Organic Letters
Letter
Scheme 3. Proposed Reaction Mechanisms of the JU-3CR
isocyanide reacts with the iminium ion on the opposite face of
the bulky siloxy group, resulting in an SN1-type transition state
(TS2). Here, the positive charge of the iminium ion is not
stabilized by the carboxylate ion, resulting in the formation of
the trans isomer (path 2). On the basis of the balance of these
two mechanisms, the diastereoselectivity is affected by the
electronic properties of the isocyanides. Therefore, electron-
rich isocyanides prefer the more positively charged transition
state (TS2), and electron-deficient isocyanides prefer the more
neutral transition state (TS1).
Natural Products” (Grant 24102502 to S.I.), The Ministry of
Education, Culture, Sports, Science and Technology through
the Program for Leading Graduate Schools (Hokkaido
University “Ambitious Leader’s Program”), and the Platform
Project for Supporting Drug Discovery and Life Science
Research (Platform for Drug Discovery, Informatics and
Structural Life Science).
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́
In conclusion, we have developed a diastereodivergent JU-
3CR in which the stereochemical outcome can be controlled by
the choice of solvent, with cis and trans isomers being obtained
in toluene and HFIP, respectively. We have also revealed
differences in the reaction mechanisms in the two solvents. In
toluene, the reaction proceeds through an SN2-type mechanism
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as previously suggested by Flanagan and Joullie.2
́
However, the
trans isomer is generated selectively via an SN1-type mechanism
in HFIP. The presence of these two mechanisms in the JU-3CR
is important for the development of the first asymmetric JU-
3CR and Ugi four-component reaction.
ASSOCIATED CONTENT
* Supporting Information
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(10) Schedler, D. J. A.; Godfrey, A. G.; Ganem, B. Tetrahedron Lett.
1993, 34, 5035.
S
The Supporting Information is available free of charge on the
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Complete experimental procedures and characterization
data for all new compounds (PDF)
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AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We appreciate the reviewer who pointed out to us the
pioneering study by Flanagan and Joullie
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(ref 2). We thank Ms.
S. Oka and Ms. A. Tokumitsu (Center for Instrumental
Analysis, Hokkaido University) for measurement of the mass
spectra. This research was supported by a JSPS Grants-in-Aid
for Scientific Research (B) (Grant 25293026 to S.I.) and
Scientific Research on Innovative Areas “Chemical Biology of
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