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]CH(3)--C- and [18F]FCH2--C-Containing PET tracers (PET=positron emission tomography).
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 degrees 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 degrees 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.
Doi
Hisashi
H
RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Japan.
Ban
Ikuya
I
Nonoyama
Akihito
A
Sumi
Kengo
K
Kuang
Chunxiang
C
Hosoya
Takamitsu
T
Tsukada
Hideo
H
Suzuki
Masaaki
M
D001896:Boron Compounds / Q000737:chemistry*; D002250:Carbon Radioisotopes / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*
D001896:Boron Compounds; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D006847:Hydrocarbons, Iodinated; D019275:Radiopharmaceuticals; D010165:Palladium