A novel and highly convenient catalytic variant of the synthesis of a-aminophosphonates on basis of the KabachnikFields reaction [three-component reaction of ketones, diethylphosphite and either benzylamine (series a) of ammonium carbonate (series b)] in the presence of tetra-tert-butylphthalocyanines has been developed. This method affords a-aminophosphonates in acceptable yields for various ketones, including cyclic, sterically hindered and cage ketones. The unsubstituted a-aminophosphonic acids were also obtained from the corresponding esters of series b.a-Aminophosphonic acids may be considered as phosphorous analogues of a-amino acids ('bioisosterism'), 1 and have received considerable attention owing to their pronounced biological activities. These entities have been shown to serve as inhibitors of GABA-receptors, inhibitors of various proteolytic enzymes, inhibitors of dialkylglycine decarboxylase, peptide mimetics, antibiotics, and pharmacological agent, including antitumor, antihypertensive and antibacterial agents. [2][3][4][5][6][7][8][9][10][11][12][13][14][15] Various synthetic methods for a-aminophosphonic acids and a-aminophosphonates have therefore been reported. 5,8,9 However, the classical approach to their synthesis is the Kabachnik-Fields reaction, 10-15 which is a one-pot, three-component operation with carbonyl compound, amine and dialkyl phosphite. This approach is especially satisfactory for reactions with aldehydes, and this protocol was even used for parallel synthesis. 16 In contrast, only a scarce example of the reaction of rather simple ketones (mainly, acetone, acetophenone and cyclohexanone) has been documented. 2,4,7,9 The mechanism of this reaction is still not clearly understood, 12-14 but one of many possible pathways includes nucleophilic addition of phosphites to the transient imines. In fact, reaction of phosphites with imines is really promoted by alkali metal alkoxide or Lewis acids. 17,18 In principle, the Kabachnik-Fields reaction (a three-component process) can also be catalyzed by an acid or base. Indeed, there are also a few examples of catalytic variants of this reaction, and lanthanide triflate/magnesium sulfate, 19 scandium(tris-dodecyl sulfate), 20 lanthanide triflates/ionic liquids 21 and indium(III) chloride 7 were used as the catalysts. The first three examples were satisfactory mainly for aromatic aldehydes; the last one included aliphatic aldehydes and only few ketones. Thus, an efficient procedure for synthesis of a-aminophosphonic acids and aaminophosphonates from ketones, especially hindered ones, is needed.In this report, we describe a novel and efficient catalytic method for the synthesis of a-aminophosphonates and aaminophosphonic acids with the involvement of various ketones. The reactions were performed with diethylphosphite and amines in presence of tetra-tert-butyl-substituted phthalocyanines Pht-1-Pht-3 22 as catalysts. Figure 1 Pht-1 M = AlCl; Pht-2 M = Co(II); Pht-3 M = Ni(II)First, the reaction of 3-methylcyclohexanone, 1, with benzylamine and di...