Dichotomy in Regioselective Cross-Coupling Reactions of 6,8-Dichloropurines with Phenylboronic Acid and Methylmagnesium Chloride: Synthesis of 6,8-Disubstituted Purines

Michal Hocek; Dana Hocková; Hana Dvořáková

doi:10.1055/s-2004-816012

PAPER

Dichotomy in Regioselective Cross-Coupling Reactions of 6,8-Dichloropurines with Phenylboronic Acid and Methylmagnesium Chloride: Synthesis of 6,8-Disubstituted Purines

Michal Hocek*^a, Dana Hocková^a, Hana Dvořáková^b
^a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic
Fax: +42(220)183559; e-Mail: hocek@uochb.cas.cz;
^b NMR Laboratory, Prague Institute of Chemical Technology, 16628 Prague 6, Czech Republic

Abstract

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Abstract

Pd-catalyzed cross-coupling reaction of 6,8-dichloro-9-(tetrahydropyran-2-yl)purine with one equivalent of phenylboronic acid proceeded regioselectively to give 8-chloro-6-phenylpurine, while the analogous Fe-catalyzed reaction with methylmagnesium chloride gave the 6-chloro-8-methylpurine derivative as major product. Both types of the monochloropurine intermediates were subjected to other cross-coupling reactions or nucleophilic substitutions affording the 9-(tetrahydropyran-2-yl)-6,8-disubstituted purines that were easily deprotected to 8-substituted 6-phenylpurines or 6-substituted 8-methylpurines. Attempted analogous reactions with benzylmagnesium chloride and phenylmagnesium bromide gave low conversions and little selectivity.

Key words

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

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References

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