Regioselectivity in Cross-Coupling Reactions of 2,6,8-Trichloro-9-(tetrahydropyran-2-yl)purine: Synthesis of 2,6,8-Trisubstituted Purine Bases

Michal Hocek; Radek Pohl

doi:10.1055/s-2004-834881

PAPER

Regioselectivity in Cross-Coupling Reactions of 2,6,8-Trichloro-9-(tetrahydropyran-2-yl)purine: Synthesis of 2,6,8-Trisubstituted Purine Bases

Michal Hocek*, Radek Pohl
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic
Fax: +420(2)20183559; e-Mail: hocek@uochb.cas.cz;

Abstract

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Abstract

The regioselectivity of cross-coupling reactions (Pd-catalyzed Suzuki-Miyaura reactions with phenylboronic acid and Fe-catalyzed reactions with methylmagnesium chloride) of 2,6,8-trichloro-9-(tetrahydropyran-2-yl)purine with varying amounts of the organometallic reagent was studied. In general, the regioselectivity of these reactions was quite low giving mixtures of isomers of mono-, di- and trisubstituted products. Nevertheless, 2,6-dichloro-8-methyl-9-THP-purine (1aab), 2-chloro-6,8-dimethyl-9-THP-purine (1abb) and 2,8-dichloro-6-phenyl-9-THP-purine (1aca) were isolated in acceptable yields and used as intermediates for further cross-coupling reactions giving a series of 2,6,8-trisubstituted 9-THP-purines that were deprotected to the corresponding purine bases. Characteristic ¹³C NMR shifts of CH₃ or ipso-Ph carbons in different positions of the purine ring have been observed enabling rapid and facile identification of the particular isomer.

Key words

purines - nucleobases - cross-coupling reactions - iron - palladium

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