Nickel-catalysed asymmetric heteroarylative cyclotelomerization of isoprene

Monoterpenoids are a class of isoprenoids produced from geranyl diphosphate by various monoterpene synthases. Nature has evolved over millions of years to produce various cyclic monoterpenoids. Herein, we present a serendipitous creation of an unnatural monoterpene skeleton through heteroarylative telomerization of isoprene with heterocycles. Under nickel catalysis, a series of cyclic monoterpene derivatives bearing quaternary carbon stereocentre are constructed with up to 98% yield and 97% enantiomeric excess. Preliminary mechanistic studies suggest this atom-economic reaction proceeds through an enantioselective dimerization of isoprene and a sequential C-H alkylation of heterocycles pathway. This work not only contributes an efficient enantioselective transformation of bulk chemical isoprene, but also provides a guide to create an unnatural monoterpene framework that may exhibit different biological activities.

Automated summary

The atom-economic reaction of heteroarylative telomerization of isoprene with heterocycles provides an efficient enantioselective transformation method for creating an unnatural monoterpene framework, which may exhibit different biological activities.