JT-allyl palladium intermediate

A single reaction has been described in which a palladium-catalyzed reaction was employed to form an alkyne [45], Thus, attempted alkylation of carbonate 145 with dimethyl malonate in the presence of Pd(PPh3)4 gave a mixture of enyne 87 and the alkylation product 86 in a 15 1 ratio (Scheme 14.37). Methoxide caused an elimination in (jT-allyl)palladium intermediate 146, which is apparently faster under these conditions than a reaction with the nucleophile (cf. Eq. 14.9). The synthetic importance of this process seems to be limited. 

Palladium(II) is one of the most important transition metals in catalytic oxidations of allenes [1], Scheme 17.1 shows the most common reactions. Transformations involving oxidative addition of palladium(O) to aryl and vinyl halides do not afford an oxidized product and are discussed in previous chapters. The mechanistically very similar reactions, initiated by nucleophilic attack by bromide ion on a (jt-allene)pal-ladium(II) complex, do afford products with higher oxidation state and are discussed below. These reactions proceed via a fairly stable (jt-allyl)palladium intermediate. Mechanistically, the reaction involves three discrete steps (1) generation of the jt-allyl complex from allene, halide ion and palladium(II) [2] (2) occasional isomeriza-... 

A likely mechanism of these reactions is that they proceed via a (jt-allyl)palladium intermediate 29 or 31 as shown in Scheme 17.12. Intramolecular attack by either... 

Vinyl epoxides and allyHc carbonates are especially useful electrophiles because under the influence of palladium(O) they produce a catalytic amount of base since is an alkoxide anion. This is sufficiently basic to deprotonate most nucleophiles that participate in aUylic alkylations and thus no added base is required with these substrates. The overaU reaction proceeds under almost neutral conditions, which is ideal for complex substrates. The rehef of strain in the three-membered ring is responsible for the epoxide reacting with the paUadium(O) to produce the zwitterionic intermediate. Attack of the negatively charged nucleophile at the less hindered end of the Jt-allyl palladium intermediate preferentially leads to overall 1,4-addition of the neutral nucleophile to vinyl epoxides. 

Pd(0) generated by the action of TPPTS may react in oxidative addition across the C-H bond of CH-acids, and the resulting hydridopalladium intermediate reacts with allylating agent with the formation of either a- or Jt-allyl-palladium intermediate. It is quite noteworthy that the use of aqueous solvent may help the formation of allylpalladium intermediate in an Snl-like process. 

Fttrstner has employed the Trost pyrrole synthesis in the first total synthesis of roseophilin, wherein this A-benzylpyrrole-ring forming step occurred in 70% yield [23]. Backvall has found that primary amines react with dienes under the guidance of Pd(II) to form pyrroles 170 in variable yields [121]. The intermediate Jt-allyl-palladium complexes are quite stable. 

The palladium(II)-catalyzed oxidation of allenes with chloride was studied by Hege-dus et al. [3], In this reaction the dimeric products 4 and 6 as shown in Scheme 17.4 were obtained. The (allene)palladium(II) complex formed can react with chloride ions in two different ways (Scheme 17.4) [4]. Attack at the terminal carbon gives a vinylpalladium intermediate 2 whereas attack at the middle carbon produces a 2-chloro(jt-allyl)palladium complex 3. The former complex is the kinetic intermediate (k2 > kj) and is in equilibrium with the (allene)palladium complex. The 2-chloro(jt-allyl)palladium complex is formed more slowly but is more stable and has been isolated [2]. The vinyl complex can undergo further reaction with excess allene to give a new (jt-allyl)palladium complex, which undergoes attack with chloride to give the observed dimer 6 [3]. The dichloride from attack on the 2-chloro-(jT-allyl)palladium complex 3 was not observed. 

Several catalytic systems have been investigated for hydroamination of unsaturated bonds [16]. Takahashi et al. reported the telomerization of 1,3-dienes in the presence of an amine leading to octadienylamine or allylic amines when palladium catalysts are used in association with monodentate or bidentate phosphine ligands, respectively [17]. Dieck et al. demonstrated the beneficial effect of addition of an amine hydroiodic salt in the hydroamination reaction of 1,3-dienes in which the allylic amines are produced via an intermediate Jt-allyl palladium complex [18]. Coulson reported the Pd-catalyzed addition of amines to allenes where dimerization is incorporated [4]. This reaction presumably proceeds via a cyclic palladium intermediate in which the Pd activates the olefinic bond for nucleophilic attack the reactions are therefore different from pronucleophilic additions. 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

The pioneer work of a catalytic, intramolecular allylic C-H activation was reported by Larock and coworkers in 1996 [7] the reaction underwent the cychzation of tosylamides 1 bearing alkene substituents to afford indoline products. It was suggested that Jt-allyhc palladium intermediates were likely formed during the cychzation (Scheme 2.2). 

Metal-activated alkene additions can be classified as stoichiometric or catalytic processes. Stoichiometric processes for THP synthesis typically involve the use of mercury(II) salts and to a lesser extent iodo and seleno reagents. The progress of intramolecular oxymercuration is determined by the stabiUty of the cationic intermediates. Product stereochemistry is under substrate control and usually leads to the thermodynamically more stable THP product. Catalytic variations generally involve palladium complexes [44], but other transition metals are becoming more common (e.g., Pt [45], Ag [46], Sn [47], Ce [48]). The oxidation state of Pd determines the catalyst reactivity. Palladium(O) complexes are nucleophilic and participate in tetrahydropyran synthesis through jt-allyl cation intermediates, whereas Pd(II) complexes possess electrophilic character and progress through a reversible t-complex. 

The intermediate Jt-allyl complex is formally the palladium(II) complex of an allylic anion that can be represented by the two mesomeric forms shown in Scheme 17.2. It is important to note that this is not a fast equilibrium between two cr-allyl complexes but a stable species where palladium is simultaneously bound to both carbon-1 and carbon-3. All eight atoms of the Jt-allyl moiety are almost in the same plane. All three carbon atoms have sp2 character and the rotation between the Cl-C2 and C2-C3 bonds is blocked. As a consequence of the hindered rotation, four dia-stereomeric Jt-allyl complexes are possible. For example, in Scheme 17.2 both R and R are syn to the hydrogen on carbon-2, therefore this complex is called the syn,syn diastereomer. 

In 1997, Backvall and Jonasson published a procedure for the 1,2-oxidation of terminal allenes 7 [5]. In this case the reaction conditions were chosen so that the (vinyl)palladium complex equilibrates back to the allene complex. Using bromide instead of chloride as a nucleophile, the 2-bromo-jt-allyl complex 9 is the major intermediate present in the reaction mixture. A catalytic reaction was developed with the use of 5 mol% palladium acetate and p-benzoquinone (BQ) as terminal oxidant (Scheme 17.5). 

Good diastereoselectivity was obtained with BQ as the oxidant in acidic media but the reaction times were relatively long (1-2 days at 40 °C). Using the copper(II)-oxy-gen system in slightly basic media permits a much faster reaction (0.5-1 h at 20 °C) with better isolated yields but with poor or even reversed diastereoselectivity. The slower reaction with BQ as oxidant is due to the fact that this oxidant requires an acidic medium, which lowers the nucleophilicity of the acid moiety. It is also likely that BQ or copper(II) has to coordinate to palladium(II) before the second nucleophile can attack to make the Jt-allyl complex more electrophilic. Coordination of cop-per(II) would make a more electrophilic intermediate than coordination of BQ. The relation between reaction time and diastereoselectivity supports a mechanism analogous to that in Scheme 17.7. 

The reaction of an allene with an aryl- or vinylpalladium(II) species is a widely used way of forming a Jt-allyl complex. Subsequent nucleophilic attack on this intermediate gives the product and palladium(O) (Scheme 17.1). Oxidative addition of palladium ) to an aryl or vinyl halide closes the catalytic cycle that does not involve an overall oxidation. a-Allenyl acids 27, however, react with palladium(II) instead of with palladium(O) to afford cr-vinylpalladium(II) intermediates 28 (Scheme 17.12). These cr-complexes than react with either an allenyl ketone [11] or with another alle-nyl acid [12] to form 4-(3 -furanyl)butenolides 30 or -dibutenolides 32, respectively. 

Nonconjugated dienes, namely, allenes and isolated dienes, react preferentially on the terminal double bond.10 Hydrogenation of 1,2-butadiene over palladium yields 1-butene and d.s-2-butene as the main products with moderate discrimination of the two double bonds.68 Deuteration experiments indicated that the dominant syn addition to either the 1,2- or the 2,3-olefinic bond occurs. Different vinyl and Jt-allyl intermediates were invoked to interpret the results.69 70... 

Distinction between enantiodiscrimination by complexation and by alkylation of equilibrating intermediates is less clear in a number of related cases. It is likely that more than one type of chiral discrimination may be involved. For example, when a conformational ly flexible four-membered ring substrate is used for the same reaction, the enantioselectivity was only 56% ee (Eq. 8E.15) [175]. In this case, it has been proposed that equilibration via a tertiary e-palladium species may be possible, switching the origin of enantio-discrimination to the alkylation step. A more contrasting example involves the formation of an asymmetric diene via selective P-elimination of similar diastereomeric Jt-allyl intermediates (Eq. 8E.16). Evidence suggests that the enantio-determining elimination process occurs after the equilibration of the 7t-allyl intermediates [176]. 

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

In the allylic substitution of racemic 2-propenyl acetates or related substrates with the same substituents at 1 and 3 positions, the jt-allylpalladium intermediate containing a meso type 7r-allyl group is formed from both enantiomers of the allylic substrate. Two jt-allyl carbons at the 1- and 3-positions are diastereotopic on coordination of a chiral phosphine ligand to palladium. The asymmetric induction arises from preferential attack by the nucleophile on either of the two diastereotopic TT-allyl carbon atoms (Scheme 2-28). 

The reaction of this allyHc acetate with the sodium salt of Meldrum s acid (structure in margin) demonstrates the retention of configuration in the palladium(0)-catalysed process. The tetraacetate and the intermediate Jt-allyl complex are symmetrical, thus removing any ambiguity in the formation or reaction of the Jt-allyl complex and hence in the regiochemistry of the overall reaction. 

Only the geometry of the rt-allyl ligand in the intermediate metal complex determines the enantioselectivity. Racemization cannot occur via anti attack of a free palladium(O) species onto the xc-allyl complex. A stereoscrambling T-a-n rearrangement is rather unlikely, since it would involve the unfavorable formation of a cr-bond from palladium to a tertiary carbon atom. Ionization of the allylic ester is under stereoelectronic control. In particular, the C —X bond has to be orientated orthogonal to the plane of the double bond. Two enantiomeric conformers of the allylic substrate which are in rapid equilibrium meet this requirement. The chiral palladiuni(O) complex discriminates between these enantiomeric conformers, whose conversion to the corresponding jt-allyl complexes occurs at markedly different rates. 

In 1986 Inanaga et al. found that allylic or propargylic acetates could be reduced in THF by diiodosamarium in the presence of a catalytic amount of a Pd(0) complex and 1 equiv of 2-propanol [160,161]. Some examples are indicated in Scheme 60. The mechanism of the reaction likely involves jt-allyl (or a-allenyl) palladium intermediates which are reduced first to radicals and then to carban-ions (see Scheme 60). A final protonation by the alcohol generates the products. 

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