Natural Biodegradable Lemon Juice-Catalyzed One-Pot Pseudo-Four-Component Synthesis of Functionally Rich...

The natural nontoxic biodegradable readily available lemon juice-catalyzed eco-friendly one-pot pseudo-four-component reaction strategy of acetylenedicarboxylate, aryl amine, and arylglyoxal synthesizing densely functionalized 4,5-dihydro-1H-pyrrol-5-ols and 1,4-dihydropyridines at room temperature has been disclosed. The switch between 4,5-dihydro-1H-pyrrol-5-ols and 1,4-dihydropyridines could be controlled by the prudent choice of the molar ratio of acetylenedicarboxylate and aryl amine, along with their sequence of addition. Lemon juice exhibited superior catalytic performance from a pool of protic/Lewis acid catalysts, signifying its indispensable role as a proton source, biosurfactant, and bioreductant, enabling the reduction of a keto group to a secondary alcohol on a tethered 1,4-dihydropyridine ring. A wide substrate scope and functional group tolerance offer facile diversity generation. Excellent to quantitative product yields, simple operation and experimental set-up, easy purification bypassing column chromatography, and recoverability/reusability of catalytic lemon juice are distinct advantages. High AE-values and excellent E-factor score endorse the "greenness" of the protocol. The "gram-scale" synthesis and chemical manipulation of the end products to decorated value-added molecules showcase the promising practicality and adaptability of the approach. Several controlled experiments and identification of potential reactive intermediates by ¹H/¹³C NMR and LC-MS analysis allowed us to elucidate the mechanistic route of the reaction strategies.