Highly Selective Preparation of 2-(Hydroxymethyl)vinylphosphonates by Insertion of Ketones into Zirconacycle Phosphonates

Abstract

Three-member zirconacycles insert ketones exclusively at C-2 to give five-member zirconacycle phosphonates that can be hydrolyzed to give 2-(hydroxymethyl)vinylphosphonates, 2, in excellent yields. Other regioisomers were not detected. The reaction works well for both aromatic and aliphatic ketones. Competitive studies indicate that ketones and aldehydes insert at about the same rate and that both react much faster than alkynes. Compounds 2 undergo chlorination with thionyl chloride without rearrangement.

Recently Synthesized Class of Vinylphosphonates as Potent Matrix Metalloproteinase (MMP‐2) Inhibitors

“…The free phosphonic acid compounds 5Ϫ7 were obtained by the hydrolysis of the phosphonate esters by Me 3 SiBr in CH 2 Cl 2 . The other types of 2-(hydroxymethyl)vinylphosphonic acids 8Ϫ14 were obtained by insertion of aldehydes or ketones into the zirconacycle (Scheme 1) and, similarly, were hydrolyzed [28,29]. The 3-oxovinylphosphonic acids 15Ϫ18 were prepared by insertion of acid chlorides into zirconacycles (Scheme 1), followed by similar hydrolysis with Me 3 SiBr [30].…”

Reactions of 1-alkynylphosphonates with group (IV) complexes

“…On the other hand, insertion of ketones into the phosphonate zirconacycles proceeds both with complete stereoand regiospecificity, into C2 of the zirconacycle to provide after hydrolysis 2-(hydroxymethyl)vinylphosphonates, 10 (Scheme 2) [26].…”

“…A possible mechanism involves attack by the Grignard on an intermediate cyclopropene oxide. The sequence is equivalent to syn addition of a Grignard followed by an aldehyde [23,26,27].…”

Molybdenum-Mediated Deconjugation of α,β-Unsaturated Fused-Cyclopentenone Phosphonates

“…[1][2][3] Phosphonates and aminophosphonates have been found to possess chelating properties toward metals, 4 irreversible inhibition properties against serine proteases 5 and the ability to inhibit zinc-dependent enzymes of the metalloprotease family. [6][7][8] As part of ongoing research in our laboratory, we have reported different synthetic methods for the synthesis of novel, highly substituted vinyl phosphonate compounds from 1-alkynylphosphonates using zirconium(II) or titanium(II) reagents, [9][10][11][12][13][14][15][16][17][18][19][20] as well as the synthesis of fusedcyclopentenone phosphonates from 1-alkynylphosphonates via an intramolecular Pauson-Khand reaction 21 using molybdenum hexacarbonyl [Mo(CO) 6 ]. 22 In the course of our research on fused-cyclopentenone phosphonate compounds, 21 we encountered double bond migration.…”