Back to Table of Contents

46043-G1
Catalytic Enantio- and Diastereoselective Allylations with Nucleophilic π-Allylpalladium Complexes

Elizabeth R. Jarvo, University of California, Irvine

Efficient catalytic reactions enable the production of bulk and fine chemicals from petroleum-based resources. Despite the advanced state of synthetic chemistry serious challenges remain. As such, the development of new catalytic processes is a critical component of petroleum research. In this project we are developing a new chemical reactions, umpolung allylation reaction of electrophiles by π-allylpalladium intermediates. Current methods for allylation reactions require toxic or expensive allylating agents. The proposed methods are atom-economical, generate non-toxic byproducts, and employ inexpensive starting materials as feedstocks. Therefore, these reactions would be amenable to use on process scale for the preparation of pharmaceutical agents and fine chemicals.

In the first year of funding from the PRF we demonstrated that N-heterocyclic carbene (NHC)-ligated allylpalladium complexes are a new class of nucleophiles and that they react with aldehydes. We also demonstrated that these complexes catalyze allylation reactions of aldehydes. The results of our studies have been reported in a publication: Barczak, N.T.; Grote, R.E.; Jarvo E.R. Organometallics, 2007, 26, 4863-4865.

Stoichiometric Allylation Reactions (Organometallics, 2007, 26, 4863-4865).

We examined a series of π-allylpalladium complexes to evaluate the ability of electron-rich monodentate and bidentate phosphine and NHC ligands to promote nucleophilic attack. Complexes were prepared according to literature procedures. 1H NMR spectroscopic data for all complexes are consistent with cationic η3-allylpalladium complexes. Isomerization of the allyl fragment is observed and occurs by coordination of the counterion or solvent to afford η1-allylpalladium complexes. Our crystal structure of complex confirms that the NHC-pyridine ligand binds to palladium in a bidentate fashion with a bite angle of 87o.

Complexes containing bidentate NHC ligands react with benzaldehyde to afford palladium alkoxides. Complexes prepared from bidentate phosphines such as BINAP did not react with benzaldehyde, nor did a monodentate NHC ligand complex. Although complexes prepared from electron-rich phosphines such as Me-DuPhos react with benzaldehyde, these complexes decompose to afford phosphonium salts, resulting from attack of the phosphine on the allylpalladium.

The nature of the counterion (X-) had a strong impact on the reactivity of the complexes. Coordinating counterions, such as chloride and acetate, afforded more reactive complexes than those containing non-coordinating counterions (tetrafluoroborate or BAr4F ). This effect may be due to the increased ability of the counterion to coordinate to palladium to form the more nucleophilic η1-allylpalladium complex.

A variety of aldehydes react with NHC-ligated allylpalladium complexes. Electron-deficient aldehydes reacted most quickly: p-nitrobenzaldehyde reacted to provide quantitative conversion of palladium complex to product after two hours. Electron-rich aromatic and even aliphatic aldehydes proceed to full conversion within eight hours.

Stoichiometric crotylation of benzaldehyde affords branched alcohol with high regioselectivity as a mixture of diastereomers. These results are similar to observations by Yamamoto and Szabó in related palladium-catalyzed crotylation reactions. Formation of the branched product is consistent with reaction via the more stable γ-substituted η-crotylpalladium complex. Reaction of benzyl benzaldimine with allylpalladium complex 12a also affords homoallylic amine.

Catalytic Allylation Reactions with Allylstannanes and Allylsilanes.

We hypothesized that the nucleophilic allylpalladium complexes that we identified could catalyze umpolung allylation reactions wherein, in analogy to studies by Yamamoto and Szabó, allylstannanes are employed as transmetallating agents. We validated this hypothesis, first by examining reactions of a series of aldehydes with allyltributylstannane, using 10 mol% of allylpalladium complexes. The reactions proceeded smoothly, and as in the stoichiometric allylation reaction, electron-poor aromatic aldehydes reacted most quickly. Of the three bidentate NHC-ligated complexes examined, pyridine-carbene complex containing the NHC-pyridine ligand was the most reactive, in contrast to our observations in the stoichiometric allylation reaction.

Catalytic Redox Allylation Reactions.

We hypothesized that a catalytic allylation reaction of electrophiles using allylic halides could be achieved by a redox mechanism. We have demonstrated the first silver-catalyzed redox allylation reaction of aldehydes and determined that Mn0 is a suitable reducing agent for this reaction. Treatment of benzaldehyde and allylbromide with AgBr (10 mol%) in the presence of stoichiometric quantities of Mn0 affords the desired homoallylic alcohol. This reaction is extremely practical because the catalyst and reagents are very inexpensive and the byproducts, manganese salts, are non-toxic. We are currently developing the scope of this reaction, and are preparing a manuscript for publication.

Back to top