Convenient synthesis of propane aminophosphonic acids, aminodiphosphonic acids and their structural analogues, mediated by azetidinium salts

The reactions of azetidinium salts with phosphorus nucleophiles R2P(O)H hav e been investigated. Treatment of O-benzyl-N,N-diethyl-3-hydroxyazetidinium salt 2 with R2P(O)H in the presence of sodium hydride gave the correspondi ng gamma-N,N-diethylamino-beta-benzyloxypropylphosphonate 6a or phosphine o xide 6b. After debenzylation gamma-N,N-diethylamino-beta-hydroxypropylphosp honate 3a and phosphine oxide 3b were obtained. The compound 6a was convert ed into its sulfonate ester 8 which underwent elimination to yield 4. The s tructure 4 has been employed in Michael addition of R2P(O)H to form compoun ds 5 containing two phosphorus centers. Further compounds of type 3 have be en transformed into compounds 5 by reaction with R2P(O)H in the presence of 1.1 equivalents of NaH in boiling toluene. Finally, azetidinium salts 1 ha ve been converted into compounds 5a by reaction with two equivalents of R2P (O)H in the presence of 2.1 equivalents of NaH. Molecular mechanics with im plementation of the Allinger MM2 force field and semiempirical AM1 and PM3 methods were used to investigate structures 5d and 5f. (C) 1999 Elsevier Sc ience Ltd. All rights reserved.