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the urea product of celestolide when a chiral manganese
1
2
3
4
5
6
7
8
salen catalyst was employed, representing the first example
of an enantioselective synthesis of an organic urea via di-
rect C-H activation. Our mechanistic and EPR studies di-
rectly implicate the involvement of a MnIV-bound rebound
intermediate in our reaction. Therefore, we postulate the
intermediacy of a reactive trans-diisocyanato-manga-
nese(IV) complex in C-H isocyanation. We then success-
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demonstrated its capacity for isocyanate transfer to alkyl
radicals. These results contribute to our mechanistic un-
derstanding of heteroatom-rebound catalysis and fully
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ASSOCIATED CONTENT
Detailed experimental procedures, crystal structure data, spectro-
scopic data for all new compounds, and details for DFT calculation.
This material is available free of charge via the Internet at
AUTHOR INFORMATION
(18) (a) Carnaroglio, D.; Martina, K.; Palmisano, G.; Penoni, A.;
Domini, C.; Cravotto, G. Beilstein J. Org. Chem. 2013, 9, 2378. (b)
Thalluri, K.; Manne, S. R.; Dev, D.; Mandal, B. J. Org. Chem. 2014,
79, 3765. (c) Spyropoulos, C.; Kokotos, C. G. J. Org. Chem. 2014, 79,
4477.
Corresponding Author
Author Contributions
†These authors contributed equally.
Notes
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B. R.; Cases, S.; Cheng, Y.; Do, Z. N.; Mehra, U.; Tran, V.; Vincelette,
J.; Waszczuk, J.; White, K.; Wong, K. R.; Zhang, L.-N.; Jones, P. D.;
Hammock, B. D.; Patel, D. V.; Whitcomb, R.; MacIntyre, D. E.; Sabry,
J.; Gless, R. Bioorg. Med. Chem. Lett. 2011, 21, 983. (b) Chen, D.;
Whitcomb, R.; MacIntyre, E.; Tran, V.; Do, Z. N.; Sabry, J.; Patel, D.
V.; Anandan, S. K.; Gless, R.; Webb, H. K. J. Clin. Pharmacol. 2012,
52, 319. (c) Jones, P. D.; Tsai, H.-J.; Do, Z. N.; Morisseau, C.;
Hammock, B. D. Bioorg. Med. Chem. Lett. 2006, 16, 5212.
(20) (a) Moriguchi, S.; Kimura, Y.; Yokoo, H.; Furutoku, I.; Ebisawa,
H. Japanese Patent JPS6023313(A), Feb. 2, 1985. (b) Gomtsyan, A.;
Bayburt, E. K.; Koenig, J. R.; Lee, C.-H. U.S. Patent 2004/0254188A1,
Dec 16, 2004. .
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This research was supported by the US National Science Founda-
tion award CHE-1464578. XH thanks the Howard Hughes Medical
Institute for fellowship support. The authors thank Prof. A. G.
Doyle for access to chiral HPLC and Dr. Phil Jeffrey for assistance
in crystal data collection.
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