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 β‐dimethylaminoalanine (Dmaa) are capable of atroposelectively coupling naphthols and ester‐bearing quinones to yield non‐C2‐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. Two become one: A peptide‐catalyzed approach for the atroposelective coupling of naphthols and ester‐bearing quinones to access non‐C2‐symmetric BINOL‐type scaffolds is presented. The reaction gives good yields and enantioselectivity, and a diastereoselective functionalization of a naproxen analogue highlights the utility of this system.