Palladium‐Catalyzed β‐C(sp 3 )‐H Arylation of Alanine at the Internal Position of Peptides

Late‐stage peptide modification by C–H functionalization has been extensively investigated in the past decades. However, transition metal‐catalyzed C(sp 3 )‐H functionalization of amino acid residues at the internal positions of peptides remains underdeveloped due to the inhibition effect of peptide bonds (secondary amide). In the context, we herein report a backbone protection strategy, which enabled Pd‐catalyzed β‐C(sp 3 )‐H arylation of internal alanine in peptides. Control experiment demonstrated that the backbone protecting group ( p ‐methoxybenzyl, PMB) not only controlled the position‐selectivity, but also improved the reactivity of C–H arylation. Further removal of the protecting group under mild and oxidative conditions to afford the backbone‐unprotected peptides efficiently exhibited the synthetic utility of the developed protocol.