Au(I)-catalysis Enables Regioselective Hydrogen Isotope Labeling of Indoles

The gold(I)-catalyzed hydrogen isotope exchange reaction on indoles and related heterocycles is described, under mild conditions and low catalyst loadings, using CD3OD and D2O as readily available deuterium sources. C3-unsubstituted indoles are labeled at the C3 position with an exquisite regioselectivity, while C3-substituted indoles are labeled at the C2 position. The reaction tolerates a number of chemical functions including amines, alcohols, aldehydes, in addition to the most classical functional groups. This method has been applied to the deuterium label-ing of densely functionalized bioactive compounds and to the synthesis of a tritiated analogue of pindolol using tritiated water as isotopic source. Mechanistic study revealed the involvement of aurated indole as key intermediates.