Rapid access to divergent fused polycycles via one-pot A3 coupling and intramolecular Diels-Alder reaction

Rajashekar Reddy Narra; Vignesh Gopalakrishnan Unnithan; Yifan Liu; Zhihong Guo

doi:10.1002/chem.202401449

Rapid access to divergent fused polycycles via one-pot A3 coupling and intramolecular Diels-Alder reaction

Chemistry. 2024 May 15:e202401449. doi: 10.1002/chem.202401449. Online ahead of print.

Authors

Rajashekar Reddy Narra¹, Vignesh Gopalakrishnan Unnithan¹, Yifan Liu², Zhihong Guo³

Affiliations

¹ The Hong Kong University of Science and Technology, Department of Chemistry, Clear Water Bay, Kowloon, NA, Hong Kong, CHINA.
² The Hong Kong University of Science and Technology, Department of Chemistry, Department of Chemistry, Clearwater Bay, Kowloon, NA, Hong Kong, HONG KONG.
³ The Hong Kong University of Science and Technology, Department of Chemistry, Clear Water Bay, NONE, Kowloon, CHINA.

PMID: 38749918
DOI: 10.1002/chem.202401449

Abstract

Divergent nitrogen-containing fused polycyclic ring systems are constructed from simple starting materials via a one-pot aldehyde-alkyne-amine (A3) coupling and intramolecular Diels-Alder reaction. This domino reaction directly furnishes linear 5/5/5 and 5/5/6, or nonlinear 5/5/6/5, polycyclic rings containing an oxa-bridged fused 5/5 bicycle and a 1,6-enyne substructure. One-step derivation of the oxa-bridged 5/5 bicycle leads to a polyfunctionalized 5/5 bicycle with tetrahydrofuran fused back-to-back to pyrroline or a 6/5 bicycle with the hexahydro-1H-isoindole structure, while cycloisomerizing the enyne substructure adds an extra fused 5-membered ring to afford functionalized linear 5/5/5/5 or 5/5/5/5/5 fused ring systems from selected substrates. In addition, the one-pot product can be designed so that the alkyne moiety is hydroalkoxylated to form an additional heterocyle in a linear 5/5/5/6 or nonlinear 5/5/6/5/5 ring system. This diversity-oriented synthetic approach thus allows rapid access to an under-explored structural space for discovery of new biological or non-biological activities or functions.

Keywords: aldehyde-alkyne-amine (A3) coupling; fused polycycles; heterocycles; intramolecular Diels-Alder reaction; one-pot reaction.