Alkylpalladium complexes

Migration of a hydride ligand from Pd to a coordinated alkene (insertion of alkene) to form an alkyl ligand (alkylpalladium complex) (12) is a typical example of the a, /(-insertion of alkenes. In addition, many other un.saturated bonds such as in conjugated dienes, alkynes, CO2, and carbonyl groups, undergo the q, /(-insertion to Pd-X cr-bonds. The insertion of an internal alkyne to the Pd—C bond to form 13 can be understood as the c -carbopa-lladation of the alkyne. The insertion of butadiene into a Ph—Pd bond leads to the rr-allylpalladium complex 14. The insertion is usually highly stereospecific. 

Furthermore, treatment of the aminopalladation product with bromine affords aziridines[176]. The aziridine 160 was obtained stereoselectively from methylamine and 1-decene in 43% yield. The aminopalladation of PdCl2 complexes of ethylene, propylene, and 1-butene with diethylamine affords the unstable ir-alkylpalladium complex 161, which is converted into the stable chelated acylpalladium complex 162 by treatment with CO[177],... 

Another approach is based on the palladium-catalyzed intramolecular carbocyclization of the allylic acetate moiety with the alkene moiety (Scheme 96). After the formation of a 7t-allylpalladium complex, with the first double bond the intramolecular carbometallation of the second double bond occurs to form a new C-C bond. The fate of the resulting alkylpalladium complex 393 depends on the possiblity of /3-elimination. If /3-elimination is possible, it generates a metallated hydride and furnishes the cycloadduct 394. This cyclization could be viewed as a pallada-ene reaction, in which palladium replaces the hydrogen atom of the allylic moiety.231... 

The reaction was further applied to the synthesis of spiro heterocycles (Scheme 16.4) [8], The oxidative addition of an iodide to a Pd(0) species generates an ArPdl species, into which an internal olefin inserts to form an alkylpalladium complex otherwise difficult to access. Allene participates in the reaction at this stage to provide a jt-allylpalladium complex, which is attacked by the amine intramolecularly to afford the procuct. 

A one-pot synthesis of 3,3-disubstituted indolines was achieved by taking advantage of a sequential carbopalladation of allene, nucleophile attack, intramolecular insertion of an olefm and termination with NaBPh4 (Scheme 16.6) [10]. First, a Pd(0) species reacts with iodothiophene selectively to afford ArPdl, probably because the oxidative addition step is facilitated by coordination with the adjacent sulfur atom. Second, the ArPdl adds to allene, giving a Jt-allylpalladium complex, which is captured by a 2-iodoaniline derivative to afford an isolable allylic compound. Under more severe conditions, the oxidative addition of iodide to Pd(0) followed by the insertion of an internal olefm takes place to give an alkylpalladium complex, which is transmetallated with NaBPh4 to release the product. 

In spite of the difficulties mentioned above, Brookhart and co-workers succeeded in measuring the barrier for ethene insertion into (dppp)PdC(0)CH3+ at 160 K, starting from the ethene adduct, generated at still lower temperatures, in the absence of CO. The barrier measured (AG ) amounted to only 51.4 kJ/mol, i.e. the reaction is faster than the insertion of CO in an ionic alkylpalladium complex. The barrier of insertion of ethene into a palladium methyl species or palladium ethyl species was higher, at 67 kJ/mol at 233 K. As for the CO insertion described above, these values concern the barriers in preformed ethene adducts at higher temperatures the overall barrier will be higher, because alkene coordination will be disfavoured by entropy and competition with CO and solvent. Formation of CO adducts will also be less favourable at higher temperatures. 

Chelating alkenes such as allylic10 and homoallylic11 amines and sulfides underwent alkylation by a range of stabilized carbanions to produce stable cr-alkylpalladium(II) complexes. In these cases the regioselectivity was strictly governed by the inherent stability of a five (versus four or six) membered chelate cr-alkylpalladium complex, with allylic systems (Scheme 5) being alkylated at the more sub-... 

Alkylpalladium complexes generated by oxidative addition of Pd(0) to alkyl halides with a /3 hydrogen can undergo /3-elimination to yield an alkene and a Pd-hydrido complex (as in the Heck reaction Scheme8.7). Nevertheless, this process is relatively slow compared with transmetalations and reductive eliminations, and simple alkyl halides or tosylates with /3 hydrogen can be cross-coupled with carbon nucleophiles under optimized conditions if the nucleophile is sufficiently reactive [9, 73-75] (Scheme8.6). 

In the hydrocarbonation of methylenecyclopropanes 8 with nitriles, the hydro-palladation of 8 with 16 gives the alkylpalladium complexes 23 and/or 24 (Scheme 5). The complex 23 would undergo rearrangement by distal bond cleavage to give the Jt-allylpalladium 25 (route A). The reductive elimination of Pd(0) from 25 produces 9. The palladium complex 24 would isomerize to the Jt-allylpalladium complex 27 via proximal bond cleaved ring-opened intermediate 26 (route B). The reductive elimination of Pd(0) from 27 gives 10. 

The proposed mechanism for a standard Heck reaction is depicted in Scheme 6.5. Generally, a haloalkene or haloarene undergoes oxidative addition to an in situ generated, coordinatively unsaturated 14-electron palladium(O) complex, but other substrates such as tosylates, triflates or diazonium salts can also be applied. Subsequent, sy -insertion into the C=C double bond of a complexed olefin yields a t7-(j -alkenyl) or (j- aryl)alkylpalladium complex. If no hydrogen atom in a pseudo cis-position relative to the palladium is present, an internal rotation step is required prior to syw-elimination of the olefin to afford the traws-olefin product and a palladium(II) hydride complex. The latter is restored to the initial Pd(0) species by base-induced reductive elimination.137"401... 

Palladium salts also promote the addition of nucleophiles to alkenes and alkynes. The Pd-catalyzed additions of nucleophiles to alkynes, which is useful for intramolecular cyclizations such as the isomerization of 2-alkynylphenols to benzofurans, proceeds by exactly the same mechanism as does the Hg-catalyzed reaction. However, the Pd-catalyzed additions of nucleophiles to alkenes takes the course of substitution rather than addition because alkylpalladium complexes are unstable toward /3-hydride elimination. The Pd-catalyzed nucleophilic substitutions of alkenes are discussed later in this chapter (Section 6.3.6). 

Since palladium(II) is electrophilic, olefins are activated toward nucleophiles by coordination to palladium(II) species. The attack of nucleophiles occurs at the more substituted vinylic carbon from the anti side of palladium to give alkylpalladium complexes (eq (92)) [123]. 

The Wacker-type addition is the anti-addition of (most commonly) a heteroatom and a Pd(II) species across a C-C double bond. The Wacker-type oxidations are Pd(II)-catalyzed transformations involving heteroatom nucleophiles and alkenes or alkynes as electrophiles.27 In most of these reactions, the Pd(II) catalyst is converted to an inactive Pd(0) species in the final step of the process, and use of stoichiometric oxidants is required to effect catalytic turnover. For example, the synthesis of furan 33 from a-allyl-p-diketone 32 is achieved via treatment of the substrates with a catalytic amount of Pd(OAc)2 in the presence of a stoichiometric amount of CuCh-28 This transformation proceeds via Pd(II) activation of the alkene to afford 34, which undergoes nucleophilic attack of the enol oxygen onto the alkene double bond to provide alkylpalladium complex 35. p-Hydride elimination of 35 gives 36, which undergoes... 

The first alkylpalladium complex in oxidation state (IV) was isolated by Canty [27]. We obtained the first palladium(IV) metaiiacycies from the reaction... 

Upon warming, alkylpalladium complex 4 underwent P-hydride elimination to generate allylbenzene and Pd(P(t-Bu)2Me)2HBr. This process was inhibited by the presence of excess P(t-Bu)2Me, consistent with a pathway that involves initial dissociation of a phosphine [45]. Oxidative-addition adduct 4 reacted with one equivalent of o-tolylboronic acid to generate the coupling product in 94% yield in addition, it served as a competent catalyst for cross-couplings of alkyl bromides and arylboronic acids. 

The insertion of alkene to Pd-H, which is called hydropalladation of an alkene, affords the alkylpalladium complex 18, and insertion of alkyne to Pd-R bonds... 

Another termination step in a catalytic cycle is syn elimination of hydrogen from carbon at jS-position to Pd in alkylpalladium complexes to give rise to Pd hydride (H-Pd-X) and an alkene. This process is called either jS-hydride elimination or y3-hydrogen elimination . Most frequently used is -hydride elimination , because the y3-H is eliminated as the Pd-hydride (H-Pd-X). The proper and unambiguous term of this process is dehydropalladation in a cis maimer. This is somewhat similar to a El or E2 reaction in organic chemistry, althought it is anti elimination. 

Several Pd(0)-catalyzed reactions which are not covered in Ch ters 2-8 are treated in this chapter. A useful preparative method of A-acylamino acids by the reaction of amides, aldehydes, and CO is known as amidocarbonylation, and cobalt carbonyl is an active catalyst [1], Beller et al. fovmd that the reaction can be also catalyzed by Pd complexes. Reaction of acetamide, cyclohexanecarboxalde-hyde, and CO (60 atm) at 120 °C using ligandless Pd/C as a catalyst in NMP in the presence of LiBr and H2SO4 afforded the acylamino acid 1 in 98 % yield [2]. In this reaction, A-a-hydroxyalkylamide 2 is formed from amide and aldehyde, and converted to the alkylpalladium complex 3. Acylamino acid 1 is formed by CO insertion. 

While neopentyl-type and related cr-alkylpalladium complexes are stable toward dehy-dropalladation, all ordinary alkylpalladium complexes formed by carbopalladation of alkenes do undergo /S-hydride eUminalion more or less rapidly. However, under certain structural precondilions and also, to a certain extent, controlled by the external conditions, rearranganents, further carbopalladations (Sect. IV.3), transmetallations, car-bonylations, or nucleophilic substitutions (e.g., by hydride) can occur prior to /3-dehy-dropalladation. 

The product in Scheme 8, reminiscent of a prostaglandin, is the result of an intramolecular carbopalladation followed by an intermolecular Heck reaction, which becomes possible because the decisive intermediary alkylpalladium complex is lacking an appropriate hydrogen in synperiplanar position for the /3-H-elimination.f ... 

Similarly, the intermediary alkylpalladium complexes, which have to be assumed for the reactions in Scheme 9, have a sufficient lifetime to interact with an additional reagent in these cases reduction by sodium formate takes place. The resulting furobenzofurans are model compounds for the synthesis of aflatoxines. ... 

A number of intramolecular Mizoroki-Heck reactions yield the product consistent with a formal a r/-elimination of the HPdX [11], These experimental findings are in opposition to the generally accepted mechanism of a 5y -elimination however, a reasonable explanation is at hand in most cases. There are two main types of alkenyl derivatives which, if added to an CT-aryl- or cr-alkenylpalladium(II) complex, deliver the formal a ft-elimination product. The first case is intramolecular Mizoroki-Heck reactions with o ,jS-unsaturated carbonyl systems which result in the product of a formal 1,4-addition. The initially formed <7-(y3-aryl)- or <7-(/3-alkenyl)alkylpalladium complex should be long-lived enough to epimerize through a palladium(II) enolate intermediate and, thus, deliver the formal anr/-elimination product through conventional 5yn-elimination (Scheme 6.2). 

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