Asymmetric Synthesis of Iridoid Derivatives Using Resolved 2‐Phenylindoline as a Chiral Auxiliary

An asymmetric synthetic route to cis,cis‐nepetalactol (component of the sex pheromone for the hop aphid, Phorodon humuli) is presented. 2‐Phenylindoline was resolved to provide a chiral auxiliary for the cycloaddition of oxocitral. The resolution was made by chromatographic separation of the diastereomers of the urea derivative made from 2‐phenylindoline and with (R)‐(+)‐α‐methylbenzyl isocyanate, followed by reductive cleavage of the isolated diasteromers using diborane. The cycloaddition of oxocitral using (S)‐2‐phenylindoline yielded an enantiopure product after chromatography. Hydrolysis of the cycloaddition adduct yielded gastrolactol (3). As gastrolactol is a versatile synthon for the synthesis of iridoids, the overall procedure provides a general asymmetric route to elaborated iridoids. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)