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Figure 2.PBE0ꢀD3(BJ)/6ꢀ31G*/PCM transition structureforthe
glycosylationof galactose with benzyl alcohol, with laꢀ
belleddistances in Å.19
In conclusion, polarization transfer offers a highly sensitivemethꢀ
od for determiningthe KIEs of protonated carbons at natural
abundance, reducing the amount of sample required by a factor of
three or acquisition time by a factor of nine.In complex or catalytꢀ
ic systems, this method is particularly advantageous: the KIEs of
interest usually belong to protonated carbons, time and material
are at a premium, and high concentrations can be impractical due
to material limitations.The DEPTꢀ55 method was applied successꢀ
fully to analyses of a Diels–Alder reaction and a catalytic glycoꢀ
sylation, with experimental natural abundance KIEs serving both
to validate and differentiateDFT calculations.1aWe hope that our
method will enable the further application of KIE analyses as a
general mechanistic tool, thereby offering new insights into the
mechanisms of organic reactions.
ASSOCIATED CONTENT
Supporting Information
12. Beno, B.R.; Houk, K.N.; Singleton, D.A.J. Am. Chem. Soc.1996,
118, 9984–9985.
13. Hirschi, J.S.; Takeya, T.; Hang C.; Singleton, D.A.J. Am. Chem.
Soc.2009,131, 2397–2403.
Experimental procedures, spectroscopic data, NMR data, and
computational structures.This material is available free of charge
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17.Park, Y.; Harper, K. C; Kuhl, N.; Kwan, E. E.; Liu, R. Y.; Jacobsen,
E. N., Science, accepted for publication.
18.There is no saddle point for bond heterolysis on the potential energy
surface, so evaluation of the EIE represents the best approach to estimatꢀ
ing the KIE for the SN1 pathway. See reference 9.
19. The experimental KIEs are closest to the values predicted by PBE0ꢀ
D3BJ and B3LYP. Given that a dispersionꢀcorrected model should be
physically more reasonable, and that the uncorrected transition structure
features an unusual nonꢀplanar chlorideꢀbinding geometry, the PBE0ꢀ
D3(BJ structure is the model that best fits the observed data.
AUTHOR INFORMATION
Corresponding Author
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
Financial support from the NIH (UO1GM116249 and
RO1GM43214), the NSF (predoctoral fellowship for Y.P.), and
the ACS (SURF award for H.A.B.) are acknowledged. We thank
Dr. Shaw Huang and Mr. William Collins for NMR assistance.
We thank Professor William F. Reynolds for helpful discussions.
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