Design of Experiments for Diverse Carbon Isotope Labeling with Aryl Thianthrenium Salts.

A method for accessing structurally diverse carbon-isotope-labeled products from aryl thianthrenium salts has been established. The use of near-stoichiometric amounts of ex situ-generated carbon monoxide along with simple, air-stable palladium catalysts allows for the synthesis and isotope labeling of a broad range of carbonylation products. Design of Experiments enabled rapid optimization and gain of key mechanistic insight. The reaction tolerates electronically diverse electrophiles and could be used for the synthesis and late-stage isotope labeling of several pharmaceutical molecules.