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 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 butyl trifluoromethanesulfonate ("triflate") inevitably give rise to product mixtures, as the 5-lithio species is more slowly intercepted than it can revert to the alpha-metallomer by a rapid, though intermolecular, dynamic equilibration process. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)