Site-selective direct arylation of unprotected adenine nucleosides mediated by palladium and copper: insights into the reaction mechanism

TY - JOUR

T1 - Site-selective direct arylation of unprotected adenine nucleosides mediated by palladium and copper

T2 - insights into the reaction mechanism

AU - Storr, Thomas E.

AU - Firth, Andrew G.

AU - Wilson, Karen

AU - Darley, Kate

AU - Baumann, Christoph G.

AU - Fairlamb, Ian J. S.

PY - 2008/6/23

Y1 - 2008/6/23

N2 - Reaction conditions facilitating the site-selective direct aryl functionalisation at the C-8 position of adenine nucleosides have been identified. Many different aromatic components may be effectively cross-coupled to provide a diverse array of arylated adenine nucleoside products without the need for ribose or adenine protecting groups. The optimal palladium catalyst loading lies between 0.5 and 5 mol%. Addition of excess mercury to the reaction had a negligible affect on catalysis, suggesting the involvement of a homogeneous catalytic species. A study by transmission electron microscopy (TEM) shows that metal containing nanoparticles, ca. 3 nm with good uniformity, are formed during the latter stages of the reaction. Stabilised PVP palladium colloids (PVP=N-polyvinylpyrrolidone) are catalytically active in the direct arylation process, releasing homogenous palladium into solution. The effect of various substituted 2-pyridine ligand additives has been investigated. A mechanism for the site-selective arylation of adenosine is proposed. (C) 2008 Elsevier Ltd. All rights reserved.

AB - Reaction conditions facilitating the site-selective direct aryl functionalisation at the C-8 position of adenine nucleosides have been identified. Many different aromatic components may be effectively cross-coupled to provide a diverse array of arylated adenine nucleoside products without the need for ribose or adenine protecting groups. The optimal palladium catalyst loading lies between 0.5 and 5 mol%. Addition of excess mercury to the reaction had a negligible affect on catalysis, suggesting the involvement of a homogeneous catalytic species. A study by transmission electron microscopy (TEM) shows that metal containing nanoparticles, ca. 3 nm with good uniformity, are formed during the latter stages of the reaction. Stabilised PVP palladium colloids (PVP=N-polyvinylpyrrolidone) are catalytically active in the direct arylation process, releasing homogenous palladium into solution. The effect of various substituted 2-pyridine ligand additives has been investigated. A mechanism for the site-selective arylation of adenosine is proposed. (C) 2008 Elsevier Ltd. All rights reserved.

KW - direct arylation

KW - purines

KW - C-C bond formation

KW - palladium

KW - copper(I) salts

KW - CROSS-COUPLING REACTIONS

KW - CATALYZED DIRECT ARYLATION

KW - H BOND FUNCTIONALIZATION

KW - INCLUDING FREE (NH)-IMIDAZOLE

KW - DIRECT C-2 ARYLATION

KW - GENERATED IN-SITU

KW - HETEROGENEOUS CATALYSIS

KW - ARYL HALIDES

KW - LIGANDLESS CONDITIONS

KW - HALOGENATED NITROGEN

UR - http://www.scopus.com/inward/record.url?scp=44149100021&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2008.01.062

DO - 10.1016/j.tet.2008.01.062

M3 - Article

SN - 0040-4020

VL - 64

SP - 6125

EP - 6137

JO - Tetrahedron

JF - Tetrahedron

IS - 26

ER -