On the rearrangement of N-aryl-N-Boc-phosphoramidates to N-Boc-protected o-aminoarylphosphonates

Abstract

Various arylamines were converted in two steps to N-Boc-N-arylphosphoramidates. LiTMP and LDA induced directed ortho-metalation at temperatures from −78 to 0 °C. The ensuing [1,3]-migration of the phosphorus atom with its substituents from the nitrogen to the ortho-carbanionic carbon atom gave N-Boc-protected o-aminoarylphosphonates. The nature of the substituent of 3-substituted phenylphosphoramidates strongly influenced the regioselectivity of phosphonate formation. A crossover experiment with a deuterated phosphoramidate proved the intramolecular course of the rearrangement. Three representative N-Boc-o-aminoarylphosphonates were deprotected to access the corresponding o-aminoarylphosphonic acids.Graphical Abstract

Inositol Adenophostin: Convergent Synthesis of a Potent Agonist of d-myo-Inositol 1,4,5-Trisphosphate Receptors

“…N -Phosphoramidates can be hydrolyzed using strongly acidic, − strongly basic, or metallic reagents . Hydrogenation of N -phosphate benzyl ester generated partially deprotected phosphoramidate that could be further converted to the fully deblocked free amino compound under controlled mild acidic conditions .…”