Pd0-mediated rapid coupling of methyl iodide with excess amounts of benzyl- and cinnamylboronic acid esters: efficient method for incorporation of positron-emitting 11C radionuclide into organic frameworks by coupling between two sp3-hybridized carbons

Evaluation of TlOH Effect for Pd<sup>0</sup>-Mediated Cross-Coupling of Methyl Iodide and Excess Boronic Acid Ester toward Fabrication of [<sup>11</sup>C]CH<sub>3</sub>-Incorporated PET Tracer

“…Such a strong base may also be detrimental for base-sensitive substrates. The results presented herein serve as a confirmation that the conditions described in our previous Pd 0 -mediated rapid C-methylation studies [5][6][7][8] are currently the most efficient [3,9]. The four novel types of rapid C-methylations discussed above are potential groundbreaking methods for fabricating short-lived 11 C-incorporated PET probes for in vivo molecular imaging studies in both animals and humans.…”

“…For the actual PET tracer synthesis, we set up a model reaction using excess boronic acid pinacol ester for methyl iodide (40 equiv) [6][7][8]. The reaction time was fixed at 5 min, which is similar to our previous studies using organoborane compounds [7,8].…”

“…The reaction time was fixed at 5 min, which is similar to our previous studies using organoborane compounds [7,8]. First, we attempted Kishi's conditions that involve the reaction of phenylboronic acid pinacol ester (1a) under CH 3 I/1a/[Pd{P(C 6 H 5 ) 3 } 4 ]/ TlOH (1:40:1:3) in 90:10 THF/H 2 O at RT for 5 min [3].…”

“…Four types of rapid cross-coupling reactions (rapid C- [ 11 C]methylations) were developed for arene, alkene, alkyne, and alkane frameworks using [ 11 C]methyl iodide and excess amounts of organostannyl and organoborane substrates [5]. Pd 0 -mediated Suzuki-Miyaura-type rapid C-methylations were conducted using methyl iodide and a phenyl- [6], an alkenyl- [7] a benzyl- [8], or a cinnamylboronic acid ester [8] 3 and CsF. These conditions are superior to the method using [Pd(dppf)Cl 2 ] (dppf = 1,1'-bis(diphenylphosphino)ferrocene) and K 3 PO 4 under microwave heating [9].…”

Efficient syntheses of [11C]zidovudine and its analogs by convenient one‐pot palladium(0)–copper(I) co‐mediated rapid C‐[11C]methylation

“…Recently, for syntheses of 11 C‐labeled PET tracers, four types of rapid C ‐[ 11 C]methylation methods (sp–sp 3 , sp 2 (alkenyl)–sp 3 , sp 2 (arenyl)–sp 3 , and sp 3 –sp 3 couplings) were developed, using the Pd(0)‐mediated rapid reaction of [ 11 C]CH 3 I with organoboron or organostannyl precursors . When organostannyl compounds were used as precursors, copper(I) salt was used in combination to activate the precursors.…”