Interrupted Aza-Wittig Reactions Using Iminophosphoranes to Synthesize 11C-Carbonyls

Abstract

Iminophosphoranes are reported as convenient precursors to amides, ureas, carbamates and other carbonyl-containing molecules through CO2-fixation. Key to this transformation with stable isotopes and carbon-11 is interception of the reactive isocyanate intermediate. Automated synthesis and isolation of PET radiopharmaceuticals is achieved.

[11C]CO2 BOP fixation with amines to access 11C‐labeled ureas for PET imaging

“…5 Consequently, several 11 C-labeled urea tracers with attractive biological properties have been developed for PET (Figure 1A). [6][7][8][9][10][11][12][13][14] Various synthetic methodologies have been reported for their synthesis over the years (Figure 1B). While there were initial reports regarding the synthesis of 11 C-labeled ureas, [15][16][17][18][19][20] the interest for their synthesis significantly increased around 2006.…”

“…This method was later implemented by Ismailani et al who used the aza-Wittig reaction in combination with DBU. 10 An advantage of these methods is that no symmetrical urea side products are obtained; however, phosphinimides have limited commercial availability, which requires synthesis of suitable precursors prior to their use in radiosynthesis. Finally, an intramolecular Staudinger aza-Wittig reaction has been reported for the synthesis of 11 C-labeled asymmetric ureas from [ 11 C]CO 2 using azide and amine precursors.…”

“…A method that does not require harsh dehydrating agents was reported by van Tilburg et al 31 who reacted a phosphinimide with [ 11 C]CO 2 via an aza‐Wittig reaction. This method was later implemented by Ismailani et al who used the aza‐Wittig reaction in combination with DBU 10 . An advantage of these methods is that no symmetrical urea side products are obtained; however, phosphinimides have limited commercial availability, which requires synthesis of suitable precursors prior to their use in radiosynthesis.…”