Alkenes Heck-type reactions

Heck-type reactions 233-41 Heck reaction 233-5 Henry reactions 318-20, 321, 322 meso heterobicyclic alkenes, ring opening of 348-50 heterodonating ligands 9 heterodonor ligands with... 

In aqueous DMF, the reaction can be applied to the formation of C-C bonds in a solid-phase synthesis with resin-bound iodobenzoates (Eq. 6.33).80 The reaction proceeds smoothly and leads to moderate to high yield of product under mild conditions. The optimal conditions involve the use of 9 1 mixture of DMF-water. Parsons investigated the viability of the aqueous Heck reactions under superheated conditions.81 A series of aromatic halides were coupled with styrenes under these conditions. The reaction proceeded to approximately the same degree at 400°C as at 260°C. Some 1,2-substituted alkanes can be used as alkene equivalents for the high-temperature Heck-type reaction in water.82... 

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

The palladium(II)-catalyzed reaction of haloarenes with alkenes and alkynes (Heck-type reactions) in aqueous media has become known only in the preceding few years [Eq. (14)]. 

The palladium-catalyzed Heck-type reaction of methylenecyclopropane 66 in the presence of soft nucleophiles such as sodium diethylmalonate gives a mixture of isomeric alkenes 70 and 71 (Scheme 8.32) [77]. In this process, there is first a carbopalladation of the double bond of 66 giving the cyclopropylcarbinylpalladium in-... 

The Heck-type reaction of vinylic bromides with alkenes in the presence of nucleophiles such as stabilized enolates or secondary amines (morpholine or piperidine) are efficient three-component reactions that were developed in the late 1970s... 

Aliphatic amines can be readily oxidized by Pd(II) to imines or iminium salts and hydrido complexes. The latter can transfer hydrogen to alkenes, leading to the formation of alkanes as byproducts of the Heck reaction (last example, Scheme 8.18). Such reactions can be avoided by using alkali carbonates as base instead of aliphatic amines [148]. Treatment of stannanes or organoboron derivatives with electron-deficient alkenes under acidic reaction conditions can also lead to formal products of Michael addition instead of the products of a Heck-type reaction [149, 150] (Scheme8.19). 

With a combination of organic halide, alkene or alkyne, and palladium catalyst, the reaction may take a superficially similar, but different pathway other than a Heck-type reaction. In these, the halogen is retained in the products, as an alkyl or vinyl halide. These results occur when the starting organic halide is allyl, a- to a carbonyl or similar group, or attached to a perhalogenated carbon atom. In much of the early work, mixtures with Hecklike elimination products were obtained, due to elimination caused by the presence of amine bases in the reaction mixture (equation 165)323. 

Whereas inter- and intramolecular Diels-Alder reactions normally require electron-deficient dienophiles, the 67r-electrocyclization proceeds with a large vaiiety of substituents on a hexatriene. In one such approach, the intramolecular Heck-type reaction of a 2-bromo-1 -en-(ft> — l)-yne 66 is used as a trigger to initiate an intermolecular Heck coupling with an alkene to form the conjugated 1,3,5-hexatriene 67 which eventually cyclizes in a 67T-electrocyclic process (Scheme 3-21) [173]. In many cases, aromatization of the cyclohexadiene 68 formed primarily occurs to yield carbo- and heterobicyclic compounds of type 70 [173a,b]. But with alkyl ethenyl ethers the cyclohexadienes 69 can be obtained in moderate yields [173b]. 

The pioneering studies in this area were reported in 1999 by Narasaka, who demonstrated intramolecular heteroatom Heck-type reactions of 0-pentafluorobenzoyl oximes [97]. As shown below, treatment of unsaturated substrate 97 with a catalytic amount of Pd(PPh,y in the presence of triethyl amine provided pyrrole 98 upon workup with chlorotrimethylsilane. The mechanism of this reaction proceeds via oxidative addition of the N—O bond to afford 99, which undergoes alkene insertion into the Pd—N bond to provide alkyl-palladium complex 100. The exo-methylene product 101 is generated by [i-hydride elimination from 100, and isomerization to the desired pyrrole 98 occurs when chlorotrimethylsilane is added. 

The Pd )-catalyzed reaction of aryl diazonium salts with mono-substituted alkenes [1] was found to be an interesting alternative to the well-known Pd - catalyzed arylhalide alkene coupling (Heck type reaction) or the copper mediated reaction of aryl diazonium salts with alkenes (Meerwein arylation) [2], The reaction can be run without isolation of the diazonium salt in presence of only 0.5 to 1 mol% of the Palladium catalyst in a one pot procedure, in high yield and under nuld conditions. The resulting styrene is reduced in a subsequent hydrogenation step with an in situ generated heterogeneous Pd-catalyst. The combination of three reaction steps without isolation of intermediates and the virtually complete recovery of the Pd-metal at the end of the reaction sequence makes this process [4] extremely efficient. 

Here, the term Heck-type reaction summarizes palladium-catalyzed C—C coupling processes where vinyl or aryl derivatives are functionalized with alkenes, al-kynes, or organometallic reagents (see Eqs. 1 and 2) [1], Aryl and vinyl chlorides are most reluctant to undergo Pd-catalyzed activation, as expected from C—X bond... 

This reaction is applied to a wide range of alkenes such as acrylic esters, styrene, ethylene, 1-alkene, 1,3-dienes, allyl chloride, allyl acetate, and vinyl ethers [122]. Tolerance of the arylmercury compounds to polar functional groups in the substrate renders the reaction applicable to the synthesis of many functionalized styrene derivatives. A ferrocenyl mercury compound undergoes addition to alkene via the Heck type reaction of methyl methacrylate (Eq. 5.29) [123]. 

Silylation of Alkynes and Alkenes. A Heck-type reaction of TMS-I with alkenes in the presence of Pd° and EtsN affords alkenyltrimethylsilanes (eq 26). 

A starting material that is suitable for the direct construction of a heterocycle by an intramolecular Heck-type reaction has to fulfil some simple but fundamental requiranents there has to be the halide function or a triflate for the oxidative addition onto the Pd catalyst, a side chain with an unsaturated functionality such as an alkene or an alkyne in an appropriate distance, and of course the heteroatom in this side chain. Figure 1 presents a substrnctnre typical for very many starting materials, which were transformed to heterocycles by intramolecnlar Heck-type reactions (X = halide, Het = heteroatom). This type of substrnctnre with an allylic side chain is easily accessible by derivatization of 2-bromo- and 2-iodo anilines, phenols, and thiophenols and leads to interesting heterocycles such as indoles and benzofurans, which are related to many natural products and other biological active componnds. 

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. 

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. 

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. 

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]. 

In a related intramolecular rhodium-catalysed Mizoroki-Heck-type reaction of an alkene with an aryl iodide, Wilkinson s catalyst (84) gave significant amounts of side-products due to isomerization of the resulting double bond. In contrast to the corresponding palladium-catalysed transformation, the presence of Et4NCl had no beneficial influence either on the reactivity or on the selectivity [57]. 

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