Chelated enolates of amino acid esters - New and efficient nucleophiles for isomerization-free, stereoselective palladium-catalyzed allylic substitutions

Chelated amino acid ester enolates were found to be suitable nucleophiles f or palladium-catalyzed allylic alkylations. Unlike stabilized soft nucleoph iles, the chelated enolates react under very mild reaction conditions, even at -78 degreesC. If TFA-protected amino acid tert-butyl esters are used as nucleophiles, the anti-configured products are obtained in a highly diaste reoselective fashion. This protocol is therefore a good supplement to the c helate enolate Claisen rearrangement, which gives rise to the corresponding syn products. Especially good results are obtained with allylic carbonates as substrates, as these are readily able to form the required pi -allylpal ladium complexes at temperatures as low as -78 degreesC. In this temperatur e range, pi-sigma-pi isomerization of the n-allyl intermediates does not pl ay a significant role, and so application of the highly reactive chelated e nolates allows the use of C-nucleophiles in allylic alkylation of (Z)-allyl substrates with complete conservation of the olefin geometry for the first time. With (Z)-allyl carbonates bearing two identical substituents at the allyl termini, the attack of the nucleophile on the intermediate pi -allylp alladium complex occurs exclusively at the anti position, giving rise to th e (E)-configured substitution product, If optically active allyl carbonates are used, complete transfer of the chirality to the product is observed. T hese examples clearly indicate that the in-a-it isomerization is completely suppressed under the reaction conditions used. This opens up new synthetic applications, which will be evaluated in the near future.