Chiral Pyridoxal–Gold Rush in Asymmetric Carbonyl Catalysis

Key words

biomimetic catalysis - C–H functionalization - carbonyl catalysis - chiral pyridoxal - β-aminoalcohols - benzylamines - squaramide

Significance

Although previously reported by Zhao et al. (Angew. Chem. Int. Ed. 2022, 61, e202206111), an evolving enantioselective version of activating the C(sp³)–H bond of free NH₂ benzylamines is developed. Using a squaramide-modified chiral pyridoxal catalyst, the organocatalytic asymmetric α-C–H addition of benzylamines to aldehydes provided access to chiral syn-β-aminoalcohols in moderate to high yields with excellent dia­stereo- and enantioselectivities.

Comment

One of the big challenges in the pyridoxal catalysis is the control of stereoselectivity. The squaramide moiety, introduced in the side chain of the pyridoxal catalyst, both activates and orients the electrophilic aldehyde through hydrogen bonding. As a kind of late bloomer, pyridoxal catalysis have been developed more slowly than other activation modes of organocatalysis but is now delivering amazing chemistry.