Direct Asymmetric Functionalization of α‑Amino C–H Bonds

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.

Publication History

Article published online:
21 November 2024