A reinvestigation of mono- and bis-ethynyl phosphonium salts: structural and computational studies and new reactivity

Abstract

A series of mono- and bis-ethynyl phosphonium salts have been prepared via reaction of bromoacetylenes, Ph–C≡C–Br or Br–C≡C–C6H4–C≡C–Br, with various phosphines. Some of the derivatives reported are previously known, ([Ph–C≡C–PPh3]Br, [Ph–C≡C–PMe3]Br, [Ph–C≡C–PBu3]Br, and [Ph3P–C≡C–C6H4–C≡C–PPh3][Br2]), however typically these are missing complete spectroscopic characterization and many have been prepared using much more complicated methods. The derivative [Ph–C≡C–PPh3]Br is capable of inhibiting the growth of tumour cells and has been shown crystallographically to have a significant interaction with the heat shock proteins (HSP70 or DnaK). Thus, solid state structures for all seven phosphonium salts prepared have been reported as they may be of interest to others in this field. Sterically encumbered phosphines such as Mes3P did not react with Ph–C≡C–Br; however, (2,4,6-MeO–C6H2)3P was found to slowly react at moderate temperature to give the expected alkynyl phosphonium salt. However, at higher temperatures, the alkynyl phosphonium undergoes an intramolecular cyclization to form a phosphonium analogue of a 1,4-oxazine. Finally, electronic structure calculations reveal the positive charge on the acetylenic β-carbon, a result of a significant contribution of other canonical structures. The flexibility of the P–C≡C bond has been investigated showing a low-energy barrier (<5 kcal/mol) for bending up to 40° from the optimized angle in the model [Ph–C≡C–PMe3]+ cation. This ease of bending may be of significance in the development of other alkynyl phosphonium tumour cell growth inhibitors.