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

The success of this nucleophilic allylation may owe its origin to the low acidity of [alpha]-H of aldimines (as compared with that of aldehydes) and high reactivity of allylborane toward aldimines. As is apparent from Scheme 13, the reaction is applicable to aromatic aldehydes, unsaturated aldehydes, and secondary aldehydes. However, not surprisingly, primary aldehydes (e.g., dihydrocinnamaldehyde) showed marginal success.

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Lactol forms primary aldimine by exposure to p-anisidine (Scheme 14). In contrast to the aldimine of dihydrocinnamaldehyde discussed in Scheme 13, this particular primary aldimine behaved nicely and provided the expected homoallylamine in reasonable yield [20]. Furthermore, the reaction showed high stereoselectivity. Especially, [alpha]-phenylallyl alcohol showed high selectivity and provided syn-isomer exclusively.

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This stereoselectivity may be rationalized by supposing a six-membered chair-like transition state (Scheme 14). This transition state is characterized by an equatorial orientation of phenyl group and diaxial orientation of both substituents of trans-aldimine. Diequatorial orientation of both substituents of trans-aldimine may be prohibited by gauche repulsion between PMP and two ethyl groups on boron.

The reaction can be extended to the allylation of aldimines of ribose and deoxyribose (Scheme 15) [20]. Although the yields are not very good at the moment, this reaction may be synthetically useful, because the reaction can be performed without protection of polyhydroxy functional groups.

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GENERATION OF ZWITTERIONIC TRIMETHYLENEMETHANE

As mentioned in Scheme 9, in the presence of [Et.sub.3]N and LiCl, one of the allyl alcohol moieties of 2-methylene-1,3-propanediol serves as an allyl cation and reacts with cyclohexanecarbaldehyde to provide the [alpha]-allylation product in good yield (Scheme 16).

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On the other hand, in the absence of these additives under otherwise the identical conditions, the remaining allyl alcohol moiety undergoes nucleophilic allylation upon aldehyde carbonyl carbon to provide 3-methylenecyclopentanol in good yield [18,21].

If the [alpha]-hydrogen of aldehyde is acidic enough, and hence electrophilic allylation proceeds much faster than nucleophilic allylation, we need not use [Et.sub.3]N and LiCl any more. So, we can perform electronically opposite electrophilic and nucleophilic allylations in one-pot. For example, [alpha]-phenylpropionaldehyde and [alpha],[alpha]-diphenylacetaldehyde reacted with 2-methylenepropane-1,3-diol in one-pot and provided the expected products in good yield (Scheme 17).

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This amphiphilic activation reaction might remind one of Trost's trimethylenemethane-palladium chemistry [22] and Yamamoto's bis-[pi]-allylpalladium chemistry [23], especially Trost's, because these two reactions provide structurally similar type products sharing methylenecyclopentane skeleton (Scheme 18).