Carbohydrate-Derived Bis(oxazoline) Ligand in the Total Synthesis of Grenadamide

Abstract

Using an optimised carbohydrate-based bis(oxazoline) ligand and copper(I) triflate, unactivated aliphatic alkenes were cyclopropanated­ with simple ethyl diazoacetate, giving the corresponding products in good yields and high stereoselectivities. The trans-disubstituted cyclopropyl carboxylic acid ester derived from 1-nonene was subsequently used as the key intermediate for the synthesis of the (+)-enantiomer of the natural product (-)-grenadamide. The efficient and high-yielding approach towards grenadamide reported here is the first to utilise asymmetric cyclopropanation for the construction of the chiral cyclopropyl unit.