Exploration of the labeling of [ 11 C]tubastatin A at the hydroxamic acid site with [ 11 C]carbon monoxide

We aimed to label tubastatin A (1) with carbon‐11 ( t 1/2  = 20.4 min) in the hydroxamic acid site to provide a potential radiotracer for imaging histone deacetylase 6 in vivo with positron emission tomography. Initial attempts at a one‐pot Pd‐mediated insertion of [ 11 C]carbon monoxide between the aryl iodide (2) and hydroxylamine gave low radiochemical yields (<5%) of [ 11 C]1. Labeling was achieved in useful radiochemical yields (16.1 ± 5.6%, n  = 4) through a two‐step process based on Pd‐mediated insertion of [ 11 C]carbon monoxide between the aryl iodide (2) and p ‐nitrophenol to give the [ 11 C] p ‐nitrophenyl ester ([ 11 C]5), followed by ultrasound‐assisted hydroxyaminolysis of the activated ester with excess hydroxylamine in a DMSO/THF mixture in the presence of a strong phosphazene base P 1 ‐t‐Bu. However, success in labeling the hydroxamic acid group of [ 11 C]tubastatin A was not transferable to the labeling of three other model hydroxamic acids.