Strecker reaction 1 , the oldest known synthesis of α-aminonitriles, is one of the most general methods potentially useful for syntheses of amino acids and other bioactive compounds including natural products. In addition, the Strecker reaction represents one of the simplest and most economical methods for the preparation of α-amino acids for both laboratory and industrial scales 2 . Since 1850, a number of publications have appeared on this reaction. Still this reaction is under active investigation. Recently, synthesis of hepatitis C virus NS3 serine protease inhibitors 3 , (±)-phthalascidin 622 4 and novel boron-containing retinoids 5 have been reported following this strategy. A number of new catalysts have also been reported for this reaction which includes mesoporous aluminosilicate (Al-MCM-41) 6 , lanthanum(III)-binaphthyl disulfonate 7 , nanocrystalline magnesium oxide 8 , BINOL-phosphoric acid 9 10 , Fe(Cp)₂PF₆ 11 , Jacobsen's thiourea catalyst 12 , N-heterocyclic carbene (NHC)-amidate palladium(II) complex 13 , Yb(OTf)₃-pybox 14 , K₂PdCl₄ 15 , gallium (III) triflate 16 , bisformamides 17 , IBX/TBAB 18 , Lewis base e. g. N,N-dimethylcyclohexylamine 19 , superparamagnetic iron oxide 20 , and ionic liquid 21 . To prepare α-aminonitriles (precursor to α-amino acids) generally an imine is reacted with a cyanide source. Notable among them are HCN 22 , KCN 23 , (EtO)₂P(O)CN 24 25 , Et₂AlCN 26 27 , Bu₃SnCN 28 29 , and TMSCN 3 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 . Among these cyanide sources, trimethylsilyl cyanide (TMSCN) is relatively easy to handle and highly soluble in organic solvents. In contrast, many of these reported methods involve the use of expensive reagents, hazardous solvents, longer reaction times and tedious workup procedure. Therefore, it is desirable to develop an efficient and practical method for the Strecker reaction under eco-friendly conditions.

We have been working on the synthesis and biological evaluation of various β-lactams as novel anticancer agents 30 31 32 33 34 35 over the past several years. The synthesis of β-lactams through imines requires a carbonyl compound and an amine. Our study suggests that carbonyl compounds, amines and TMSCN in the presence of a mild acidic reagent will lead to the synthesis of α-aminonitriles in good to excellent yield. This hypothesis has been tested by reacting several amines with various carbonyl compounds and TMSCN in the presence of indium as catalyst. Recently, organic reactions in water have received much attention in view of green methodologies 36 . First of all, indium and a number of indium salts have been screened using aniline, benzaldehyde and TMSCN as a model reaction at room temperature. The results are shown in Table 1. The reaction was then performed in various solvents using indium as the catalyst to identify the best condition. It suggests that indium is the best catalyst in aqueous medium for the reaction (Table 2). The same reaction was used to optimize the amount of the catalyst. The results show (Table 3) that 10 mol% indium is required to complete the reaction in 30 minutes. Considering the above observations we carried out a series of reaction using various carbonyl compounds, amines and TMSCN in presence of indium (10 mol%) in water as solvent (Figure 1). In all the cases, the reactions were completed within 30 min to 1.5 hr and the products were obtained in excellent yield (Table 4). The products have demonstrated satisfactory spectral and mp data with the reported values.