Palladium-catalyzed selective activation of allyl alcohols as allyl cations, allyl anions, and zwitterionic trimethylenemethanes

Pure and Applied Chemistry, May, 2008 by Yoshinao Tamaru, Masanari Kimura

Abstract: Pd-[Et.sub.3]B catalytic system promotes the generation of allyl cations, allyl anions, and zwitterionic trimethylenemethane species from the corresponding allylic alcohols. Allyl cations react with a wide variety of nucleophiles, e.g., amines, active methylene compounds, 1,3,5-trihydroxybenzene, indoles, aldehydes (at the [alpha]-position). The reaction is extended to dehydrative Grob fragmentation of 1,3-diols. Allyl anions react with aldimines to give homoallyl amines. Zwitterionic trimethylenemethane, generated from 2-methylene-1,3-propanediol, reacts with aldehydes and aldimines to provide 3-methylenecyclopentanols and 3-methylenepyrrolidines, respectively. Vinyl epoxide can be utilized as a synthetic equivalent of 3-butenyl 2-anion-1-cation.

Keywords: allyl alcohols; allyl anions; allyl cations; catalysis; palladium; triethylborane; trimethylenemethane; umpolung.

INTRODUCTION

Allylation reactions, both electrophilic (allylation at the [alpha]-carbons of carbonyls and heteroatoms) and nucleophilic (allylation at the carbonyl carbons) are among the most reliable and useful processes to elaborate molecules into the desired compounds. The ability of hydroxy group as a leaving group is such that electrophilic allylation has been generally performed by converting allyl alcohols into allyl halides (step 1, Scheme 1). In order to perform nucleophilic allylation, a further transformation of allyl halides into allylmetals or allylmetalloids is necessary (step 2, Scheme 1).

This paper describes that both electrophilic and nucleophilic allylations can be performed directly by using allyl alcohols under the catalysis of palladium in the presence of triethylborane ([Et.sub.3]B). This catalytic process is advantageous over the existing methods in many respects (Scheme 1). For example, we can save one step (e.g., halogenation) for the generation of allyl cations and also we can save two steps for the generation of allyl anions. We can avoid the use of acids, bases, metals, and metalloid species. No strictly dry conditions are necessary; in fact, one molecule of water is produced in every one catalytic cycle for the generation of allyl cations and anions. Furthermore, by the combination of these two methods, zwitterionic trimethylenemethane species I can be generated from 2-methylene-1,3-propanediol (Scheme 1) [1].

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Scheme 2 outlines the basic strategy for the direct activation of allyl alcohols catalyzed by Pd and [Et.sub.3]B. Here, [Et.sub.3]B works in two ways. First, by coordination to the hydroxy group, [Et.sub.3]B activates an allyl alcohol toward oxidative addition of Pd(0) upon the allylic C-O bond. [pi]-Allylpalladium II may serve as an allyl cation if some appropriate nucleophiles are present, regenerating a catalytically active Pd(0) species and [Et.sub.3]B, at the same time, generating one molecule each of an expected allylation product and water.

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In the absence of any nucleophiles, then, [Et.sub.3]B may start to play the second role and promote the exchange reaction of ethyl group and allyl group of the [pi]-allylpalladium II probably through a transition state IV and provide an intermediate III. Along with decomposition of ethylpalladium moiety of III into Pd(0), ethylene and water, III may be converted into allyldiethylborane [2]. That is, through these processes, umpolung of an allyl cation into an allyl anion may be established.

It should be noted that the same catalytic system, Pd(0)-[Et.sub.3]B, works for the generation of both allyl cations and allyl anions. The reaction features completely depend on the reaction partners. When an appropriate nucleophile is present, allyl alcohols work as allyl cations through II. On the other hand, in the absence of nucleophiles and in the presence of electrophiles, allyl alcohols will have an opportunity to work as allyl anions through allylboranes.

GENERATION OF ALLYL CATION

N-Allylation of amines with allyl alcohols takes place readily in the presence of catalytic amounts of Pd[(OAc).sub.2] and [Et.sub.3]B (Scheme 3) [3]. In order to perform the reaction successfully, the choice of phosphine ligand is crucial. For the allylation of aliphatic amines, tributylphosphine is the best ligand. For the allylation of aromatic amines, triphenylphosphine is the best ligand. Under these conditions, we can obtain N-allylation products in excellent yields for a variety of amines.

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C-Allylation of active methylene compounds (diethyl malonate, 2-ethyoxycarbonylcyclohexanone, acetylacetone, 2-acetylcyclohexanone, 2-formylcyclohexanone, etc.) can be performed with similar ease [4]. For example, [alpha]-acetyl-[gamma]-butyrolactone undergoes allylation with parent allyl alcohol and its derivatives bearing substituents [alpha]-, [beta]-, and/or [gamma]-positions (Scheme 4).

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The hexa-allylation of benzenetriol may be of great interest, not only because of the efficiency of the reaction that can be achieved with only 5 mol % of Pd catalyst, but also because of the unique structure of the product (Scheme 5) [5]. This product with high symmetry is rich in double bond and may be used as a linker of polymers and for the synthesis of dendrimers and functional materials.