Inhibitory effects of the guanine moiety on Suzuki couplings of unprotected halonucleosides in aqueous media.
In the Suzuki arylations of unprotected halonucleosides in aqueous media, 8-bromo-2'-deoxyguanosine (8BrdG) couplings were slower to reach completion than the corresponding 8-bromo-2'-deoxyadenosine (8BrdA) couplings. The guanine moiety has an acidic proton, which under our Suzuki conditions (pH congruent with 10) may be deprotonated to give an anion that can coordinate to palladium. The possibility that guanine coordination was responsible for the observed slower rates was explored using additive experiments in which nonhalogenated nucleosides were added to the Suzuki coupling reaction of 8BrdA or 4-bromotoluene and PhB(OH)2 and the reaction progress monitored by HPLC or GC. Adding dG slowed these reactions, and an induction period was observed. The addition of dA or 1-methyl-2'-deoxyguanosine (1MedG) to these couplings did not affect the rate of conversion to product. Guanine coordination was further explored using 13C and 31P NMR spectroscopy, which implies that guanine is coordinating to palladium through N-1 or O-6, or both. Furthermore, the presence of dG inhibited the formation of the active palladium(0) catalytic species, which may account for both the observed induction period and the sluggishness of reactions where guanine is involved.
Western
Elizabeth C
EC
Department of Chemistry and the Center for Green Manufacturing, The University of Alabama, Box 870336, Tuscaloosa, Alabama 35487-0336, USA.
Shaughnessy
Kevin H
KH
D000838:Anions / Q000737:chemistry; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D006147:Guanine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry; D010720:Phosphines / Q000737:chemistry; D012995:Solubility; D013696:Temperature; D014867:Water / Q000737:chemistry*
D000838:Anions; D008024:Ligands; D009705:Nucleosides; D010720:Phosphines; D014867:Water; D010165:Palladium; D006147:Guanine; C044646:phosphine