Pd(0)/Cu(I)-Mediated Direct Arylation of 2′-Deoxyadenosines: Mechanistic Role of Cu(I) and Reactivity Comparisons with Related Purine Nucleosides was written by Storr, Thomas E.;Baumann, Christoph G.;Thatcher, Robert J.;De Ornellas, Sara;Whitwood, Adrian C.;Fairlamb, Ian J. S.. And the article was included in Journal of Organic Chemistry in 2009.Application In Synthesis of (2R,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol hydrate This article mentions the following:
Pd/Cu-mediated direct arylation of 2′-deoxyadenosine with various aryl iodides provides 8-arylated 2′-deoxyadenosine derivatives in good yields. Following significant reaction optimization, it has been determined that a substoichiometric quantity of piperidine (secondary amine) in combination with cesium carbonate is necessary for effective direct arylation. The general synthetic protocol allows lower temperature direct arylations, which minimizes deglycosylation. The origin of the piperidine effect primarily derives from the in situ generation of Pd(OAc)2[(CH2)5NH]2. Various copper(I) salts have been evaluated; only CuI provides good yields of the 8-arylated-2′-deoxyadenosines. Copper(I) appears to have a high binding affinity for 2′-deoxyadenosine, which explains the mandatory requirement for stoichiometric amounts of this key component. The conditions are compared with more general direct arylation protocols, e.g., catalytic Pd, ligand, acid additives, which do not employ copper(I). In each case, no detectable arylation of 2′-deoxyadenosine was noted. The conformational preferences of the 8-aryl-2′-deoxyadenosine products have been determined by detailed spectroscopic (NMR) and single crystal X-ray diffraction studies. Almost exclusively, the preferred solution-state conformation was determined to be syn-C2′-endo (ca. 80%). The presence of a 2-pyridyl group at the 8-position further biases the solution-state equilibrium toward this conformer (ca. 88%), due to an addnl. H-bond between H1′ and the pyridyl nitrogen atom. The Pd/Cu catalyst system has been found to be unique for adenosine type substrates, the reactivity of which has been placed into context with the reported direct arylations of related 1H-imidazoles. The reactivity of other purine nucleosides has been assessed, which has revealed that both 2′-deoxyguanosine and guanosine are incompatible with the Pd/Cu-direct arylation conditions. Both substrates appear to hinder catalysis, akin to the established inhibitory effects in Suzuki cross-couplings with arylboronic acids. In the experiment, the researchers used many compounds, for example, (2R,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol hydrate (cas: 16373-93-6Application In Synthesis of (2R,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol hydrate).
(2R,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol hydrate (cas: 16373-93-6) belongs to tetrahydrofuran derivatives. Tetrahydrofuran (THF), or oxolane, is mainly used as a precursor to polymers. Being polar and having a wide liquid range, THF is a versatile solvent. THF can also be synthesized by catalytic hydrogenation of furan. This allows certain sugars to be converted to THF via acid-catalyzed digestion to furfural and decarbonylation to furan, although this method is not widely practiced. THF is thus derivable from renewable resources.Application In Synthesis of (2R,3S,5R)-5-(6-Amino-9H-purin-9-yl)-2-(hydroxymethyl)tetrahydrofuran-3-ol hydrate
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem