Editing Kinetic isotope effect (section)

==== DEPT-55 NMR ====
Though KIE measurements at natural abundance are a powerful tool for understanding reaction mechanisms, the amounts of material needed for analysis can make this technique inaccessible for reactions that use expensive reagents or unstable starting materials. To mitigate these limitations, Jacobsen and coworkers developed {{sup|1}}H to {{sup|13}}C polarization transfer as a means to reduce the time and material required for KIE measurements at natural abundance. The [[distortionless enhancement by polarization transfer]] (DEPT) takes advantage of the larger [[gyromagnetic ratio]] of {{sup|1}}H over {{sup|13}}C, 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.<ref>{{cite journal | vauthors = Kwan EE, Park Y, Besser HA, Anderson TL, Jacobsen EN | title = 13C Kinetic Isotope Effect Measurements Enabled by Polarization Transfer | journal = Journal of the American Chemical Society | volume = 139 | issue = 1 | pages = 43–46 | date = January 2017 | pmid = 28005341 | doi = 10.1021/jacs.6b10621 | pmc = 5674980 }}</ref>

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.<ref>{{cite journal | vauthors = Park Y, Harper KC, Kuhl N, Kwan EE, Liu RY, Jacobsen EN | title = Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions | journal = Science | volume = 355 | issue = 6321 | pages = 162–166 | date = January 2017 | pmid = 28082586 | pmc = 5671764 | doi = 10.1126/science.aal1875 | bibcode = 2017Sci...355..162P }}</ref> Glycosylation is a special case of nucleophilic substitution that lacks clear definition between S{{sub|N}}1 and S{{sub|N}}2 mechanistic character. The presence of the oxygen adjacent to the site of displacement (i.e., C1) can stabilize positive charge. This charge stabilization can cause any potential concerted pathway to become asynchronous and approaches intermediates with oxocarbenium character of the S{{sub|N}}1 mechanism for glycosylation.

[[File:Reaction Scheme for Thiourea catalyzed glycosylation of galactose.png|alt=Reaction scheme for thiourea catalyzed glycosylation of galactose|none|thumb|492x492px|Reaction scheme for thiourea catalyzed glycosylation of galactose]]
[[File:Kinetic Isotope Effect Measurements for Thiourea catalyzed glycosylation of galactose.png|alt=13C kinetic isotope effect measurements for thiourea catalyzed glycosylation of galactose|none|thumb|350x350px|{{sup|13}}C kinetic isotope effect measurements for thiourea catalyzed glycosylation of galactose]]

Jacobsen and coworkers observed small normal KIEs at C1, C2, and C5 which suggests significant oxocarbenium character in the transition state and an asynchronous reaction mechanism with a large degree of charge separation.