Urea-Catalyzed Vinyl Carbocation Formation Enables Mild Functionalization of Unactivated C–H Bonds
Abstract
Herein we report the 3,5-bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C–H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C–H insertion and Friedel–Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen-bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C–O bonds. Despite the highly Lewis-acidic nature of these catalysts that enables triflate abstraction from sp2 carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis-basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.
Additional Information
© 2020 American Chemical Society. Received 22 May 2020. Published online 19 June 2020. Published in issue 16 October 2020. Financial support for this work was generously provided by the NIH-NIGMS (R35 GM128936), David and Lucile Packard Foundation (to H.M.N.), the Alfred P. Sloan Foundation (to H.M.N.), the Pew Charitable Trusts (to H.M.N), and the National Science Foundation (DGE-1650604 to S.P. and B.W.). A.L.B., S.P., and B.W. acknowledge the Christopher S. Foote Fellowship for funding. A.L.B. thanks UCLA for Dissertation Year Fellowship funding. We thank the UCLA Molecular Instrumentation Center for NMR and mass spectroscopy instrumentation as well as the mass spectrometry facility at the University of California, Irvine. The authors declare no competing financial interest.Attached Files
Submitted - urea-catalyzed-functionalization-of-unactivated-c-h-bonds.pdf
Supplemental Material - ol0c01745_si_001.pdf
Files
| Name | Size | Download all |
|---|---|---|
|
md5:fe5243b458c0ff2b989754926adb60f1
|
1.2 MB | Preview Download |
|
md5:732fdad12901dec48bc7d595b3592861
|
52.3 MB | Preview Download |
Additional details
- Alternative title
- Urea-Catalyzed Functionalization of Unactivated C–H Bonds
- Eprint ID
- 110211
- Resolver ID
- CaltechAUTHORS:20210811-225351355
- R35 GM128936
- NIH
- David and Lucile Packard Foundation
- Alfred P. Sloan Foundation
- Pew Charitable Trust
- DGE-1650604
- NSF Graduate Research Fellowship
- UCLA
- Created
-
2021-08-13Created from EPrint's datestamp field
- Updated
-
2021-08-13Created from EPrint's last_modified field