Additions oxidative

Oxidative addition (OA) and its reverse-reaction counterpart, reductive elimination (RE), play important roles as key steps in catalytic cycles (see Chapter 9) and in synthetic transformations (see Chapter 12). In the broadest sense, OA involves the attachment of two groups X-Y to a metal complex of relatively low oxidation state. This produces a new complex with an oxidation state two units higher than before, an increase in coordination number of two, and an electron count two higher than present in the starting material. Equation 7.24 outlines the essential changes present in an OA (and, of course, in the reverse direction, RE). 

Oxidative additions typically occur on transition metal complexes with counts of 16 electrons or fewer. Addition is possible to 18-electron complexes however, loss of a ligand (dissociation) must occur first (equation 7.26).55 

A binuclear variant of OA may occur where each metal increases in oxidation state by one unit. Equation 7.27 shows one such example.56 

Finally, OA may occur intramolecularly, as equation 7.28 demonstrates. Intramolecular additions of this type are called cyclometallations or, more specifically, an orthometallation in the case shown. 

56It should be pointed out that in equation 7.27 the metal undergoes oxidation, but the coordination number of the metal does not change. 

Oxidative Addition. Oxidative addition is a reaction type which has been very much studied in organometallic chemistry for approximately 25 years [71]. This type of reaction requires by definition the increase of the coordination number and of the oxidation number of the metal. It can take place therefore mainly in the group of planar complexes of metals with d8-configuration  

Thermally activated oxidative addition [43,49] (TOA), in the class of compounds which is considered here, has been observed [39,56] especially for the pair Pt(II)/Pt(IV), where it occurs with all Pt(CAN)2 compounds and with the bis-heteroleptic Pt(CAN)(C AN ) complexes. Generally, it can be stated that alkyl-iodides and some alkyl-bromides add in TOA reactions, whereas most other organic halides require photochemically activated oxidative addition (POA). The differences of the steric course in these reactions have already been discussed above. The most extensive series of reactions have been studied with Pt(tpy)2 as the Pt(II) compound [72]. 

There are several recent reports of TOA reactions, which could give rise to complexes of interest in photochemistry and photophysics. One is the intramolecular TOA [73] of a Pt(II) complex according to the following scheme  

The reaction leading to the new Pt(II) complex in the case X = F, H, proceeds probably through a sequence of oxidative addition and subsequent reductive elimination. The same sequence gives C-C bond formation in intermolecular oxidative addition reactions (TOA) with Pd(II) complexes [40]. The corresponding POA leads to complete dissociation of the C-bonded ligand (see below). 

Oxidative addition reactions are very important in organometallic synthesis. Oxidative addition involves  

Addition of O2 to give an q -peroxo complex is related to reaction type 24.35. Each addition in equations 24.34-24.36 occurs at a 16-electron metal centre, taking it to an 18-electron centre in the product. Most commonly, the precursor has ad or d configuration, e.g. Rh(I), Ir(I), Pd(0), Pd(II), Pt(0), Pt(II), and the metal must have an accessible higher oxidation state, e.g. Rh(III). If the starting compound contains an 18-electron metal centre, oxidative addition cannot occur without loss of a 2-electron ligand as in reaction 24.37. 

Many examples of the addition of small molecules (e.g. H2, HX, RX) are known. The reverse of oxidative addition is reductive elimination, e.g. reaction 24.38, in which an acyl substituent is converted to an aldehyde. 

Oxidative addition initially gives a cw-addition product, but ligand rearrangements can occur and the isolated product may contain the added groups mutually cis or trans. 

The reaction is also called CO insertion since the incoming CO molecule seems to have been inserted into the Mn—Cmc bond this name is misleading. If reaction 24.39 is carried out using CO, none of the incoming CO ends up in the acyl group or in the position trans to the acyl group the isolated product is 24.45. 

Oxidative addition is an addition reaction that occurs on a metal and raises its oxidation state (Ecj. 12.15). The reaction is similar to that of an insertion (discussed in Section 10.11), and it expands the coordination sphere of the metal. A number of mechanisms for oxidative addition exist, and which one occurs is a function of the metal and the adding group. Although experimental studies of these reactions have been performed on many different kinds of complexes, we only examine a few prototypical examples here. 

CHAPTER 12 ORGANOTRANSITION METAL REACTION MECHANISMS AND CATALYSIS 

Other reactants, however, give trans products. The oxidative addition of methyl iodide or acetylbromide to fraus-Ir(CO)(PPh2Me)2Cl results in a trans arrangement of the groups that added to the metal (Eqs. 12.18 and 12.19). Therefore, there must be different mechanisms for the addition of different organic structures. 

Orbital interactions that describe the oxidative addition of H2. 

The oxidative addition has been most extensively studied on iridium complexes, particularly Vaska s complex. The latter is a square planar complex, frans-L2lrCl(CO), with a d8 electron count containing iridium(I). After the oxidative addition we formally obtain iridium(III), an octahedral complex, with a d6 electron configuration i.e. the 16-electron square-planar complex is converted into an octahedral 18-electron complex. In Fig. 4.26 we have depicted the oxidative addition of methyl iodide to Vaska s complex (L = phosphine) [39]. A large 

In general, oxidative addition reactions occur at mononuclear complexes as discussed above. Oxidative addition of dihydrogen often occurs at binuclear complexes. The reaction of dicobalt octacarbonyl may illustrate this  

The oxidative addition of acids is another instructive example. It resembles the reactions with alkyl halides and may result in another amphoteric hydride  

The starting material is an 18-electron nickel(O) complex which is protonated forming a divalent five-coordinate nickel hydride [41]. This can react further with alkenes to give alkyl groups, but it can also react as an acid with hard bases to regenerate the nickel(O) complex. Similar oxidative addition reactions have been recorded for phenols, water, amines, carboxylic acids, mineral acids (e.g. HCN), etc. 

Intermolecular oxidative additions involving C-H bond breaking is a topic which has been extensively studied recently. It is usually referred to as C-H activation the idea is that the M-H and M-hydrocarbyl bonds formed will be much more prone to functionalization than the unreactive C-H bond [42-44], Intramolecular oxidative additions of C-H bonds have been known for quite some time [45] (see Fig. 4.27). This process is termed orthometallation. It occurs frequently in metal complexes, and is not restricted to ortho protons. It has considerable importance in metal-mediated synthesis. 

In an oxidative addition reaction a compound XY adds to a metal complex during which the XY bond is broken and two new bonds are formed, MX and MY. X and Y are reduced, and both will have a minus one charge (formally at least) and hence the formal oxidation state of the metal is raised by two. The co-ordination number of the metal also increases by two. While the electron 

Electronic ligand effects are highly predictable in oxidative addition reactions a-donors strongly promote the formation of high-valence states and thus oxidative additions, e.g. alkylphosphines. Likewise, complexation of halides to palladium(O) increases the electron density and facilitates oxidative addition [11], Phosphites and carbon monoxide, on the other hand, reduce the electron density on the metal and thus the oxidative addition is slower or may not occur at all, because the equilibrium shifts from the high to the low oxidation state. In section 2.5 more details will be disclosed. 

The oxidative addition of alkyl halides can proceed in different ways, although the result is usually atrans addition independent of the mechanism. In certain cases the reaction proceeds as an SN2 reaction as in organic chemistry. That is to say that the electron-rich metal nucleophile attacks the carbon atom of the alkyl halide, the halide being the leaving group. This process leads to inversion of the stereochemistry of the carbon atom (only when the carbon atom is asymmetric can this be observed). There are also examples in which racemisation occurs. This has been explained on the basis of a radical chain 

In general, oxidative addition reactions of clusters are identified with dissociative chemisorption of heterogeneous solid-state catalysts. Therefore, studies of oxidative addition of clusters are useful in finding connections between these areas of chemistry. In the case of clusters, oxidative addition may be one-center if both fragments of the XY molecule add to the same metal atom or two-center if X and Y are coordinated to two 

Oxidative addition of hydrogen [reactions (3.55)-(3.57)] to clusters may change the multiplicity of M — M bonds, or cause their breaking. Most often, however, this process is accompanied by dissociation of a Lewis base and, in such cases, of course, the skeleton of the cluster does not change. Oxidative addition and reductive elimination of trinuclear ruthenium clusters have been investigated. Based on the kinetic equation, activation parameters, and isotope effects, the pathway for the reversible reaction 

Bond breaking involving the vinyl C—H rather than alkyl C—H bond shows that the influence of several metal atoms creates unique ligand chemistry in clusters which differs from the chemistry of mononuclear complexes see scheme (3.92). 

For cyclic olefins, compounds possessing structure (B) with a carbon-carbon double bond parallel to one of the M —M bonds are formed. Ruthenium carbonyls in analogous reactions give both (A) and (B) forms, as does Os3(CO)i2 in the reaction 

ligands coordinated through N, O, P, etc. undergo oxidative addition to give a, or 7 metallation products [see structures (3.94)]. 

These reactions, as the name suggests, involve an increase in both the formal oxidation state and the coordination number of the metal. Oxidative addition (OA) reactions are among the most important of organometallic reactions and are essential steps in many catalytic processes. The reverse type of reaction, designated reductive elimination (RE), is also very important. These reactions can be described schematically by the equation  

For example, heating Fe(CO)5 in the presence of I2 leads to formation of c/5-l2Fe(CO)4. The reaction has two steps  

The first step involves dissociation of CO to give a 4-coordinate iron(O) intermediate. In the second step, iron is formally oxidized to iron(II) and the coordination number expanded by the addition of two iodo ligands. This second step is an example of oxidative addition. Like most oxidative additions, this step involves an increase by 2 in both the oxidation state and coordination number of the metal. 

NHC species is remarkably general. Like the formation of the [(NHC)AgX] species itself, subsequent reaction with transition metal precursors can be carried out in air without rigorous purification of solvents, with some exceptions. In an interesting application, Crabtree and co-workers used sequential additions of two different silver NHC reagents in order to synthesize iridium complexes of the formula [(NHC )(NHC )Ir(COD)].  

The direct oxidative addition of the C2-H to electron-rich late transition metals is another method for the preparation of NHC-metal complexes. Mild bases can also promote this reaction. Considering the large difference in between the imidazolium ion and the weak bases such as triethylamine or metal carbonates that are employed, it is likely that the base serves to deprotonate the oxidatively added imidazolium ion driving the reaction forwards.  

Cavell also reported the oxidative addition of imidazolium salts to coordi-natively unsaturated bis-IMes complexes of Pd and Ni (Equation (3.1)). Reactions occurred cleanly, generating tris-NHC metal hydrides, which were remarkably stable to reductive elimination, likely due to the steric constraints of NHCs, which prevent the orbital overlap between the hydride and the car-bene carbon required for reductive elimination. 

Fiirstner et al. demonstrated that oxidative addition of C2-C1 imidazolium ions to Pd(PPti3)4] generated mixed phosphine-NHC complexes. Baker described the interesting C-C oxidative addition reaction of diimida-zolium ion 8 to [Pd(PPh3)4] yielding the bis-NHC cyclophane complex 9 (Equation (3.2)).  

In recent years, ionic liquids have become extremely popular as a green alternative to conventional reaction solvents.Since a number of the most popular ionic liquids used are A, A -dialkylated imidazolium salts, their true role in transition metal catalysed reactions, particularly in the presence of base, must be scrutinized. Following the initial report of a successful Heck reaction performed in an ionic liquid by Earle and co-workers,Xiao and co-workers were able to isolate a number of isomeric [(NHC)2PdBr2] complexes from the reaction mixture (Equation (3.3)). Under stoichiometric conditions, heating [Pd(OAc)2] and NaOAc in the ionic liquid, [BMIM]Br, the dimeric palladium carbene complex, [(IBuMe)PdBr2]2 could be readily obtained, which, upon further heating, generated bis-NHC-Pd complexes. 

This process is similar to the formation of Grignard reagents 4 from alkyl halides and Mg(0). In the preparation of Grignard reagents, Mg(0) is oxidized to Mg(II) by the oxidative addition of alkyl halides to form two covalent bonds. 

Oxidative addition is facilitated by higher electron density of the metals and, in general, n-donor ligands such as R3P and H attached to M facilitate oxidative addition. On the other hand, 7c-accepter ligands such as CO and alkenes tend to suppress oxidative addition. 

A number of different polar and nonpolar covalent bonds are capable of undergoing the oxidative addition to M( ). The widely known substrates are C—X (X = halogen and pseudohalogen). Most frequently observed is the oxidative addition of organic halides of sp2 carbons, and the rate of addition decreases in the order C—I C—Br C—Cl C—F. Alkenyl halides, aryl halides, pseudohalides, acyl halides and sulfonyl halides undergo oxidative addition (eq. 2.1). 

The following compounds with H—C and II—M bonds undergo oxidative addition to form metal hydrides. This is examplified by the reaction of 6, which is often called ortho-metallation, and occurs on the aromatic C—H bond at the ortho position of such donar atoms as N, S, 0 and P. Reactions of terminal alkynes and aldehydes are known to start by the oxidative addition of their C—H bonds. Some reactions of carboxylic acids and active methylene compounds are explained as starting with oxidative addition of their O—H and C—H bonds. 

Metal-metal bonds M —M such as R2B—BR2 and R3Si—SiR3 undergo oxidative addition, (where M represents main group metals eq. 2.2). 

Although 16-electron three-membered zirconacycles are generally unsuitable for X-ray analysis, their complexes with phosphines, such as PMe3, or some ethers, such as THF, have often yielded crystalline compounds suitable for X-ray analysis. Thus, their existence and identity have been firmly established. 

The substitution of a CO ligand by another 2-electron donor (e.g. PR3) may occur by photochemical or thermal activation, either by direct reaction of the metal carbonyl and incoming ligand, or by first replacing a CO by a more labile ligand such as THF or MeCN. An example of the latter is the formation of Mo(CO)5(PPh3) (equation 23.25) which is most efl ectively carried out by first making the THF adduct (23.34) in situ. 

In reaction 23.27, the incoming ligand provides 4 electrons and displaces two CO ligands. Multiple substitution by 

It should be noted that sometimes different terms are used for the same process. This situation arises from the fact that chemical terms specific to organometallic chemistry originate from inorganic chemistry, and these terms differ from the ones originating from organic chemistry. 

The oxidative addition occurs with coordinatively unsaturated complexes. As a typical example, the saturated Pd(0) complex, Pd(PPh3)4 (four-coordinate, 18 electrons) undergoes reversible dissociation in situ in a solution to give the unsaturated 14-electron species Pd(PPh3)2, which is capable of undergoing oxidative addition. Various a-bonded Pd complexes are formed by oxidative addition. In many cases, dissociation of ligands to supply vacant coordination sites is the first step of catalytic reactions. 

It should be pointed out that some Pd-catalyzed reactions of alkyl halides, and even alkyl chlorides are emerging, indicating that facile oxidative addition of alkyl halides is occurring. 

Hydrogen ligands on transition metals, formed by oxidative additions, are traditionally, and exclusively, called hydrides , whether they display any hydridic behavior or not. Thus Pd(0) is oxidized to H-Pd(II)-H by the oxidative addition 

On the other hand, cross-coupling reactions involving organic halides initially had the important limitation that only aryl bromides and iodides could be employed. However, as aryl chlorides are more profusely available and, in general, less expensive 

Recently, direct C-H arylation [50-54] has emerged as an elegant and effective alternative to C-C cross-coupling reactions since these reactions do not require the presence of the organometallic nucleophile and provide only HX associated to a base as by-product. Therefore, these reactions are very interesting both in terms of atom-economy and the relative toxicity of the wastes. 

In the following sections, a brief description of the three elementary steps of the catalytic cycle (Fig. 1.3) will be presented separately. More specifically, some of the most relevant studies reported in the last years on these steps will be reviewed. 

The opposite reaction to the oxidative addition is the reductive elimination, where the A-B molecule is expelled from the [M(A)(B)] complex. In principle, these reactions can be reversible but, in practice, they tend to evolve in either one or other direction. In fact, the position of equilibrium in any particular case depends on the overall thermodynamics, which in turn depends on the relative stability of the metal in each oxidation state and the strength of the A-B bond with respect to the M-A and M-B bonds. On the basis of these dependences and other chemical concepts (e.g. coordination number of the metal), we can consider the following series of trends as a guide for predicting the reactivity of metal complexes towards oxidative addition  

Probably, one of the best features of oxidative addition reactions is the unusual wide range of reagents A-B that can be involved. These can be divided into three groups (i) species that are non-polar or have low polarity (e.g. H2, silanes) (ii) reagents that are highly polar (e.g. alkyl halides, strong acids) and (Hi) reagents that are intermediate in polarity (e.g. amines, alcohols). A direct consequence derived 

---

Vaska s compound, tri7rt5-[Ir(CO)(Ph3P)2Cl]. Undergoes ready oxidative addition to give Ir(IlI) complexes. 

W C, A Tempcz)rrk, R C Hawley and T Hendrickson 1990. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. Journal of the American Chemical Society 112 6127-6129. ensson M, S Humbel, R D J Froese, T Matsubara, S Sieber and K Morokuma 1996. ONIOM A Multilayered Integrated MO + MM Method for Geometry Optimisations and Single Point Energy Predictions. A Test for Diels-Alder Reactions and Pt(P(t-Bu)3)2 + H2 Oxidative Addition. Journal of Physical Chemistry 100 19357-19363. 

Organic compounds M—R and hydrides M—H of main group metals such as Mg, Zn, B, Al, Sn, SI, and Hg react with A—Pd—X complexes formed by oxidative addition, and an organic group or hydride is transferred to Pd by exchange reaction of X with R or H. In other words, the alkylation of Pd takes place (eq. 9). A driving force of the reaction, which is called transmetallation, is ascribed to the difference in the electronegativities of two metals. A typical example is the phenylation of phenylpalladium iodide with phenyltributyltin to form diphenylpalladium (16). 

The most useful reaction of Pd is a catalytic reaction, which can be carried out with only a small amount of expensive Pd compounds. The catalytic cycle for the Pd(0) catalyst, which is understood by the combination of the aforementioned reactions, is possible by reductive elimination to generate Pd(0), The Pd(0) thus generated undergoes oxidative addition and starts another catalytic cycle. A Pd(0) catalytic species is also regenerated by /3-elimination to form Pd—H which is followed by the insertion of the alkene to start the new catalytic cycle. These relationships can be expressed as shown. 

As a typical example, the catalytic reaction of iodobenzene with methyl acrylate to afford methyl cinnamate (18) is explained by the sequences illustrated for the oxidative addition, insertion, and /3-elimination reactions. 

The reactions of the second class are carried out by the reaction of oxidized forms[l] of alkenes and aromatic compounds (typically their halides) with Pd(0) complexes, and the reactions proceed catalytically. The oxidative addition of alkenyl and aryl halides to Pd(0) generates Pd(II)—C a-hondi (27 and 28), which undergo several further transformations. 

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

TT-Aliylpalladium chloride reacts with a soft carbon nucleophile such as mal-onate and acetoacetate in DMSO as a coordinating solvent, and facile carbon-carbon bond formation takes place[l2,265], This reaction constitutes the basis of both stoichiometric and catalytic 7r-allylpalladium chemistry. Depending on the way in which 7r-allylpalladium complexes are prepared, the reaction becomes stoichiometric or catalytic. Preparation of the 7r-allylpalladium complexes 298 by the oxidative addition of Pd(0) to various allylic compounds (esters, carbonates etc.), and their reactions with nucleophiles, are catalytic, because Pd(0) is regenerated after the reaction with the nucleophile, and reacts again with allylic compounds. These catalytic reactions are treated in Chapter 4, Section 2. On the other hand, the preparation of the 7r-allyl complexes 299 from alkenes requires Pd(II) salts. The subsequent reaction with the nucleophile forms Pd(0). The whole process consumes Pd(ll), and ends as a stoichiometric process, because the in situ reoxidation of Pd(0) is hardly attainable. These stoichiometric reactions are treated in this section. 

Several Pd(0) complexes are effective catalysts of a variety of reactions, and these catalytic reactions are particularly useful because they are catalytic without adding other oxidants and proceed with catalytic amounts of expensive Pd compounds. These reactions are treated in this chapter. Among many substrates used for the catalytic reactions, organic halides and allylic esters are two of the most widely used, and they undergo facile oxidative additions to Pd(0) to form complexes which have o-Pd—C bonds. These intermediate complexes undergo several different transformations. Regeneration of Pd(0) species in the final step makes the reaction catalytic. These reactions of organic halides except allylic halides are treated in Section 1 and the reactions of various allylic compounds are surveyed in Section 2. Catalytic reactions of dienes, alkynes. and alkenes are treated in other sections. These reactions offer unique methods for carbon-carbon bond formation, which are impossible by other means. 

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

Facile oxidative addition is possible with iodides and bromides. The reactions of iodides can be carried out even in the absence of a phosphine ligand,... 

Aromatic acyl halides and sulfonyl halides undergo oxidative addition, followed by facile elimination of CO and SO2 to form arylpalladium complexes. Benzenediazonium salts are the most reactive source of arylpalladium complexes. 

Oxidative addition of alkyl halides to Pd(0) is slow. Furthermore, alkyl-Pd complexes, formed by the oxidative addition of alkyl halides, undergo facile elimination of /3-hydrogen and the reaction stops at this stage without undergoing insertion or transmetallation. Although not many examples are available, alkynyl iodides react with Pd(0) to form alkynylpalladium complexes. 

Success of the reactions depends considerably on the substrates and reaction Conditions. Rate enhancement in the coupling reaction was observed under high pressure (10 kbar)[l 1[. The oxidative addition of aryl halides to Pd(0) is a highly disfavored step when powerful electron donors such as OH and NHt reside on aromatic rings. Iodides react smoothly even in the absence of a... 

Stereochemical features in the oxidative addition and the elimination of /3-hydrogen of cyclic and acyclic alkenes are different. The insertion (palladation) is syn addition. The syn addition (carbopalladation) of R—Pd—X to an acyclic alkene is followed by the syn elimination of 3-hydrogen to give the trans-a ksne 6, because free rotation of 5 is possible with the acyclic alkene. On the other hand, no rotation of the intermediate 7 is possible with a cyclic alkene and the syn elimination of /3-hydrogen gives the allylic compound 8 rather than a substituted alkene. 

Three-component coupling with vinylstannane. norbornene (80). and bro-mobenzene affords the product 91 via oxidative addition, insertion, transme-tallation, and reductive elimination[85]. Asymmetric multipoint control in the formation of 94 and 95 in a ratio of 10 1 was achieved by diastereo-differ-entiative assembly of norbornene (80), the (5 )-(Z)-3-siloxyvinyl iodide 92 and the alkyne 93, showing that the control of four chiralities in 94 is possible by use of the single chirality of the iodide 92. The double bond in 92 should be Z no selectivity was observed with E form[86]. 

Oxidative addition of the sulfonyl chlorides 144 is followed by facile generation of SO2 to form arylpalladium complexes which undergo alkene inser-tion[112,113]. 

The alkynyl iodide 150 undergoes the oxidative addition to form an alky-nylpalladium iodide, and subsequent insertion of an alkene gives the conjugated enyne 151 under phase-transfer conditions[120]. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Intramolecular reaction can be used for polycyclization reaction[275]. In the so-called Pd-catalyzed cascade carbopalladation of the polyalkenyne 392, the first step is the oxidative addition to alkenyl iodide. Then the intramolecular alkyne insertion takes place twice, followed by the alkene insertion twice. The last step is the elimination of/3-hydrogen. In this way, the steroid skeleton 393 is constructed from the linear diynetriene 392(276]. 

Interesting formation of the fulvene 422 takes place by the reaction of the alkenyl bromide 421 with a disubstituted alkyne[288]. The indenone 425 is prepared by the reaction of o-iodobenzaldehyde (423) with internal alkyne. The intermediate 424 is formed by oxidative addition of the C—H bond of the aldehyde and its reductive elimination affords the enone 425(289,290]. 

Usually, iodides and bromides are used for the carbonylation, and chlorides are inert. I lowever, oxidative addition of aryl chlorides can be facilitated by use of bidcntatc phosphine, which forms a six-membered chelate structure and increa.scs (he electron density of Pd. For example, benzoate is prepared by the carbonylation of chlorobenzene using bis(diisopropylphosphino)propane (dippp) (456) as a ligand at 150 [308]. The use of tricyclohexylphosphine for the carbonylation of neat aryl chlorides in aqueous KOH under biphasic conditions is also recommended[309,310]. 

The most interesting and difficult cross-coupling is alkyl-alkyl coupling, because oxidative addition of alkyl halides having /i-hydrogen is slow. In addition, easy elimination of /d-hydrogen is expected after the oxidative addition. 

The decarbonylation-dehydration of the fatty acid 887 catalyzed by PdCl2(Ph3P)2 fO.Ol mol%) was carried out by heating its mixture with acetic-anhydride at 250 C to afford the terminal alkene 888 with high selectivity and high catalyst turnover number (12 370). The reaction may proceed by the oxidative addition of Pd to the mixed anhydride[755]. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

The a-bromo-7-lactone 901 undergoes smooth coupling with the acetonyltin reagent 902 to afford the o-acetonyl-7-butyrolactone 903[763j. The o-chloro ether 904, which has no possibility of //-elimination after oxidative addition, reacts with vinylstannane to give the allyl ether 905, The o -bromo ether 906 is also used for the intramolecular alkyne insertion and transmetallation with allylstannane to give 907[764],... 

On the other hand, the halohydrin (chloro and bromo) 908 is converted into a ketone via oxidative addition and //-elimination in boiling benzene with catalysis by Pd(OAc)2 and tri(o-tolyl)phosphine in the presence of K2C03[765,766],... 

The Pd-catalyzed elimination of the mesylate 909 at an anomeric center, although it is a saturated pseudo-halide, under mild conditions is explained by the facile oxidative addition to the mesylate C—O bond, followed by elimination of /3-hydrogen to give the enol ether 910[767],... 

---