Peptide-Catalyzed Fragment Couplings that Form Axially Chiral Non-C2-Symmetric Biaryls

We have demonstrated that small, modular, tetrameric peptides featuring the Lewis-basic residue beta-dimethylaminoalanine (Dmaa) are capable of atroposelectively coupling naphthols and ester-bearing quinones to yield non-C-2-symmetric BINOL-type scaffolds with good yields and enantioselectivity. The study culminates in the asymmetric synthesis of backbone-substituted scaffolds similar to 3,3 '-disubstituted BINOLs, such as (R)-TRIP, with good (94:6 e.r.) to excellent (>99.9:0.1 e.r.) enantioselectivity after recrystallization, and a diastereoselective net arylation of the minimally modified nonsteroidal anti-inflammatory drug (NSAID) naproxen.