Alkene complexes nucleophilic addition

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

Carbonylation reactions have been observed using both Pd(II)-alkene complexes and CT-bonded Pd(II) species formed by oxidative addition. Under reductive conditions, the double bond can be hydrocarbonylated, resulting in the formation of a carboxylic acid or ester.238 In nucleophilic solvents, the intermediate formed by solvopalladation is intercepted by carbonylation and addition of nucleophilic solvent. In both types of reactions, regioisomeric products are possible. 

A.2. Solvocarbonylation. In solvocarbonylation, a substituent is introduced by a nucleophilic addition to a tt complex of the alkene. The acylpalladium intermediate is then captured by a nucleophilic solvent such as an alcohol. A catalytic process that involves Cu(II) reoxidizes Pd(0) to the Pd(II) state.244... 

As mentioned already, new methylidene-group IV metal complexes have been prepared and were subsequently used in nucleophilic additions to carbonyl electrophiles (Scheme 43).53 In contrast to titanium and zirconium, the reaction of methylidene hafnium dichloride 97 benzophenone stopped at the first stage (i.e., addition). The tertiary alcohol was obtained in 73% yield, while the corresponding alkene was formed only as minor product. 

The carbon-metal cr-bond emanating from the addition of an alcohol nucleophile to a 7t-alkene complex may undergo a protonolytic cleavage to effect overall hydroalkoxylation of the alkene. While this process is difficult to achieve due to the propensity of the cr-metal species to undergo f3-H elimination, some encouraging progress in this area has recently been forthcoming. 

Co-ordination of an alkene to an electronegative metal (often it may carry a positive charge) activates the alkene toward attack of nucleophiles. After the nucleophilic attack the alkene complex has been converted into a c-bonded alkyl complex with the nucleophile at the (3-position. With respect to the alkene (in the "organic" terminology) the alkene has undergone anti addition of M and the nucleophile Nu, see Figure 2.25. 

The reaction starts with an oxidative addition of an allylic compound to palladium(O) and a Tt-allyl-palladium complex forms. Carboxylates, allyl halides, etc. can be used. In practice one often starts with divalent palladium sources, which require in situ reduction. This reduction can take place in several ways, it may involve the alkene, the nucleophile, or the phosphine ligand added. One can start from zerovalent palladium complexes, but very stable palladium(O) complexes may also require an incubation period. Good starting materials are the 7t-allyl-palladium intermediates ... 

A a-5-bonded r-alkene (r] ) intermediate (325) has been invoked to account for the hydrogenation of the thiaplatinacycle (324) to the complex (326) in which two hydrogens have been added and a hydrogen shift has occurred." When coordinated to neutral and cationic palladium(II) and platinum(II) centres, the diphosphine 2,3-bis(diphenylphosphino)propene, on treatment with benzylamine, was found to undergo isomerization to coordinated c/i-l,2-bis(diphenylphosphino)propene rather than the expected nucleophilic addition to the double bond. 

Because the addition steps are generally fast and consequently exothermic chain steps, their transition states should occur early on the reaction coordinate and therefore resemble the starting alkene. This was recently confirmed by ab initio calculations for the attack at ethylene by methyl radicals and fluorene atoms. The relative stability of the adduct radicals therefore should have little influence on reacti-vity 2 ). The analysis of reactivity and regioselectivity for radical addition reactions, however, is even more complex, because polar effects seem to have an important influence. It has been known for some time that electronegative radicals X-prefer to react with ordinary alkenes while nucleophilic alkyl or acyl radicals rather attack electron deficient olefins e.g., cyano or carbonyl substituted olefins The best known example for this behavior is copolymerization This view was supported by different MO-calculation procedures and in particular by the successful FMO-treatment of the regioselectivity and relative reactivity of additions of radicals to a series of alkenes An excellent review of most of the more recent experimental data and their interpretation was published recently by Tedder and... 

As an alternative to addition of anionic nucleophiles followed by reoxidation, rhodium(l)-catalyzed C-H activation allowed the nucleophilic addition of alkenes to the intermediate Rh(i) carbene complex <2002JA13964, 2004JOC7329>. Purine behaved anomalously compared to other heterocycles, for which selective monoalkylation was observed, and underwent sequential substitution first at C-8 and then at C-6 (Equation 8). Caffeine was monoalkylated at C-8 in low yield (15%). Selectivity for C-8-arylation was also observed in the palladium-catalyzed C-H activation of 6-phenyl-9-benzylpurine (aryl iodides, 0.05 equiv Pd(OAc)2, 3 equiv Cul, 2.5 equiv CS2CO3, DMF, 160 °C, 60 h, 48-95% yields) <2006OL5389>. 

Most of the reactions listed in Table 6 involve prior activation of the substrate by coordination to palladium in the form of a v-, a 77-ally lie, a 77-benzylic, or an alkyl or aryl complex. Once coordinated to the metal, the substrate becomes an electron acceptor and can react with a variety of different nucleophiles. The addition of nucleophiles (Nu) to the coordinated substrate may occur in two different ways, as shown by Scheme 9 for 7r-alkene complexes 397"399 (a) external attack leading to trans addition of palladium and nucleophile across the 77-system (path A) or (b) internal addition of the coordinated nucleophile to the complexed alkene resulting in cis addition of palladium and nucleophile to the double bond. The cis and trans adducts (120) and (121) may then undergo /3-hydride elimination (/3-H), producing the vinylic oxidation product... 

Backwall and coworkers have extensively studied the stereochemistry of nucleophilic additions on 7r-alkenic and ir-allylic palladium(II) complexes. They concluded that nucleophiles which preferentially undergo a trans external attack are hard bases such as amines, water, alcohols, acetate and stabilized carbanions such as /3-diketonates. In contrast, soft bases are nonstabilized carbanions such as methyl or phenyl groups and undergo a cis internal nucleophilic attack at the coordinated substrate.398,399 The pseudocyclic alkylperoxypalladation procedure occurring in the ketonization of terminal alkenes by [RCC PdOOBu1], complexes (see Section 61.3.2.2.2)42 belongs to internal cis addition processes, as well as the oxidation of complexed alkenes by coordinated nitro ligands (vide in/ra).396,397... 

Palladium(II) salts, in the form of organic solvent soluble complexes such as PdCl2(RCN)2, Pd(OAc>2 or Li2PdCU, are by far the most extensively utilized transition metal complexes to activate simple (unactivated) alkenes towards nucleophilic attack (Scheme 1). Alkenes rapidly and reversibly complex to pal-ladium(II) species in solution, readily generating alkenepalladium(II) species (1) in situ. Terminal monoalkenes are most strongly complexed, followed by internal cis and trans (respectively) alkenes. Geminally disubstituted, trisubstituted and tetrasubstituted alkenes are only weakly bound, if at all, and intermolecular nucleophilic additions to these alkenes are rare. 

One of the earliest uses of palladium(II) salts to activate alkenes towards additions with oxygen nucleophiles is the industrially important Wacker process, wherein ethylene is oxidized to acetaldehyde using a palladium(II) chloride catalyst system in aqueous solution under an oxygen atmosphere with cop-per(II) chloride as a co-oxidant.1,2 The key step in this process is nucleophilic addition of water to the palladium(II)-complexed ethylene. As expected from the regioselectivity of palladium(II)-assisted addition of nucleophiles to alkenes, simple terminal alkenes are efficiently converted to methyl ketones rather than aldehydes under Wacker conditions. 

As noted in the introduction, in contrast to attack by nucleophiles, attack of electrophiles on saturated alkene-, polyene- or polyenyl-metal complexes creates special problems in that normally unstable 16-electron, unsaturated species are formed. To be isolated, these species must be stabilized by intramolecular coordination or via intermolecular addition of a ligand. Nevertheless, as illustrated in this chapter, reactions of significant synthetic utility can be developed with attention to these points. It is likely that this area will see considerable development in the future. In addition to refinement of electrophilic reactions of metal-diene complexes, synthetic applications may evolve from the coupling of carbon electrophiles with electron-rich transition metal complexes of alkenes, alkynes and polyenes, as well as allyl- and dienyl-metal complexes. Sequential addition of electrophiles followed by nucleophiles is also viable to rapidly assemble complex structures. 

Reactions of alkenes and alkynes that generate a carbon-metal bond by nucleophilic addition to a metal ir-complex and subsequently undergo carbon monoxide insertion to yield a carbonyl product are... 

Nucleophilic additions to alkenes 293 Nucleophilic vinylic substitution (SNV) Reactions 298 Nucleophilic substitution of Fischer carbene complexes 303 Reactions involving carbocations 309 Miscellaneous reactions 312... 

Other reactions for which a discussion of their structure-reactivity behavior in terms of the PNS has provided valuable insights include nucleophilic addition and substitution reactions on electrophilic alkenes, vinylic compounds, and Fischer carbene complexes reactions involving carbocations and some radical reactions. 

Very recently, an intramolecular version with alkynyl [3-diketones or (3-diketoe-sters has been reported (Scheme 10.23).42 With such substrates, the reaction required a mixture of silver tetrafluoroborate and copper triflate as catalysts. Here, also, nucleophilic addition of a ketoenol to a n complex seemed responsible for an exo-dig cyclization, but depending on substituents, exocyclic or endocyclic alkenes were obtained. 

The chiral anisole derivative 37 has been used in the synthesis of several asymmetric functionalized cyclohexenes (Table 9) [22]. In a reaction sequence similar to that employed with racemic anisole complexes, 37 adds an electrophile and a nucleophile across C4 and C3, respectively, to form the cyclohexadiene complex 38. The vinyl ether group of 38 can then be reduced by the tandem addition of a proton and hydride to C2 and Cl, respectively, affording the alkene complex 39. Direct oxidation of 39 liberates cydohexenes 40 and 41, in which the initial asymmetric auxiliary is still intact. Alternatively, the auxiliary may be cleaved under acidic conditions to afford /y3 -allyl complexes, which can be regioselectively attacked by another nucleophile at Cl. Oxidative decomplexation liberates the cyclohexenes 42-44. HPLC analysis revealed high ee values for the organic products isolated both with and without the initial asymmetric group. 

In Fig. 4.35 the nucleophile depicted is anionic, but Nu may also be a neutral nucleophile, such as an amine or H2O. There are many alkene complexes of middle and late transition elements which undergo this type of reaction, e.g. M = Pd2+, Pt2, Hg2+, Zn2+, FeCp(CO)2+. The addition reaction of this type is the key step in the Wacker-type processes catalyzed by palladium. 

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