AbstractThe Boc‐protected tripeptides Boc‐Val‐Gly‐Leu‐OH (1), Boc‐Leu‐Sar‐Leu‐OH (2), Boc‐Leu‐Gly‐MeLeu‐OH (3), and Boc‐Val‐BzlGly‐Leu‐OMe (64), tetrapeptide Boc‐Leu‐Gly‐Pro‐Leu‐OH (9), and pentapeptides Boc‐Val‐Leu‐Gly‐Abu‐Ile‐OH (4), Boc‐Val‐Leu‐Sar‐MeAbu‐Ile‐OH (5), Boc‐Val‐Leu‐Gly‐MeAbu‐Ile‐OH (6), Boc‐Val‐Leu‐BzlGly‐BzlAbu‐Ile‐OH (7), and Boc‐Val‐Leu‐Gly‐BzlAbu‐Ile‐OH (8) are prepared by conventional methods (Schemes 4–7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li6derivatives containing glycine, sarcosine orN‐benzylglycine Li enolate moieties (A–H). The polylithiated systems with a dilithium azadienediolate unit (C, F–H) are best generated by treatment witht‐BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)‐configuration (i.e.aD‐amino‐acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i‐PrI, allyl and benzyl bromide, ethyl bromoacetate, CO2, and Me2S2(Schemes 11–13). No epimerizations of the starting materials (racemization of the amino‐acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock‐freezing or by very slow cooling from room temperature to −75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80–95%). The results described are yet another demonstration that peptides may be backbone‐modified through Li