Org. Chem. Front. [SOPhy]

 

Abstract:

The synthesis of natural products containing eight-membered heterocycles has proved to be highly challenging. In this contribution, an environmentally benign synthesis of benzo-1,5 dioxocines via ynamides is reported. A new class of ynamides was prepared by using a green and mild synthetic pathway. The eight-membered heterocycles fused to aryl groups were obtained from propargylic ynamides by treatment with Triton B via addition of enolates to N-allenamide ethers. Deprotonation of the propargylic methylene group occurred before enolization of the methyl ketone because of the polarization of the triple bond by the amide moiety. Regioselective proximal O-alkylation on the N-allenamide provided shelf-stable eight-membered-heterocycles substituted by an amide in an economic fashion with no byproducts. This transformation is applicable to a wide range of ynamides, expanding significantly the chemical space of benzo-1, 5 dioxocines crucial from a drug design perspective.

Graphical abstract:

 

Reference :

Santanu Ghosh, Yongxiang Zheng, Daniele Maccarone, Feven Alemu Korsaye, Ilaria Ciofini,  and  Laurence Miesch 

Triton B-Promoted Regioselective Intramolecular Addition of Enolates to Tethered Ynamides for the Construction of 8-Membered O-Heterocycles

Org. Chem. Front., 2022 – DOI : 10.1039/D2QO00873D

 

Contact:

Laurence Miesch, équipe SOPhy, Institut de Chimie (UMR 7177).