2-Phosphonato-2-cycloenone and cyclopropylphosphonates : synthesis and utilization

Abstract

2-Phosphonato-2-cycloenones were synthesized via one-pot ozonolysis-aldol condensation in good yield, which are the first examples of cyclic vinylphosphonates containing oxo group at a-position as an electron withdrawing group. It was found that phosphonato group at 2-position in 2-cycloenone could induce copper-free conjugate addition of naked alkyl lithium or Grignard reagents, that is 2-phosphonato-2-cycloenones could be used as activated Michael acceptors. β-Ketophosphonates were bis-alkylated using 1,4-dibromo-2-butene to yield 1- acyl-2-vinylcyclopropylphosphonates, which are expected to be useful as 1,2-difunctionalized cyclopropylphosphonates. γ,δ-Epoxyphosphonates were synthesized via allylation with subsequent epoxidation. Base promoted epoxide opening reaction of these compounds gave trans-hydroxymethylcyclopropylphosphonates in good yield and in good stereo-selectivity. Resulting compound was successfully used to prepare cyclopropylphosphonate analogue of nucleotide phosphate, via Mitsnobu reaction, which are the first example among the series of phosphonates analogues of nucleotide phosphates.