Organometallic reaction mechanism elucidation examples Colletto et al. developed a regioselective -arylation of benzo[b]thiophenes at room temperature with aryl iodides as coupling partners and sought to understand the mechanism of this reaction by performing natural abundance kinetic isotope effect measurements via single pulse NMR. The observation of a primary 13C isotope effect at C3, an inverse 2H isotope effect, a secondary 13C isotope effect at C2, and the lack of an 2H isotope effect at C2 lead Colletto et al. to suggest a Heck-type reaction mechanism for the regioselective -arylation of benzo[b]thiophenes at room temperature with aryl iodides as coupling partners. Frost et al. sought to understand the effects of Lewis acid additives on the mechanism of enantioselective palladium catalyzed C-N bond activation using natural abundance kinetic isotope effect measurements via single pulse NMR. The primary 13C kinetic isotope effect observed in the absence of BPh3 suggests a reaction mechanism with rate limiting cis oxidation into the C–CN bond of the cyanoformamide. The addition of BPh3 causes a relative decrease in the observed 13C kinetic isotope effect which led Frost et al. to suggest a change in the rate limiting step from cis oxidation to coordination of palladium to the cyanoformamide. DEPT-55 NMR Although kinetic isotope effect measurements at natural abundance are a powerful tool for understanding reaction mechanisms, the amounts of material required for analysis can make this technique inaccessible for reactions that employ expensive reagents or unstable starting materials. In order to mitigate these limitations, Jacobsen and coworkers developed 1H to 13C polarization transfer as a means to reduce the time and material required for kinetic isotope effect measurements at natural abundance. The distortionless enhancement by polarization transfer (DEPT) takes advantage of the larger gyromagnetic ratio of 1H over 13C to theoretically improve measurement sensitivity by a factor of 4 or decrease experiment time by a factor of 16. This method for natural abundance kinetic isotope measurement is favorable for analysis for reactions containing unstable starting materials, and catalysts or products that are relatively costly. Jacobsen and coworkers identified the thiourea-catalyzed glycosylation of galactose as a reaction that met both of the aforementioned criteria (expensive materials and unstable substrates) and was a reaction with a poorly understood mechanism. Glycosylation is a special case of nucleophilic substitution that lacks clear definition between SN1 and SN2 mechanistic character. The presence of the oxygen adjacent to the site of displacement (i.e.,