Isomerization of α-Pinene Oxide to Trans-Pinocarveol

Abstract

In addition to being a natural fragrance and EU/WHO-approved food additive, the bicyclic monoterpene trans-pinocarveol (TPC) is a versatile chiral building block for the generation of societally important small molecules. Selective oxidation strategies that leverage α-pinene constitute the most direct and sustainable routes to access this target, where they remain in the vanguard of contemporary approaches to generate molecular complexity from this chiral pool resource. However, the subsequent isomerization of α-pinene oxide (APO) to TPC is complicated by competing 1,2-alkyl shifts leading to inevitable for action of various monocyclic products. Motivated by this challenge, an operationally simple protocol to enable the efficient isomerization of APO to TPC is disclosed that leverages inexpensive pyridinium halides as catalysts. This enabling strategy can be performed on a decagram scale, and catalyst recycling is demonstrated through the deployment of HBr-treated commercial 4-polyvinylpyridine.