Palladium(0)-Mediated Rapid Methylation and Fluoromethylation on Carbon Frameworks by Reacting Methyl and Fluoromethyl Iodide with Aryl and Alkenyl Boronic Acid Esters: Useful for the Synthesis of [11C]CH3-C- and [18F]FCH2-C-Containing PET Tracers (PET=Positron Emission Tomography)

The rapid methylation and fluoromethylation on aryl and alkenyl carbon frameworks by reacting methyl and fluoromethyl iodide with aryl and alkenyl boronates have been studied with the focus Oil the realization of the synthesis of [C-11]CH3- and [F-18]FCH2- labled positron emission tomography (PET) tracers. The Coupling Of methyl iodide and pinacol phenylboronate (40 equiv) is accomplished in >91% yield. within 5 min at 60 degrees C under the conditions of [Pd-2(dba)(3)]/P(o-CH3C6H4)(3)/K2CO3 (0.5:2:2 dba=dibenzylideneacetone) in DMF. The reaction shows a high generality and is applicable to various types of aryl and alkenyl boronates. giving, the corresponding methylated derivatives in high yields (80-99%). This reaction is also useful for the rapid incorporation of the fluoromethyl group. Thus. this boron protocol provides a firm chemical basis for the synthesis of C-11- and T-incorporated PET tracers and can be used as a complementary method for [C-11]methylation together with our previous and Ongoing processes using organotributylstannanes.