Asymmetric Halogenation-Semipinacol Rearrangement

Significance

Tu and co-workers report a highly stereoselective halogenation-semipinacol rearrangement reaction catalyzed by cinchona alkaloid derivatives. Both (DHQD)₂PYR and (DHQ)₂PYR show remarkable efficiency to afford both enantio­mers in excellent enantioselectivity. β-Bromo ­ketones were obtained by using 1 as a halogen source, and β-chloro ketones could be prepared with hydantoin derivatives 2 as the chlorine source. Substituting the achiral acid additive, 4-methoxybenzoic acid, by a chiral N-protected amino acid is beneficial in terms of enantioselectivity without significant match/mismatch effect. Electron-poor substrates undergo the halogenation-rearrangement sequence with good to excellent enantioselectivity albeit lower chemical yields.