Mizoroki-Heck alkenylations

In a seminal communication, Chiusoh et al. reported an example of an intercepted Mizoroki-Heck reaction for the first time [86]. A palladiumreducing agent, ammonium formate, produced a mixture of 146 and 147 in a reaction temperature-dependent ratio (Scheme 7.34). The minor product 147 was formed by standard intermolecular Mizoroki-Heck alkenylation and subsequent reductive cleavage of the intermediate C(sp )—Pd" bond formation of the major product 146 involved an additional intramolecular alkene insertion prior to the reduction step. 

The Mizoroki-Heck reaction is a metal catalysed transformation that involves the reaction of a non-functionalised olefin with an aryl or alkenyl group to yield a more substituted aUcene [11,12]. The reaction mechanism is described as a sequence of oxidative addition of the catalytic active species to an aryl halide, coordination of the alkene and migratory insertion, P-hydride elimination, and final reductive elimination of the hydride, facilitated by a base, to regenerate the active species and complete the catalytic cycle (Scheme 6.5). 

Silver salts are also employed to create more effective chiral catalysts by exchange of counter anions. For example, in the Mizoroki-Heck reaction of alkenyl or aryl halides, silver salts are employed to form effective chiral Pd intermediates by abstracting a halide group from the Pd11 precursor species (Scheme 53).227,228... 

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... 

Alkenyl, Alkynyl, Aryl and Heteroaryl Acids. Treatment of readily accessible (E)- and (Z)-alkyl and aryl substituted vinyl boronates (196) with triethyl phosphite in the presence of lead diacetate results in their stereospecific transformation into (E)- and (Z)-vinylphosphonates (197) (Scheme 53). ° Palladium acetate catalysed Mizoroki-Heck reaction of arylboronic acids (198) with diethyl vinylphosphonates (199) is an effective synthetic approach to... 

In the Mizoroki-Heck process, aryl and alkenyl halides are converted on reaction with olefins in the presence of a base into arylated or alkenylated olefins. The arylation case is shown in the scheme but it is applicable also to the alkenylation process. 

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

A number of intramolecular Mizoroki-Heck reactions yield the product consistent with a formal a r/-elimination of the HPdX [11], These experimental findings are in opposition to the generally accepted mechanism of a 5y -elimination however, a reasonable explanation is at hand in most cases. There are two main types of alkenyl derivatives which, if added to an CT-aryl- or cr-alkenylpalladium(II) complex, deliver the formal a ft-elimination product. The first case is intramolecular Mizoroki-Heck reactions with o ,jS-unsaturated carbonyl systems which result in the product of a formal 1,4-addition. The initially formed <7-(y3-aryl)- or <7-(/3-alkenyl)alkylpalladium complex should be long-lived enough to epimerize through a palladium(II) enolate intermediate and, thus, deliver the formal anr/-elimination product through conventional 5yn-elimination (Scheme 6.2). 

Barluenga et al. [87] developed a one-pot synthesis for indoles from o-bromoanilines and alkenyl bromides via a cascade alkenyl amination/Mizoroki-Heck reaction. In order to improve the yields of their procedure, they studied the cyclization of preformed imine 113 to indole 114 in the presence of DavePhos and X-Phos as supporting ligands (Scheme 6.30). 

Jeffery has reported an alternative additive-based solution to yield Hy-abstracted products. Mizoroki-Heck reaction of allylic alcohols with aryl or alkenyl hahdes in the presence of silver salts (AgOAc or Ag2C03) results in selective Hy -abstraction [7]. Similar hydroxy-coordination to the cationic organopalladium intermediates are believed to be involved in this system. In this regard, the use of hypervalent iodonium salts is also effective for generating cationic palladium species [8]. 

Figure 7.14 Chelation-assisted Mizoroki-Heck reaction of alkenyl(2-pyridyl)silanes.

Figure 7,18 Mizoroki-Heck reaction of alkenyl sulfoxides promoted by o-aminophenyl group.

The o-aminophenyl-directed asymmetric Mizoroki-Heck reaction can also be applied to intramolecular reactions [30]. For example, when alkenyl iodide 63 is subjected to palladium catalyst, Mizoroki-Heck cyclization furnishes 64 with almost complete diastereose-lectivity (Figure 7.21). An asymmetric reaction utihzing an enantiomerically pure sulfoxide unit is also possible. 

One distinguishes palladium(0)- and palladium(ll)-catalysed reactions. The most common palladium(O) transformations are the Mizoroki-Heck and the cross-coupling transformations such as the Suzuki-Miyaura, the Stille and the Sonogashira reactions, which allow the arylation or alkenylation of C=C double bonds, boronic acid derivates, stan-nanes and alkynes respectively [2]. Another important palladium(O) transformation is the nucleophilic substitution of usually allylic acetates or carbonates known as the Tsuji-Trost reaction [3]. The most versatile palladium(ll)-catalysed transformation is the Wacker oxidation, which is industrially used for the synthesis of acetaldehyde from ethylene [4]. It should be noted that many of these palladium-catalysed transformations can also be performed in an enantioselective way [5]. 

In most of the palladium-catalysed domino processes known so far, the Mizoroki-Heck reaction - the palladium(0)-catalysed reaction of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - has been apphed as the starting transformation accordingly to our classification (Table 8.1). It has been combined with another Mizoroki-Heck reaction [6] or a cross-coupling reaction [7], such as Suzuki, Stille or Sonogashira reactions. In other examples, a Tsuji-Trost reaction [8], a carbonylation, a pericyclic or an aldol reaction has been employed as the second step. On the other hand, cross-couphng reactions have also been used as the first step followed by, for example, a Mizoroki-Heck reaction or Tsuji-Trost reactions, palladation of alkynes or allenes [9], carbonylations [10], aminations [11] or palladium(II)-catalysedWacker-type reactions [12] were employed as the first step. A novel illustrative example of the latter procedure is the efficient enantioselective synthesis of vitamin E [13]. 

In another interesting example by Grigg and Sridharan [45], the reaction of the alkynyl aryl iodide 71 with norbomene in the presence of Pd(OAc)2, triphenylphosphine and triethylamine led to the cyclopropanated norbomene derivate 75 as a single diasteieomer in 40% yield. It can be assumed that, first, the alkenyl palladium species 72 is formed stereoselectively, which undergoes a Mizoroki-Heck reaction with norbomene to give 73 in a jy -fashion followed by formation of the cyclopropanated intermediate 74, which loses HPdl (Scheme 8.17). 

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. 

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. 

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]. 

An early report on rhodium-catalysed Mizoroki-Heck-type arylations of alkene 20 using two alkenyl bromides was disclosed by Chiusoli et al [28], Thus, catalytic amounts of [RhCl(PPh3)3] (84) allowed for conversion of potassium 3-butenoate (20) (Scheme 10.28), a substrate that can potentially direct the rhodium catalyst through coordination of its carboxylate group. 

In an intramolecular Mizoroki-Heck-type alkenylation of alkenes, Wilkinson s catalyst [RhCl(PPh3)3] (84) proved superior than other rhodium compounds (Scheme 10.29) [56]. Notably, the selectivities of the cyclization of various 2-bromo-1,6-dienes were found to be improved with Wilkinson s catalyst when compared with those observed with palladium complexes. Thereby, the corresponding l,2-bis(methylene)cyclopentanes, which themselves are valuable substrates for further cycloaddition reactions, such as 1,3-diene 86, could be isolated in high yields. 

The standard Mizoroki-Heck reaction is the substitution of a vinylic hydrogen by an alkenyl or aryl group catalysed by palladium(O) complexes (Scheme 11.1). Since its discovery in 1968 by Heck [1-3], this elaboration of substituted alkenes by direct C-C bond formation at the vinylic carbon centre has evolved into a synthetic transformation whose potential has only recently been exploited in the key steps of many total syntheses (Chapter 16) [4]. This recent exploitation has been due to a better understanding of the proper choice of reactants, solvent, base, additives, catalyst precursor and ligands necessary for optimal reaction conditions. 

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