope of this review (Chapters 4 and 9). Valuable transition-metal-catalysed arylation reactions of alkenes employing stoichiometric amounts of organometallic compounds as... 

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. 

Additionally, an intramolecular Mizoroki-Heck-type reaction catalysed by Cul (4) was reported (Scheme 10.3) [19]. 

Scheme 10.3 Copper-catalysed intramolecular Mizoroki-Heck-type reaction.

While this ligand-free copper-catalysed Mizoroki-Heck-type reaction required relatively high temperatures of 150 °C [19], the use of DABCO (9) as ligand allowed for significantly milder reaction conditions [20]. Thereby, satisfying isolated yields were even achieved for orf/jo-substituted electron-rich aryl iodides and alkenyl bromides (Scheme 10.4). However, aryl bromides, particularly electron-rich ones, were converted only sluggishly. 

The long reaction times required for the previously reported copper-catalysed Mizoroki-Heck-type reactions could be significantly reduced with microwave irradiation [21] in polyethylene glycol (PEG) as solvent [22]. An induction period [23] was noted, resulting, interestingly, in improved isolated yields for the reused catalytic system in the second cycle (Scheme 10.5) [22]. Various aryl iodides, including orr/io-substituted electrophiles, were efficiently converted within 30 min. On the contrary, Ijromo- and chlorobenzene could not be converted under these reaction conditions. 

A heterogeneous arylation of ethyl acrylates and styrene (2) was successfully catalysed by CU/AI2O3 (15). This catalytic system proved applicable to aryl iodides with both electron-withdrawing and -donating substituents [24]. Subsequently, a silica-supported poly-y-aminopropylsilane Cu(II) complex was used for Mizoroki-Heck-type reactions of three aryl iodides with methyl acrylate (1), acrylic acid (16) and styrene (2) [23, 25]. 

Nickel-Catalysed Mizoroki-Heck-Type Reactions... 

Generally applicable nickel-catalysed arylation reactions of alkenes were accomplished through the use of relatively strong stoichiometric reducing reagents [29]. Hence, Perichon and coworkers [30] developed an electrochemical, highly selective nickel-catalysed Mizoroki-Heck-type reaction (Scheme 10.8). Importantly, this early report showed that not only aryl iodides and bromides, but also less reactive aryl chlorides could be used for luckel-catalysed Mizoroki-Heck-type reactions. 

Scheme 10.6 Copper-catalysed Mizoroki-Heck-type reaction in an ionic liquid.

The use of pyridine (31) as additive allowed for more selective and efficient nickel-catalysed arylations of styrenes (Scheme 10.10) [32, 33]. Aryl and alkyl bromides gave good yields of isolated products. With respect to the latter, secondary alkyl bromides proved superior to primary ones. However, use of methyl acrylate (1) as substrate yielded predominantly products originating from conjugate additions, rather than Mizoroki-Heck-type reactions. 

Scheme 10.9 Nickel-catalysed MIzoroki-Heck-type reaction with stoichiometric amounts of Zn (27).

Scheme 10.12 Nickel(0) phosphite complex37as catalyst for Mizoroki-Heck-type reactions.

Scheme 10.13 In situ generated nickel arbene complex for a Mizoroki-Heck-type reaction with aryl bromide 41.

Scheme 10.14 Pincer-type nickel(ll) complex 45 for Mizoroki-Heck-type reactions with aryl chlorides.

Scheme 10.16 Nickel-catalysed Mizoroki-Heck-type reactions with TPPTS (53) as ligand.

Cobalt-catalysed electrochemical arylation reactions of acrylates were achieved by Gosmini and coworkers. The presence of 2,2 -bipyridine (Bpy, 63) was found crucial to reduce the formation of conjugate addition products in this transformation. Notably, this Mizoroki-Heck-type reaction proved applicable to aryl iodides and bromides and to an alkenyl chloride (Scheme 10.22) [48]. 

A heterogeneous cobalt catalyst was employed for arylations of styrene (2) and two acrylates with aryl iodides. Generally, isolated yields were significantly lower than those observed for heterogeneous nickel catalysts [24]. Further, a silica-supported poly-y-aminopropylsilane cobalt(II) complex was reported as a highly active and stereoselective catalyst for Mizoroki-Heck-type reactions of styrene (2) and acrylic acid (16) using aryl iodides [23,25]. 

Recently, cobalt hollow nanospheres were successfully used in stereoselective Mizoroki-Heck-type reactions of acrylates with aryl bromides and iodides [49]. The recyclable catalyst was most efficient when using NMP and K2CO3 as solvent and base respectively (Scheme 10.23). 

An early example for cobalt-catalysed Mizoroki-Heck-type reactions with aliphatic halides by Branchaud and Detlefsen showed that an intermolecular substitution of styrene (2) could be achieved with [Co(dmgH)2py] (70) (dmgH = dimethylglyoxime monoanion) as catalyst in the presence of visible light. This radical reaction led selechvely to the substitution products when using stoichiometric amounts of Zn (27) and pyridine (31) as additives (Scheme 10.24) [52]. 

A more efficient and more generahy applicable cobalt-catalysed Mizoroki-Heck-type reaction with aliphatic halides was elegantly developed by Oshima and coworkers. A catalytic system comprising C0CI2 (62), l,6-bis(diphenylphosphino)hexane (dpph 73)) and Mc3 SiCH2MgCl (74) allowed for intermolecular subshtution reactions of alkenes with primary, secondary and tertiary alkyl hahdes (Scheme 10.25) [51, 53]. The protocol was subsequently applied to a cobalt-catalysed synthesis of homocinnamyl alcohols starting from epoxides and styrene (2) [54]. 

The catalytic system proved not only applicable to alkyl hahdes, but also allowed for the intramolecular conversion of aryl halides. Interestingly, the corresponding Mizoroki-Heck-type cyclization products were formed selectively, without traces of reduced side-products (Scheme 10.27) [55]. Therefore, a radical reaction via a single electron-transfer process was generally disregarded for cobalt-catalysed Mizoroki-Heck-type reactions of aromatic hahdes. Instead, a mechanism based on oxidative addition to yield an aryl-cobalt complex was suggested [51]. 

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