To further demonstrate the potential of Ala B in the synthesis of functionalized peptides, we investigated reactions forming macrocyclic oligopeptides (Scheme 5). Cyclic peptides occupy a privileged role due to their propensity to inhibit protein-protein interactions and their ability to permeate cell membranes while remaining resistant to degradation when compared to their acyclic congeners. Direct macrolactamization is the established strategy to form cyclic/stapled peptides, but other disconnections, particularly those that introduce unnatural linkages, need to consider the inherent limitations originating from oligopeptide preorganization. The generality of the transition metal-catalyzed conditions has unlocked a new standard for latestage, chemoselective reactions of peptides. Transition metal-catalyzed reactions can take advantage of C-H activation to overcome the unfavorable cyclization but require specialized directing groups on the N-terminus to guide the sp 3 activation. Based on previous literature precedent we opted for short peptide sequences with 3-bromophenylalanine and Ala B occupying the terminal positions (Scheme 5). We established that during the synthesis of linear peptides 34 and 35, Ala BPai was stable to repeated LiOH saponifications to give the corresponding carboxylic acid that were subsequently elaborated into peptides 34 and 35 (for details, see the SI). These peptides were then subjected to the optimized conditions (Table , entry 14) and furnished 37 in 50-64% yield after HPLC purification. Macrocyclization with Ala BPai from either end of the peptide were equally successful indicating that the attempted substrates show strong conformational bias toward the formation of a macrocycle. This disconnection represents a selective and directing-group-free strategy to introduce disubstituted aryl macrocycles into peptides and further demonstrates the utility of Ala B as a universal building block.