Reactions of 1,2-Oxaphospholene 2-Oxides. 6. Free-Radical and Nucleophilic Substitution at C5: Anomalous Proton-Transfer Behavior of Cyclic Ketals

Article abstract of DOI:10.1021/jo00292a022

The free-radical bromination of 3,5-di-tert-butyl-2-hydroxy-1,2-oxaphosphol-3-ene 2-oxide (1b) with N-bromosuccinimide (NBS) gave the corresponding 5-bromo-3,5-di-tert-butyl-2-hydroxy-1,2-oxaphosphol-3-ene 2-oxide (3) in good yield.Bromide 3 was extremely labile and could not be purified rigorously, but it readily underwent methanolysis to give 3,5-di-tert-butyl-2-hydroxy-5-methoxy-1,2-oxaphosphol-3-ene 2-oxide (7) or hydrolysis to 3,5-di-tert-butyl-2,5-dihydroxy-1,2-oxaphosphol-3-ene 2-oxide (8), both crystalline compounds.Compounds 7 and 8, though somewhat less reactive than 3, were readily interconverted.Treatment of 8 with diazomethane led to dimethyl (Z)-2,2,6,6-tetramethyl-3-oxohept-4-en-5-ylphosphonate (10), indicating that 8 is in equilibrium with its open phosphonic acid isomer.Ketal 7 underwent methoxy exchange at 35.5 deg C with a first-order rate constant of 0.075 m^-1, and the rate was only slightly increased by a large excess of trifluoroacetic acid.The conjugate base of 7 did not undergo exchange.By contrast, 3,5-di-tert-butyl-2,5-dimethoxy-1,2-oxaphosphol-3-ene 2-oxide (11), the methyl ester of 7, was totally inert toward methoxy exchange except in the presence of excess HBr at high temperature for extended periods.The contrasting solvolytic behavior of 7 and 11 under acidic conditions has been interpreted as evidence for an intramolecular proton transfer from an oxygen on phosphorus to the nucleofuge.Ketal-ester 11 underwent slow ring opening in base, which was immediately reversed upon neutralization.The methyl ester (1c) of 1b, the 4-bromo derivative (1d) of 1b, and its methyl ester (1e) all undergo similar reactions with NBS.However, 4,5-dibromide 20 was anomalously unreactive toward nucleophilic substitution.