Bis(dibenzylideneacetone)palladium(0)

(PhCH=CHCOCH=CHPh)2Pd

[32005-36-0]  · C34H28O2Pd  · Bis(dibenzylideneacetone)palladium(0)  · (MW 575.01)

(catalyst for allylation of stabilized anions,1 cross coupling of allyl, alkenyl, and aryl halides with organostannanes,2 cross coupling of vinyl halides with alkenyl zinc species,3 cyclization reactions,4 and carbonylation of alkenyl and aryl halides5)

Physical Data: mp 135 °C (dec).

Form Supplied in: solid.

Preparative Method: prepared by adding sodium acetate to a hot methanolic solution of dibenzylideneacetone and Na2[Pd2Cl6], cooling, filtering, washing with MeOH, and air drying.6

Handling, Storage, and Precautions: moderately air stable in the solid state; slowly decomposes in solution to metallic palladium and dibenzylideneacetone.

Allylation of Stabilized Anions.

Pd(dba)2 is an effective catalyst for the coupling of electrophiles and nucleophiles, and has found extensive use in organic synthesis (for a similar complex with distinctive reactivities, see also Tris(dibenzylideneacetone)dipalladium). Addition of a catalytic amount of Pd(dba)2 activates allylic species, such as allylic acetates or carbonate derivatives, toward nucleophilic attack.1 The intermediate organometallic complex, a p-allylpalladium species, is formed by backside displacement of the allylic leaving group, and stereochemical inversion of the original allylic position results. Subsequent nucleophilic attack on the external face of the allyl ligand displaces the palladium in this double inversion process to regenerate the original stereochemical orientation (eq 1).7 The allylpalladium intermediate can also be generated from a variety of other substrates, such as allyl sulfones,8 allenes,9 vinyl epoxides,10 or a-allenic phosphates.11 In general, the efficiency of Pd(dba)2 catalysis is optimized through the addition of either Triphenylphosphine or 1,2-Bis(diphenylphosphino)ethane (dppe).

The anions of malonate esters,12 cyclopentadiene,12 b-keto esters,13 ketones,13,14 aldehydes,14 a-nitroacetate esters,15 Meldrum's acid,15 diethylaminophosphonate Schiff bases,16 b-diketones,17 b-sulfonyl ketones and esters,17 and polyketides18,19 represent the wide variety of carbon nucleophiles effective in this reaction. Generation of the stabilized anions normally is accomplished by addition of Sodium Hydride, Potassium Hydride, or basic Alumina.15 However, when allyl substrates such as allylisoureas,14 allyl oxime carbonates,17 or allyl imidates20 are used, the allylation reaction proceeds without added base. Nitrogen nucleophiles, such as azide10 and nucleotide21 anions, are useful as well.

The coupling reaction generally proceeds regioselectively with attack by the nucleophile at the least hindered terminus of the allyl moiety,22 accompanied by retention of alkene geometry (eq 2). Even electron-rich enol ethers can be used as the allylic moiety when an allylic trifluoroacetyl leaving group is present.23 When steric constraints of substrates are equivalent, attack will occur at the more electron rich site.19 Although this reaction is usually performed in THF, higher yields and greater selectivity are observed for some systems with the use of DME, DMF, or DMSO.14,16,20 Alternatively, Pd(dba)2 can promote efficient substitution of allylic substrates in a two-phase aqueous-organic medium through the use of P(C6H4-m-SO3Na)3 as a phase transfer ligand.24

Intramolecular reaction of a b-dicarbonyl functionality with a p-allyl species can selectively produce three-,25 five-,25 or six-membered26 rings (eq 3).

Asymmetric Allylation Reactions.

Employing chiral bidentate phosphine ligands in conjunction with Pd(dba)2 promotes allylation reactions with moderate to good enantioselectivities, which are dependent upon the solvent,27 counterion,28 and nature of the allylic leaving group.27 Chiral phosphine ligands have been used for the asymmetric allylation of a-hydroxy acids (5-30% ee),29 the preparation of optically active methylenecyclopropane derivatives (52% ee),22 and chiral 3-alkylidenebicyclo[3.3.0]octane and 1-alkylidenecyclohexane systems (49-90% ee).27 Allylation of a glycine derivative provides a route to optically active a-amino acid esters (eq 4).28 The intramolecular reaction can produce up to 69% ee when vicinal stereocenters are generated during bond formation (eq 5).30

Cross-Coupling Reactions.

Allylic halides,5,31 aryl diazonium salts,32 allylic acetates,33 and vinyl epoxides34 are excellent substrates for Pd(dba)2 catalyzed selective cross-coupling reactions with alkenyl-, aryl-, and allylstannanes. The reaction of an allylic halide or acetate proceeds through a p-allyl intermediate with inversion of sp3 stereochemistry, and transmetalation with the organostannane followed by reductive elimination results in coupling from the palladium face of the allyl ligand. Coupling produces overall inversion of allylic stereochemistry, a preference for reaction at the least substituted carbon of the allyl framework, and retention of allylic alkene geometry. In addition, the alkene geometry of alkenylstannane reagents is conserved (eq 6). Functional group compatibility is extensive, and includes the presence of CO2Bn, OH, OR, CHO, OTHP, b-lactams, and CN functionality.

Similar methodology is used for the coupling of alkenyl halides and triflates with 1) alkenyl-, aryl-, or alkynylstannanes,35 2) alkenylzinc species,3,36 or 3) arylboron species.37 This methodology is applied in the synthesis of cephalosporin derivatives (eq 7),35 and can be used for the introduction of acyl3,36 and vinylogous acyl3 equivalents (eq 8).

Intramolecular Reaction with Alkenes.

Palladium p-allyl complexes can undergo intramolecular insertion reactions with alkenes to produce five- and six-membered rings through a metallo-ene-type cyclization.4 This reaction produces good stereoselectivity when resident chirality is vicinal to a newly formed stereogenic center (eq 9), and can be used to form tricyclic and tetracyclic ring systems through tandem insertion reactions.38 In the presence of Pd(dba)2 and triisopropyl phosphate, a,b-alkynic esters and a,b-unsaturated enones undergo intramolecular [3 + 2] cycloaddition reactions when tethered to methylenecyclopropane to give a bicyclo[3.3.0]octane ring system (eq 10).39

Carbonylation Reactions.

In the presence of CO and Pd(dba)2, unsaturated carbonyl derivatives can also be prepared through carbonylative coupling reactions. Variations of this reaction include the initial coupling of allyl halides with carbon monoxide, followed by a second coupling with either alkenyl- or arylstannanes (eq 11).5 This reaction proceeds with overall inversion of allylic sp3 stereochemistry, and retains the alkene geometry of both the allyl species and the stannyl group. Similarly, aryl and alkenyl halides will undergo carbonylative coupling to generate intermediate acylpalladium complexes. Intermolecular reaction of these acyl complexes with HSnBu3 produces aldehydes,35,40 while reaction with MeOH or amines generates the corresponding carboxylic acid methyl ester41 or amides, respectively.42

Palladium acyl species can also undergo intramolecular acylpalladation with alkenes to form five- and six-membered ring g-keto esters through exocyclic alkene insertion (eq 12).43 The carbonylative coupling of o-iodoaryl alkenyl ketones is also promoted by Pd(dba)2 to give bicyclic and polycyclic quinones through endocyclization followed by b-H elimination.44 Sequential carbonylation and intramolecular insertion of propargylic and allylic alcohols provides a route to g-butyrolactones (eq 13).45


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John R. Stille

Michigan State University, East Lansing, MI, USA



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