Preparation of enantiomerically pure (1S,2S)-1-aminocyclopropanephosphonic acid from methylcyclopropanone acetal via spirophosphonate intermediates

Synthesis of Substituted Cyclopropylphosphonates by Michael Induced Ring Closure (MIRC) Reactions

“…They have been prepared as mimics of 1-aminocyclopropane carboxylic acid (ACC) with a high inhibitory activity for the ACC-deaminase and alanine racemase, 1,2 as analogues of (-)-allonorcoronamic acid, 3 as structural moieties of nucleotides, 4 as potential herbicides or plant growth regulators, 5 as potential insecticides, 6 as phosphonic analogues of the antidepressant minalcipran 7 and as constrained analogue of the GABA antagonist phaclophen. 8 Therefore, a variety of methods have been developed to prepare cyclopropylphosphonates such as the phosphonylation of halogenated cyclopropanes, 9 the decomposition of diazophosphonates, 10,11 the cyclopropanation of vinylphosphonates, [12][13][14][15] electrochemical methods, [16][17][18] the addition of phosphites to iminium salts, 19,20 fragmentation and rearrangement of epoxyethylphosphonates, 21 alkylation of benzylphosphonate carbanions with 1,2-dibromoethane 5,22 and the addition of fumarates to phosphonylated sulphonium ylides. 23 On the other hand, the Michael Induced Ring Closure (MIRC) reaction is a well established methodology for the construction of cyclopropanes using several nucleophiles 24 and for cycloalkanes in general.…”

Synthesis methods of (1-aminocyclopropyl)phosphonic acids

“…The use instead of 1-phenylethylamine of aminoalcohol (R)-2-amino-2-phenylethanol resulted in the formation of a mixture (89 : 11) of diastereomers of cyclic aminophosphonates (each of them was a mixture of P*-epimers), which might be separated by chromatography [30] An interesting approach to the synthesis of optically pure (2-methyl-1-aminocyclopropyl)phosphonates from racemic acetal 2-methyl-1-methoxy-1-trimethylsilyloxycyclopropane is described in [29] based on the chromatographic separation of diastereomeric racemate of N-formylated trans-isomers of diethyl or diisopropyl (1S*,2S*,1'S)-[2-methyl-1-(1-phenylethylamino)cyclopropyl]phosphonates (Scheme 6).…”

Asymmetric Synthesis of Tetrasubstituted α-Aminophosphonic Acid Derivatives

“…Following the same approach, Faldel’s group described later the synthesis of spirocyclic α-aminophosphonates 70 ( Scheme 14 ) [ 48 ]. Starting also from silylated acetal 64 , deprotected acetal intermediate 66 is again formed by an alcoholysis and then, iminium species 72 is obtained by reaction with ( R )-phenylglycinol under acidic conditions.…”