Oxidative addition allylation

In combination with the inversion step in the oxidative addition, allyl—X ir-allyl precursors show overall retention of configuration relative to the C—X bond via a double inversion process (equation 152). 

The most widely used preparative method of allylindium(m) or propargylindium(lll) compounds is the oxidative addition of metallic indium or indium(l) halides to allylic or propargyl substrates.4 26 27 Allylic bromides and iodides serve as good allylic sources without any other activation. In the case of allylic chlorides, a proper additive such as lithium iodide is required to promote the oxidative addition. Allylic indium compounds prepared by oxidative addition of metallic indium are considered to exist as the sesquihalide structure (allyl jImXj), which has been... 

Allyl carbonates are particularly useful allylic substrates. Thus, in addition to their high reactivity in oxidative addition, allyl carbonates have the advantage that the ally-lation reaction can be conducted under neutral conditions without an added base. The (7t-allyl)palladium intermediate (17) derived from an allylic carbonate has a carbonate anion that serves as a masked base to generate carbon nucleophiles (eq (112)) [143]. 

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. 

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. 

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],... 

In addition, a catalytic version of Tt-allylpalladium chemistry has been devel-oped[6,7]. Formation of the Tr-allylpalladium complexes by the oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of the complex with soft carbon nucleophiles are the basis of catalytic allylation. After the reaction, Pd(0) is reformed, and undergoes oxidative addition to the allylic compounds again, making the reaction catalytic.-In addition to the soft carbon nucleophiles, hard carbon nucleophiles of organometallic compounds of main group metals are allylated with 7r-allylpalladium complexes. The reaction proceeds via transmetallation. These catalytic reactions are treated in this chapter. 

Allylic acetates are widely used. The oxidative addition of allylic acetates to Pd(0) is reversible, and their reaction must be carried out in the presence of bases. An important improvement in 7r-allylpalladium chemistry has been achieved by the introduction of allylic carbonates. Carbonates are highly reactive. More importantly, their reactions can be carried out under neutral con-ditions[13,14]. Also reactions of allylic carbamates[14], allyl aryl ethers[6,15], and vinyl epoxides[16,17] proceed under neutral conditions without addition of bases. 

Furthermore, the catalytic allylation of malonate with optically active (S)-( )-3-acetoxy-l-phenyl-1-butene (4) yields the (S)-( )-malonates 7 and 8 in a ratio of 92 8. Thus overall retention is observed in the catalytic reaction[23]. The intermediate complex 6 is formed by inversion. Then in the catalytic reaction of (5 )-(Z)-3-acetoxy-l-phenyl-l-butene (9) with malonate, the oxidative addition generates the complex 10, which has the sterically disfavored anti form. Then the n-a ir rearrangement (rotation) of the complex 10 moves the Pd from front to the rear side to give the favored syn complex 6, which has the same configuration as that from the (5 )-( )-acetate 4. Finally the (S)-( )-mal-onates 7 and 8 are obtained in a ratio of 90 10. Thus the reaction of (Z)-acetate 9 proceeds by inversion, n-a-ir rearrangement and inversion of configuration accompanied by Z to isomerization[24]. 

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

C-Allyl Complex Formation. AHyl hahde, aHyl ester, and other aHyl compounds undergo oxidative addition reactions with low atomic valent metal complexes to form TT-aHyl complexes. This is a specific reaction of aHyl compounds. 

The 3,5-bis(trifluoromethyl)pyrazolate analog [Ir(cod)(/x-3,5-(CF3)2pz)]2 does not enter into oxidative addition with iodine, methyl iodide, or acetylenes. The mixture of pyrazolate and 3,5-bis(trifluoromethyl)pyrazolate gives [(rj -codllrf/x-pz)(/L-3,5-(CF3)2pz)Ir(rj -cod)], which reacts with bis(trifluoromethyl)acetylene in a peculiar manner [83JCS(CC)580], producing 145, where 3,5-bis(trifluoromethyl) pyrazolate is replaced by the ethylene bridge and the rj -coordination mode of one of the cod ligands is converted into the rj -allylic mode. 

For trisubstituted olefins, the nucleophile attacks predominantly at the less substituted end of the allyl moiety, e.g. to afford a 78 22 mixture of 13 and 14 (equation 7). Both the oxidative addition of palladium(O) and the subsequent nucleophilic attack occur with inversion of configuration to give the product of net retention7. The synthesis of the sex pheromone 15 of the Monarch butterfly has been accomplished by using bis[bis(l,2-diphenylphosphinoethane)]palladium as a catalyst as outlined in equation 87. A substitution of an allyl sulfone 16 by a stabilized carbon nucleophile, such as an alkynyl or vinyl system, proceeds regioselectively in the presence of a Lewis acid (equation 9)8. The... 

Chlorination of the Cp Ru(amidinate) complexes is readily achieved by treatment with CHCI3, while oxidative addition of allylic halides results in formation of cationic Ti-allyl ruthenium(IV) species (Scheme 243). °... 

As far as the reactions with benzyl chlorides are concerned (74), the oxidative addition of benzyl chloride and substituted benzyl chlorides to palladium atoms yields rj -benzylpalladium chloride dimers. The parent compound, bis(l,2,3-7 -benzyl)di-/i,-chloro-palladium(II), quantitatively adds four molecules of PEts by first forcing the rj -benzyl-iy -benzyl transformation, with subsequent breakage of the Pd-Cl bridges to form trans-bistPEtsKbenzyDchloroPddI). The spectral characteristics of the parent molecule are indicative of the allylic type of bonding. Similar i7 -benzyl compounds were formed from 4-methylbenzyl chloride, 2-chloro-l,l,l-trifluoro-2-phenylethane, and 3,4-dimethylbenzyl chloride. 

The proposed mechanism for Fe-catalyzed 1,4-hydroboration is shown in Scheme 28. The FeCl2 is initially reduced by magnesium and then the 1,3-diene coordinates to the iron center (I II). The oxidative addition of the B-D bond of pinacolborane-tfi to II yields the iron hydride complex III. This species III undergoes a migratory insertion of the coordinated 1,3-diene into either the Fe-B bond to produce 7i-allyl hydride complex IV or the Fe-D bond to produce 7i-allyl boryl complex V. The ti-c rearrangement takes place (IV VI, V VII). Subsequently, reductive elimination to give the C-D bond from VI or to give the C-B bond from VII yields the deuterated hydroboration product and reinstalls an intermediate II to complete the catalytic cycle. However, up to date it has not been possible to confirm which pathway is correct. 

A possible reaction mechanism shown in Scheme 7-10 includes (a) oxidative addition of the S-H bond to Pd(0), (b) insertion of the allene into the Pd-H bond to form the tt-allyl palladium 38, (c) reductive elimination of allyl sulfide, (d) oxidative addition of the I-aryl bond into the Pd(0), (e) insertion of CO into the Pd-C bond, (f) insertion of the tethered C=C into the Pd-C(O) bond, and (g) P-elimination to form 37 followed by the formation of [baseHjI and Pd(0). 

Kurosawa et al. have reported that the relative stability of the ti-allyl palladium thi-olate 39 and the allyl sulfide/Pd(0) was highly ligand dependent. In the presence of PPhs or P(OMe)3 the stability was in favor of reductive elimination (Eq. 7.28), while in the presence of olefin or in the absence of any additional ligand the stability was in favor of oxidative addition (Eq. 7.29) [38]. This can explain the reactivity of the n-allyl palladium thiolate 33 and 38 proposed in Eq. (7.24) and path (c) of Scheme 7-10. The complex 33 should react with PhSH, but C-S bond-forming reductive elimination has to be suppressed in order to obtain the desired product 32. On the other hand, the complex 38 requires the phosphine ligand to promote the C-S bond-forming reductive elimination. 

Fukuzawa et al. reported that Pd-catalyzes the reaction of allylacetate, (PhSe)2 and Smfi to form allylselenide 71 (Eq. 7.52) [57]. The complex 72, which can be generated by the contact of (PhSe)2 with Pd(0) in the actual reaction mixture, was hardly active as a catalyst, indicating that the reaction proceeded via oxidative addition of allyl acetate to Pd(0) rather than oxidative addition of (PhSe)2 to Pd(0). 

Allyl carbonate esters are also useful hydroxy-protecting groups and are introduced using allyl chloroformate. A number of Pd-based catalysts for allylic deprotection have been developed.209 They are based on a catalytic cycle in which Pd° reacts by oxidative addition and activates the allylic bond to nucleophilic substitution. Various nucleophiles are effective, including dimedone,210 pentane-2,4-dione,211 and amines.212... 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

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