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Synthesis 2004(17): 2869-2876
DOI: 10.1055/s-2004-834881
DOI: 10.1055/s-2004-834881
PAPER
© Georg Thieme Verlag Stuttgart · New YorkRegioselectivity in Cross-Coupling Reactions of 2,6,8-Trichloro-9-(tetrahydropyran-2-yl)purine: Synthesis of 2,6,8-Trisubstituted Purine Bases
Further Information
Received
12 July 2004
Publication Date:
15 October 2004 (online)
Publication History
Publication Date:
15 October 2004 (online)
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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