Metalated 1-(p-methoxybenzyl)pyrazole: a structural chameleon

When treated with either butyllithium or lithium diisopropylamide, 1-(p-methoxybenzyl)pyrazole undergoes metalation at the exocyclic alpha-position but mutates to the 5-lithio species in the course of a few minutes or hours. Trapping the intermediates with a rapidly reacting electrophile such as chlorotrimethysilane or carbon dioxide offers selective access to either of the two possible regioisomers. On the other hand, the relatively inert 1-iodobutane and Bu triflate inevitably give rise to product mixts., as the 5-lithio species is more slowly intercepted than it can revert to the alpha-metalomer by a rapid, though intermol., dynamic equilibration process. [on SciFinder (R)]