Dynamic Kinetic Resolution of Axially Chiral Biaryls by Asymmetric Bromination

Key words

dynamic kinetic resolution - polypeptides - biaryls - electrophilic aromatic substitution

Significance

Axially chiral biaryl compounds are tremendously important for organic synthesis. Therefore, catalytic and asymmetric approaches toward this compound class are highly demandable. The authors demonstrate that the dynamic kinetic resolution of biaryl compound 2 can be realized by electrophilic aromatic substitution to afford the non-racemic biaryl 3. To explain the stereoselection of the catalysis, the authors suggest a catalyst-substrate complex in which several amide bonds and the tertiary amine in catalyst 1 participate via multiple hydrogen-bonding interactions.

Comment

Miller and co-workers report an elegant and original approach for the synthesis of optically active biaryl compounds. High selectivity for the desired product (up to 80% yield) and enantio-selectivity (up to 97:3 er) was achieved using tri-peptide catalyst 1. No mono- and dibrominated products were observed. A broad range of substrates are tolerable and include fluorinated as well as heterocyclic compounds.