INTRODUCTION OF ALLYLIC SIDE-CHAINS ONTO PEPTIDES BY PD(0)-CATALYZED ESTER ENOLATE CLAISEN REARRANGEMENT

Allylic esters of peptides undergo an ester enolate Claisen rearrangement upon treatment with LDA in the presence of various metal salts (see Table 1). Best results are obtained using zinc chloride. In the presence of a catalytic amount of Pd(0) the rearrangement products are formed in high yields. Addition of Pd(II) has no significant influence on the yield and stereoselectivity of the reaction. In contrast to the rearrangement without Pd(0) the catalyzed reaction probably proceeds; via intermolecular allylic alkylation as is shown in a cross experiment of different allylic esters. The methodology is not limited to dipeptides, but can also be applied to larger peptides as is illustrated in the rearrangement of tripeptide 11. No epimerization of chiral centers is observed under the reaction conditions used.