Regiodivergent Synthesis of Methylene and Methyl Ring-Fused Isoquinolinones: Base-Promoted Isomerization of N-Allyl Amides

Li-Yuan Chen; Rong-Shiow Tang; Yang-Chang Wu; Chin-Hung Lai; Ta-Hsien Chuang

doi:10.1021/acs.joc.2c00204

Regiodivergent Synthesis of Methylene and Methyl Ring-Fused Isoquinolinones: Base-Promoted Isomerization of N-Allyl Amides

J Org Chem. 2022 May 6;87(9):5925-5937. doi: 10.1021/acs.joc.2c00204. Epub 2022 Apr 11.

Authors

Li-Yuan Chen¹, Rong-Shiow Tang¹, Yang-Chang Wu², Chin-Hung Lai³, Ta-Hsien Chuang¹

Affiliations

¹ School of Pharmacy, China Medical University, Taichung 406040, Taiwan.
² Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung 404394, Taiwan.
³ Department of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, Taiwan.

PMID: 35404617
DOI: 10.1021/acs.joc.2c00204

Abstract

Methylene and methyl tricyclic isoquinolinones were selectively prepared using a palladium(II)-catalyzed aerobic aza-Wacker reaction, followed by a base- and temperature-controlled Heck reaction catalyzed by palladium(0). Exo- to endo-double-bond migration in isoquinolinones was achieved with 93-99% yields by treatment of the Heck products with Cs₂CO₃ in dimethyl sulfoxide (DMSO) at 150 °C. A probable mechanism for Cs₂CO₃-promoted olefin isomerization was proposed and examined using D-isotope labeling experiments. Finally, yuanamide, a 13-methyl-8-oxoprotoberberine alkaloid, was synthesized using the palladium-catalyzed aza-Wacker/Heck/migration sequence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amides*
Catalysis
Isomerism
Molecular Structure
Palladium*

Substances

Amides
Palladium