Functionalized Diphenyl (2-Oxochroman-4-yl)phosphonates: Dual Synthetic Approaches, Mechanistic Insights, and Exploration of a Promising Anti-Lung Cancerous Molecule

Abstract We herein disclose a dual synthetic approach involving room temperature and mechanochemical strategies for a new series of substituted diphenyl (2-oxochroman-4-yl)phosphonates. Both methods offer a practical and straightforward synthetic route for these biorelevant organophosphorus compounds. The salient features of both methods are metal-free synthesis, mild and energy-efficient reaction conditions, good yields with high chemo- and regioselectivity, the avoidance of column chromatographic purification, gram-scale synthetic applicability, and operational simplicity. The density functional theory study provides mechanistic insights into this transformation. Furthermore, biological studies of the synthesized organophosphorus compounds explored their possible anticancer profiles, and among the series, diphenyl (6-(tert-butyl)-2-oxochroman-4-yl)phosphonate (3c) exhibited anti-lung cancer activity in vitro. We herein emphasize that 3c might be considered for preclinical evaluation to establish its therapeutic relevance as an anticancer agent.