Hou C,
Peng B,
Ye S,
Yin Z,
Cao J,
Xiao X,
Zhao B.
*
Shanghai Normal University, P. R. of China
Catalytic Asymmetric α C(sp
3)–H Addition of Benzylamines to Aldehydes.
Nat. Catal. 2022;
5: 1061-1068
DOI:
10.1038/s41929-022-00875-3
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.
