Indium trichloride catalyzed one-step synthesis of a-amino nitriles by a three-component condensation of carbonyl compounds, amines and potassium cyanide Brindaban C. Ranu, p Suvendu S. Dey and Alakananda Hajra Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta 700 032, India Received 16 November 2001; accepted 7 February 2002 Abstract ÐA simple and general method has been developed for the synthesis of a-aminonitriles by a one-pot three-component condensa- tion of aldehydes or ketones, amines and potassium cyanide in THF in presence of a catalytic amount of indium trichloride. q 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction The synthesis of a-amino nitriles has been the subject of considerable current interest as these molecules serve as useful intermediates towards preparation of a-amino acids. 1 The classical procedure, known as the Strecker reaction for their synthesis involves the treatment of an aldehyde or a ketone with alkaline cyanides and salts of amines, and was discovered a century and a half ago. 2 The reaction is usually carried out in aqueous solution and the work-up procedure is also tedious. Thus, several modi®ca- tions of the Strecker reaction have been reported 3 using a variety of cyanide reagents, such as a-trimethylsiloxy- nitriles, 3b diethyl phosphorocyanidate, 3a under different reaction conditions. However, many of these reagents are not easily accessible due to their high cost and thus there is a need for a more simple, straight-forward and cost-effective method for the synthesis of these useful compounds. Recently, indiumIII) chloride has emerged as a powerful Lewis acid catalyst in a variety of organic transformations. 4 Our own work 5 also found InCl 3 to be a very ef®cient catalyst for two and three component condensation reaction involving addition of a nucleophile to the imine generated in situ from a carbonyl compound and an amine. This prompted us to explore the addition of a cyanide ion to an imine under indiumIII) chloride catalysis and we have discovered an excellent modi®cation of the Strecker synthesis by a one-pot procedure Scheme 1). 2. Results and discussion In a typical general procedure, a mixture of a carbonyl compound aldehyde or ketone), an amine and potassium cyanide in THF was stirred for aldehydes) or re¯uxed in case of ketones) in presence of indiumIII) chloride 30 mol%) for a certain period of time TLC). Extraction with ether and puri®cation by column chromatography over silica gel furnished the pure product. A wide range of struc- turally varied aldehydes and ketones were coupled with a variety of aliphatic and aromatic amines and potassium cyanide by this procedure through a single step operation to produce the corresponding a-amino nitriles. The results are summarized in Table 1. It was found that aldehydes, in general, including aromatic, aliphatic and heterocyclic units participate readily using this procedure, whereas only cyclic ketones produced satisfactory results. Acyclic ketones largely remained inert; longer reaction times and greater amounts of indium trichloride also failed to make a signi®- cant improvement. Conjugated aldehydes and ketones react by this procedure to furnish mainly tarry material. On the other hand, aliphatic and aromatic primary amines and cyclic secondary amines like pyrrolidine and morpholine are readily coupled. Although the amount of catalyst has been optimized to 30 mol%, lesser amount 10±20 mol%) also worked with longer reaction times. In general, the reactions are considerably fast. No undesired side product was isolated. The yields are reasonably good for a three- component coupling reaction. Notably, this reaction has Tetrahedron 58 2002) 2529±2532 Pergamon TETRAHEDRON 0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII: S0040-402002)00132-1 Keywords: a-amino nitriles; one-pot three-component condensation; indium trichloride. p Corresponding author. Tel.: 191-033-4734971; fax: 191-033-4732805; e-mail: ocbcr@mahendra.iacs.res.in Scheme 1.