The study of metal-free and palladium-catalysed synthesis of benzochromenes via direct C–H arylation using unactivated aryl benzyl ethers derived from essential oils as raw materials

Marlyn C Ortiz Villamizar,Leonor Y Vargas Méndez,Vladimir V Kouznetsov,Carlos E Puerto Galvis,Fedor I Zubkov

doi:10.1039/c7qo00232g

Abstract

The synthesis of 6H-benzo[c]chromenes, from phenol-rich essential oils, was studied through two approaches, establishing the Pd-approach as the most efficient protocol over the metal-free process.

Highlights

The 6H-benzo[c]chromene ring has recently emerged as one of the most privileged scaffolds and an important substructure within the modern drug discovery field.[1,2] This heteroaromatic system is present in many natural products, such as pulchrol 1 and pulchral 2, both isolated from the plant Bourreria pulchra and possessing interesting antiprotozoal activities towards Leishmania mexicana and Trypanosoma cruzi, especially 1.3 While the Δ9-tetrahydrocannabinol 3, cannabinol 4 (Cannabis sativa) and the didehydroconicol 5
With the knowledge that t-BuOK has recently promoted the synthesis of some 6H-benzo[c]chromenes from iodine and bromide aryl benzyl ethers,[17] and inspired the synthesis of phenanthridines from N-(2-chloroaryl)benzoimines mediated by t-BuOK and ethylene glycol as a ligand,[18] suggests that chlorine derivatives could favour the formation of aryl radical species during the reaction critical step,[19] despite the low dissociation energy of the C–Cl bond.[20]
We envisioned that chloride aryl benzyl ether 8a could be a good substrate for the model homolytic aromatic substitution (HAS) reaction

Summary

Introduction

The 6H-benzo[c]chromene ring has recently emerged as one of the most privileged scaffolds and an important substructure within the modern drug discovery field.[1,2] This heteroaromatic system is present in many natural products, such as pulchrol 1 and pulchral 2, both isolated from the plant Bourreria pulchra and possessing interesting antiprotozoal activities towards Leishmania mexicana and Trypanosoma cruzi, especially 1.3 While the Δ9-tetrahydrocannabinol 3, cannabinol 4 (Cannabis sativa) and the didehydroconicol 5

Results

Conclusion