α‐Aminophosphonates are valuable substructures with important biological and pharmacological properties. Lipase catalytic promiscuity is a new method in the organic synthesis for the preparation of α‐aminophosphonates via multicomponent reaction in one pot. This efficient, simple, and eco‐friendly method proceeds in the presence of immobilized Candida Antarctica lipase as catalyst under solvent‐free conditions at room temperature. The new α‐aminophosphonates are synthesized in high yields (up to 96%). Moreover, enzymatic‐catalyzed P–C bond formation through a Kabachnik‐Fields reaction was achieved for the first time.

Nickel (II) sulfate hexahydrate is used for the first time as an efficient catalyst for the one-pot synthesis of a-aminophosphonates by three-component condensation reaction of aromatic aldehyde, primary amine, and diethylphosphite under mild and eco-friendly conditions. NiSO 4 Á6H 2 O was used with a catalytic amount of 5 mol% at room temperature, without solvent in the reaction. A series of the desired aaminophosphonates are obtained after a simple work-up procedure, with excellent yields (up to 92 %) within a short reaction time of 10-20 min in all cases. This heterogeneous catalyst was reused several times with the same activity. The present approach offers the advantages of a clean reaction, simple methodology, easy purification, and economic availability of the catalyst. Graphical Abstract NiSO 4 .6H 2 O 5 mol% Neat, rt 10-20 min R 1 H O + P O OEt OEt + NH 2 R 2 P H N R 1 O OEt OEt R 2 R 1 = Aryl, heteroaryl, ect R 2 = H, CH 3 , CF 3

New bis(α-aminophosphonates) were directly prepared with high diastereoselectivity by lipase catalytic promiscuity in the presence of immobilized Candida antarctica lipase.

Fiaud's acid is used as a novel and effective chiral organocatalyst for bis α-aminophosphonates synthesis with excellent diastereoselectivity and yields within short reaction time. All synthesized bis αaminophosphonates revealed a good to excellent antifungal capacity, where the six compounds 4a, 4b, 4e, 4h, 4k and 4l are the best fungicide inhibiting the growth of Fusarium oxysporum and Botrytis cinerea by 65% to 84% with IC50 values less than 0.02 mg/mL. Similarly, these six products exhibited a strong antioxidant effect, whereas a low inhibition activity was obtained with both AChE and BChE. Furthermore, they displayed a very weak inhibitory activity against tyrosinase except for the compound 4l. These findings suggest a possible use of these compounds as synthetic pesticides with less hazardous effects with antioxidant, and anti-tyrosinase properties.

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