Cyclization and rearrangement products from coupling reactions between terminal o-alkynylphenols or o-ethynyl(hydroxymethyl)benzene and 6-halopurines

Cyclization reactions on 6-[(2-hydroxyphenyl)ethynyl]purines, 6-[(2-hydroxymethylphenyl)ethynyl]purines and 6-[(2-hydroxyphenyl)propyn-1-yl]purines have been studied. 6-(2-Benzofuryl)purines are readily available via a one-pot Sonogashira coupling-cyclization between 6-iodopurine and 2-ethynylphenol. When the same reaction was performed with o-(hydroxymethyl)ethynylbenzene, 6-[isobenzofuran-1(3H)-ylidenemethyl]purine was formed, mainly as the (E)-isomer. Acid catalyzed isomerization of the (E)-compound afforded the (Z)-isomer. The latter compound was also formed from a two-step reaction; Sonogashira coupling with O-silylated alkyne followed by deprotection and subsequent 5-exo cyclization. Sonogashira coupling between 6-halopurines and 2-propynylphenol gave only the alkyne coupling product and no cyclization took place. However, the Sonogashira product was unexpectedly rearranged to 6-(3-phenoxypropa-1,2-dienyl)purines under basic conditions. Theoretical calculations demonstrated that the allenes are more stable than their alkyne isomers.