Premium
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 [ 11 C]CH 3 C‐ and [ 18 F]FCH 2 C‐Containing PET Tracers (PET=Positron Emission Tomography)
Author(s) -
Doi Hisashi,
Ban Ikuya,
oyama Akihito,
Sumi Kengo,
Kuang Chunxiang,
Hosoya Takamitsu,
Tsukada Hideo,
Suzuki Masaaki
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200801974
Subject(s) - methyl iodide , chemistry , aryl , pinacol , iodide , boronic acid , methylation , palladium , medicinal chemistry , organic chemistry , catalysis , biochemistry , alkyl , gene
A new synthetic methodology for the rapid methylation and fluoromethylation on aryl and alkenyl frameworks by using methyl and fluoromethyl iodide with an organoboronic acid ester has been developed under the simple and mild conditions of [Pd 2 (dba) 3 ]/P( o ‐CH 3 C 6 H 4 ) 3 /K 2 CO 3 (dba= dibenzylideneacetone) in DMF at 60 °C for 5 min (see scheme). This boron protocol provides a firm chemical basis for the synthesis of 11 C‐ and 18 F‐incorporated PET tracers.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 on the realization of the synthesis of [ 11 C]CH 3 ‐ and [ 18 F]FCH 2 ‐labeled 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 °C under the conditions of [Pd 2 (dba) 3 ]/P( o ‐CH 3 C 6 H 4 ) 3 /K 2 CO 3 (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 11 C‐ and 18 F‐incorporated PET tracers and can be used as a complementary method for [ 11 C]methylation together with our previous and ongoing processes using organotributylstannanes.