SYNTHESIS OF DIASTEREOMERICALLY PURE 1-AMINOCYCLOPROPYLPHOSPHONIC ACIDS

The lithium or potassium derivative of diethyl isocyanomethylphosphona te (1) reacts with epoxides in the presence of boron trifluoride-dieth yl ether to provide the diethyl 3-hydroxy-1-isocyanoalkylphosphonates rac-3. The corresponding mesylates rac-4 undergo a base-mediated cycli zation to the diethyl 1-isocyanocyclopropylphosphonates rac-5. Acidic hydrolysis affords the diethyl 1-aminocyanocyclopropylphosphonates rac -6, which upon treatment with trimethylsilyl iodide yield the 1-aminoc yclopropylphosphonic acids rac-7. A base-mediated cycloalkylation of 1 with dibromoalkanes 10 gives the diethyl 1-isocyanocycloalkylphosphon ates 11, which are suitable precursors for the achiral 1-aminocycloalk ylphosphonic acids.