Pd/C-Mediated Arylation Followed by I₂-Catalyzed Hydration Strategy: Preparation of Functionalized Novel Indanone Derivatives

Abstract

A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-1-one derivatives has been achieved via Pd/C-mediated arylation followed by I₂-mediated regioselective hydration of 2-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-ones. A wide variety of 3-aryl substituted 2-propynyl indanone derivatives were conveniently prepared by using 10% Pd/C-PPh₃-CuI as a catalyst system, some of which were used to prepare the corresponding ketones via alkyne hydration in the presence of catalytic I₂. In an in vitro study a representative compound showed inhibition of PDE4B (phosphodiesterase type 4B) and binding with this protein in silico

GRAPHICAL ABSTRACT

Keywords:

• Alkyne
• hydration
• indanone
• iodine
• Pd/C

ACKNOWLEDGMENTS

The authors thank Dr. Kishore and his team for PDE4 assay and the management of DRILS for support.

Notes

^a All the reactions were performed using an appropriate iodoarene (0.33 mmol), 10% Pd/C (0.0022 mmol), PPh₃ (0.0086 mmol), CuI (0.022 mmol), alkyne 3 or 4 (0.33 mmol), and Et₃N (0.54 mmol) in EtOH (5 mL) at refluxing temperature under nitrogen.

^b Isolated yields.

^c Corresponding 1,4-dialkynyl benzene derivative was isolated as a side product in this case.

^a All reactions were carried out by using alkyne 5 or 6 (0.15 mmol) and a catalytic amount of iodine (0.015 mmol) in DCM-H₂O (4.9 mL of DCM + 0.1 mL of H₂O) at rt for 24 h.

^b Isolated yields.

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