[74790-18-4]  · C62H54P4Pd  · Bis(triphenylphosphine)[1,2-bis(diphenylphosphino)ethane]palladium(0)  · (MW 1029.42)

(useful for trimethylenemethane cycloadditions;1,2 sulfonylation or amination with epoxy nitro compounds;3 allylic alkylation and amination of nitro compounds;4,5 rearrangement of 2,3-epoxy ketones to b-diketones;6,7 alkylation of enol stannanes;8 opening of vinyloxetanes;9 and macrocyclizations10,11)

Solubility: sol THF, toluene, DMF, and MeCN.

Form Supplied in: generated in situ.

Preparative Method: in situ by the addition of slightly more than 1 equiv of 1,2-Bis(diphenylphosphino)ethane (dppe) to 1 equiv of Tetrakis(triphenylphosphine)palladium(0).

Handling, Storage, and Precautions: as with most palladium(0) catalysts, this reagent should be used under an inert atmosphere and should not be allowed to sit for long periods of time in solution prior to use.

Trimethylenemethane Cycloadditions.

Trimethylenemethane (TMM) cycloaddition is an important tool in the synthesis of five-membered carbocycles.1 The use of bis(triphenylphosphine)[1,2-bis(diphenylphosphino)ethane]palladium(0) (1; 3-9 mol %) with (2-acetoxymethylallyl)trimethylsilane (2) generates the TMM-Pd complex which, in turn, undergoes a [3 + 2] cycloaddition specifically with alkenes bearing an ester, lactone, nitrile, ketone, or sulfone moiety (eq 1). Trans-alkenes provide mainly the trans stereoisomer (95:5, t:c) while cis-alkenes isomerize to give a mixture of cis and trans products. The presence of 0.5-1 equiv of dppe in relation to palladium prolongs the lifetime of the catalyst and prevents the deposition of palladium black. An alternative catalytic system, which employs palladium(II), does not produce a significant difference in yields. However, the use of catalytic palladium(II) has two advantages: (1) the nature of the ligands of palladium(II) can easily be altered and (2) palladium(II) is not air-sensitive.

Trost extends his TMM methodology to include intramolecular [3 + 2] cycloadditions (eq 2).2 With the use of catalyst (1), bicyclic compounds are effectively prepared in one step from acyclic substrates. Concomitant formation of five-membered rings yields only the cis-fused bicyclo[3.3.0]octanes (n = 1). Moderate yields are obtained for the formation of a six-membered ring (n = 2), and the ratio of cis to trans fused ring systems is 2:1. For the intramolecular reaction with TMM, Bis[1,2-bis(diphenylphosphino)ethane]palladium(0) is an efficient catalyst. The use of (dppe)2Pd and added dppe, or the use of Tetrakis(triphenylphosphine)palladium(0) with additional triphenylphosphine, produces the cyclized substrate in significantly lower yields. Catalytic Palladium(II) Acetate (5 mol %) with Triisopropyl Phosphite in the presence of N,O-Bis(trimethylsilyl)acetamide gives superior yields over catalyst (1) for the substrate in which n = 2, R1 = CO2Me and R2 = SO2Ph.

Epoxide Opening with Nucleophilic Substitution.

In the presence of (1), which is generated in situ, b-alkyl-b,g-epoxynitro compounds undergo epoxide opening, and subsequent displacement of the nitro group by various nucleophiles results (eq 3).3 Nucleophiles that efficiently displace the nitro group are Sodium Benzenesulfinate and Piperidine. Nucleophilic attack on the p-allyl intermediate is regiospecific for five-membered ring substrates, but only marginal regioselectivity is observed for the reaction of the six-membered ring substrates (eq 3). The absence of dppe results in a slight decrease in the yield of the desired product by 5-10%.

Allylic Alkylation/Amination and Denitration of Nitro Compounds.

In a closely related study, complex (1) catalyzes substitutions of allylic nitro compounds with secondary amines and stabilized carbanions such as malonic and b-keto esters.4 For cyclic allylic nitro compounds, the use of triphenylphosphine provides higher yields than when dppe is used as the co-ligand. Generally, five-membered ring substrates produce a single regioisomer in moderate yields, while the six-membered substrate gives a mixture of two regioisomers (eq 4). In the palladium-catalyzed allylic alkylation and amination of primary nitro compounds, mixtures of regioisomers and diastereomers are produced unless a sterically hindered alkene is used (eq 5). In this reaction, preferential bond formation occurs at the primary allylic carbon.

Compound (1) is also used for the catalysis of the denitroamination of a-nitroalkenes (eq 6).4,5 Normally, a-nitroalkenes are excellent Michael acceptors. However, in the presence of (1) and a secondary amine, allylic amination occurs accompanied by denitration. In acyclic substrates the regiospecific nucleophilic attack occurs at the less hindered carbon, and b-hydride elimination yields only the (E) isomer. This same type of reaction proceeds with Sodium Benzenesulfinate as the nucleophile and Triethylamine as the base. Again, only the (E) isomer is produced as a result of nucleophilic attack at the least hindered site. The dppe ligand is thought to have two functions in the denitrosulfonylation. Dppe is believed not only to serve as an additional ligand for palladium, but also to function as a base in the isomerization of the a-nitroalkenes to the active allylic species.


The rearrangement of 2,3-epoxy ketones to b-diketones is also facilitated by (1) (eq 7).6 Treatment of 2,3-epoxy ketones with catalytic Tetrakis(triphenylphosphine)palladium(0) and dppe in equimolar amounts produces b-diketones in moderate to excellent yields. This methodology presents a fairly mild procedure for the preparation of b-diketones under neutral and aprotic conditions as opposed to the strongly basic conditions of the Claisen condensation. The addition of dppe significantly improves the yields of b-diketone products, and the use of dppe is necessary to obtain a reasonable reaction rate and to avoid metal precipitation, which deactivates the catalyst. In a similar manner, diethyl (2,3-epoxy-4-oxoalkyl)phosphonates rearrange to give diethyl (2,4-dioxoalkyl)phosphonates promoted by the (dppe)Pd(PPh3)2 catalyst system (eq 8).7


Polyalkylation of enolates presents a problem for synthetic chemists. One procedure that promotes monoalkylation with high regioselectivity uses (1) to catalyze the coupling of enol stannanes with allyl acetates (eq 9).8 Enol stannanes are alkylated with bifunctional silicon conjunctive reagents. Generally, the regioselectivity for alkylation with compound (3) favors alkylation a to the silicon. 3-Acetoxy-1-(trimethylsilyl)-1-propene can be used as an alternative to compound (3).

Oxetane Opening with Allylic Alkylation.

Vinyloxetanes are alkylated through nucleophilic opening of the oxetane to yield homoallylic alcohols (eq 10).9 Although the formation of disubstituted alkenes can be accomplished simply with Pd(PPh3)4, synthesis of trisubstituted alkenes requires the use of compound (1). Various nucleophiles can take part in this general reaction, yet only stabilized enolates (b-diketones, malonates, and b-cyano esters) produce successful formation of trisubstituted alkenes.


Macrocyclization is accomplished by generating the p-allylpalladium species from the allylic pivalate with compound (1) (eq 11).10 Intramolecular phenylsulfonylacetate attack of the p-allylpalladium species at the least hindered carbon generates the macrocyclic product used as an intermediate in the synthesis of isolobophytolide. A key step in the synthesis of antibiotic A26771B also employs this macrocyclization methodology (eq 12).11 In this cyclization the intermediate p-allyl palladium species is generated from an acetate which is allylic to an enol ether. This methodology offers an alternative route to macrolactone formation. The conditions of this cyclization are tolerated by enol ethers, sulfones, esters, alkenes and hydroxy groups.

1. (a) Trost, B. M.; Chan, D. M. T. JACS 1979, 101, 6429. (b) Trost, B. M.; Chan, D. M. T. JACS 1983, 105, 2315.
2. Trost, B. M.; Grese, T. A.; Chan, D. M. T. JACS 1991, 113, 7350.
3. Tamura, R.; Kato, M.; Saegusa, K.; Oda, D.; Egawa, T.; Yamamoto, T. JOC 1987, 52, 1642.
4. Tamura, R.; Kai, Y.; Kakihana, M.; Hayashi, K.; Tsuji, M.; Nakamura, T.; Oda, D. JOC 1986, 51, 4375.
5. Tamura, R.; Hayashi, K.; Kai, Y.; Oda, D. TL 1984, 25, 4437.
6. Suzuki, M.; Watanabe, A.; Noyori, R. JACS 1980, 102, 2095.
7. Ohler, E.; Kang, H.-S.; Zbiral, E. S 1988, 623.
8. Trost, B. M.; Self, C. R. JOC 1984, 49, 468.
9. Larock, R. C.; Stolz-Dunn, S. K. TL 1989, 30, 3487.
10. (a) Marshall, J. A.; Andrews, R. C.; Lebioda, L. JOC 1987, 52, 2378. (b) Trost, B. M.; Vos, B. A.; Brzezowski, C. M.; Martina, D. P. TL 1992, 33, 717.
11. Trost, B. M.; Brickner, S. J. JACS 1983, 105, 568.

Arthur E. Harms & John R. Stille

Michigan State University, East Lansing, MI, USA

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