TOWARDS ROBUST CONDITIONS FOR IRIDIUM-MEDIATED EXCHANGE

摘要

As a method for isotopic labelling, iridium-mediated hydrogen exchange suffers from problems with transferability between laboratories. In addition, there is still no good general catalyst for exchange in homologous substrates such as benzyl ketones and phenylacetamides. This presentation describes some of our recent efforts to understand and overcome the former, and to develop better catalysts for the latter.Many of the problems encountered with unexpectedly low levels of exchange prove, in effect, to be a consequence of the slowing of exchange as a result of a low partial pressure of tritium in the system, a low concentration of the exchange solution, or partial poisoning of the catalyst by a coordinating solvent such as water. This effect in turn appears to be related to degradation of the active catalyst within a relatively short time. This is illustrated (Figure 1) by the kinetics of deuteration of acetophenone in the presence of Ir(cod)(PPh_3)_2~+ and Ir(cod)(PPh_3)_3~+:whereas exchange with the former stops abruptly within four hours, the latter remains active until exchange is complete. Separate NMR studies have shown that the hydrogenated form of Ir(cod)(PPh_3)_2~+ is stable in solution for an extended period.