Halogenated Allyl Alcohol Derivatives ‐ Versatile Electrophiles for Palladium‐Catalyzed Allylic Alkylations

Abstract

Brominated and iodinated allylic substrates can be subjected to palladium‐catalyzed allylic alkylation of amino acid and peptide ester enolates. The incorporation of a vinylic halide functionality into the allylic substrate allows a direct modification of the allylated peptide via cross coupling chemistry. Therefore, the direct introduction of a vinylhalide side chain into a peptide is an interesting alternative to the stannylallylation/halogenation approach. However, the haloallylation is not as trivial as normal allylic alkylations, because the incorporation of a second, competitive electrophilic center into the allyl moiety requires careful optimization of the reaction conditions.

Stereoselective Modification of N-(α-Hydroxyacyl)-glycinesters via Palladium-Catalyzed Allylic Alkylation

“…2-Substituted allyl ethyl carbonates also worked well ( 2ee–2eh ), providing the desired products as single diastereomers. Vinyl bromide 2ei showed the lowest selectivity so far (dr of 90:10), which resulted from epimerization of the more acidic α-center due to the electron-withdrawing bromide . In this case, the reaction had to be quenched at −50 °C to minimize this epimerization.…”