Zhang R,
Xu J,
Liu S,
Si S,
Chen J,
Wang L,
Chen W-W,
*
Zhao B.
*
Shanghai Normal University, P. R. of China
Direct Enantioselective α-C−H Conjugate Addition of Propargylamines to
α,β-Unsaturated Ketones via Carbonyl Catalysis.
J. Am. Chem. Soc. 2024;
146: 25927-25933
DOI:
10.1021/jacs.4c09840
Keywords
organocatalysis - conjugate addition - propargylamines - cyclization - 1-pyrrolines - biomimetic catalysis
Significance
The Zhao group presents a direct asymmetric α-C−H conjugate addition of
NH2-unprotected propargylamines to α,β-unsaturated ketones by using a
chiral pyridoxal catalyst. The reaction provides a wide range of chiral alkynyl
1-pyrrolines bearing two contiguous stereocenters in good yields, with excellent
diastereo- and enantioselectivities. This work furnishes a streamlined approach for
accessing pyrroline-containing pharmaceuticals.
Comment
Direct asymmetric functionalization of the poorly reactive α-C−H bonds of
NH2-unprotected propargylic amines poses a significant challenge in
chemical synthesis. First, the low acidity (pK
a ~ 42.6) of the
α-C−H bond makes it difficult to deprotonate (Angew. Chem. Int. Ed.
2022, 61, e202206111). Second, classical N-addition may interfere with
the overall reaction. Third, the highly reactive alkynyl group also has the
potential to disrupt the transformation.
