Rapid methylation on carbon frameworks useful for the synthesis of 11CH3-incorporated PET tracers: Pd(0)-mediated rapid coupling of methyl iodide with an alkenyltributylstannane leading to a 1-methylalkene.
The Pd(0)-mediated rapid coupling of methyl iodide with an excess of alkenyltributylstannane was examined with the aim of incorporating a short-lived 11C-labeled methyl group into a biologically significant organic compound with a 1-methylalkene unit for the synthesis of a PET tracer. Four sets of reaction conditions (A-D) were used, all performed in DMF at 60 degrees C for 5 min. Condition B, using CH3I/stannane/Pd2(dba)3/P(o-tolyl)3/CuCl/K2CO3 (1:40:0.5:4-6:2:5), works well in almost all cases. Condition D, using CH3I/stannane/Pd2(dba)3/P(o-tolyl)3/CuX (X = Br, Cl, or I)/CsF (1:40:0.5-5:2-20:2-20:5-50), shows the best results with regard to general applicability to tin substrates, affording the corresponding methylated product in >90% yield based on consumption of methyl iodide. P(t-Bu)2Me was less effective than P(o-tolyl)3, particularly for alpha,beta-unsaturated carbonyl substrates. No regio- or stereoisomerization occurred under these reaction conditions. The efficiency of the protocol was demonstrated by synthesis of an 11C-methylated compound.
Hosoya
Takamitsu
T
Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu, 501-1194, Japan.
Sumi
Kengo
K
Doi
Hisashi
H
Wakao
Masahiro
M
Suzuki
Masaaki
M
D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000295:instrumentation*; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000737:chemistry*; D024482:Vitamin K 2 / Q000737:chemistry
D000475:Alkenes; D006847:Hydrocarbons, Iodinated; D014220:Trialkyltin Compounds; D024482:Vitamin K 2; D010165:Palladium; D002244:Carbon; C014055:methyl iodide