2‐ and 6‐Purinylmagnesium Halides in Dichloromethane: Scope and New Insights into the Solvent Influence on the C−Mg Bond

The generation of positionally stable purin‐2‐ and 6‐yl magnesium halides is complicated by the often very rapid isomerization to give the 8‐yl Grignards. By conducting the reaction in dichloromethane (DCM), we demonstrated that the anion isomerization can be stopped and these stable purin‐2‐ and 6‐yl Grignards react directly with a broad scope of aldehydes in good yields. Furthermore, purine functionalization with ketones has been achieved for the first time in the presence of LaCl3 ⋅ 2LiCl. Density functional theory calculations offer a possible explanation of the special role played by solvent in this chemistry and show that in DCM the C−Mg bond has a less polar character, whereas in THF it is predominantly ionic and much more basic in nature. Highly functionalized purine systems were obtained using aldehydes and, for the first time, ketones through a recently developed iodo‐Mg exchange methodology that works in DCM. DFT calculations suggested that the observed major stability of the C−Mg bond generated in DCM at higher temperature compared to the one in THF might be derived from a less polar character of the C−Mg bond in such non‐coordinating solvent.