Methods for selective deuterium-incorporation into drug-like molecules have become extremely valuable due to the commercial and biological importance of deuterated compounds. Selective C2-deuteration of indoles currently requires the installation of directing groups on nitrogen. Herein, we report the directing group free, Pd(OAc)2 catalysed, C2-selective deuteration of indoles with CD3CO2D in high yields and selectivity. Slight modification of the reaction conditions also allows selective access to C3- as well as C2-and-C3-deuterated indoles, providing a user-friendly, programmable deuteration scaffold.
Experimental procedures and characterization data (PDF)