Organic Letters
Letter
Scheme 5. Proposed Mechanism for the Regiodivergent
RhAAC
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Detailed experimental procedures and characterization
of new compounds (1H NMR, 13C NMR, HRMS)
AUTHOR INFORMATION
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Corresponding Author
ORCID
Author Contributions
§N.Z. and M.L. contributed equally.
Notes
The authors declare no competing financial interest.
addition. Internal thioalkyne 1 is oxidized to internal sulfonyl
alkyne 1′. Intermediate A could be generated by the initial
combination of π-acidic Rh(I) with 1′ and azide 2. The high
1,4-regioselectivity is derived from intermediate A. The
electron-withdrawing sulfonyl group reverses the initial
reactivity of the thioalkyne and could not coordinate with
Rh(I). Then, Rh-carbene intermediate B is formed through the
oxidative addition of the β-carbon of the alkyne and azide.
After the subsequent Rh-assisted isomerization of intermediate
B to intermediate C followed by the reductive elimination of
intermediate C, desired fully substituted 4-sulfonyl-1,2,3-
triazole 3 is formed with high 1,4-regioselectivity. For the
sulfide-controlled RhAAC reaction to access fully substituted
5-sulfonyl-1,2,3-triazoles, the cycloaddition occurs first accom-
panied by the in situ oxidation. According to Sun and Jia’s
study in the IrAAC reaction,12 we propose that the
intermediate A′ could be formed through internal thioalkyne
1 and azide 2 coordinating to the π-acidic Rh(I). Oxidative
cyclization yields metallacycle B′, in which the sulfide strongly
coordinates to the Rh, stabilizing the system and providing the
high 1,5-regioselectivity. None of the other groups on the
internal thioalkyne can coordinate to the rhodium. Then, 4′ is
generated from intermediate C′ by the reductive elimination of
B′. Desired fully substituted 5-sulfonyl-1,2,3-triazole 4 could
be acquired from 4′ by the in situ oxidation in one pot way
with excellent 1,5-regioselectivity.
In summary, we have developed the regiodivergent synthesis
of both fully substituted 4-sulfonyl-1,2,3-triazoles and 5-
sulfonyl-1,2,3-triazoles in high regioselectivities and yields
under mild conditions in one step and in one pot, respectively.
The rhodium(I)-catalyzed azide−alkyne cycloaddition
(RhAAC) reactions could be well controlled by sulfur(II) or
sulfur(VI) to respectively give excellent 1,4- or 1,5-
regioselectivities. The potential utility of this approach was
validated by the gram-scale reactions, the application to
carbohydrates, and the tandem CuAAC-RhAAC reaction.
Further mechanistic studies and advanced theoretical calcu-
lations for the transition states and intermediates are underway
in our laboratory.
ACKNOWLEDGMENTS
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This work was supported by grants from the Doctoral Program
Foundation of Liaoning Province (Nos. 20170520378 and
20170520274), the Fundamental Research Funds for the
Central Universities (Nos. DUT16RC(3)114 and
DUT18LK25) and the National Natural Science Foundation
of China (Nos. 21702025 and 51703018). We thank Prof.
Weiping Tang (University of Wisconsin-Madison) for
insightful discussions.
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