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Journal of the American Chemical Society
We have demonstrated its superb synthetic viability, both
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efficiency and selectivity, using molecules with varying degrees
of complexity and a number of different functional groups.
Significantly, our current method can be successfully
implemented on the highly chemoselective direct deoxygenation
of alkaloids and regioselective direct monoꢀdeoxygenation of
steroids with multiple secondary hydroxyl groups on both small
and semiꢀgram scales. Striking features of our method also
include relatively mild thermal conditions, as well as innocuous
byꢀproducts. The indispensable role of ruthenium catalyst,
bidentate phosphine ligand dmpe (L ), a catalytic amount of
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Practice; Oxford University Press: 2000.
(10) For details on our early development of iridiumꢀcatalyzed direct
deoxygenation method, see: Huang, J.ꢀL.; Dai, X.ꢀJ.; Li, C.ꢀJ. Eur. J. Org.
Chem. 2013, 6496ꢀ6500.
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DMSO, and a subꢀstoichiometric amount of base imply a
transitionꢀmetalꢀassisted reductive WK transformation. While
further experimental evidence is required to elucidate the
mechanism of this deoxygenation chemistry, our new redoxꢀbased
approach has great potential to become a useful synthetic tool for
Chem. Soc. 1963, 1855ꢀ1858. (c) Furrow, M. E.; Myers, A. G. J. Am.
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Slatford, P. A.; Lowe, J. P.; Mahon, M. F.; Whittlesey, M. K.; Williams, J.
M. J. Dalton Trans. 2009, 716ꢀ722. (b) Bower, J. F.; Kim, I. S.; Patman,
R. L.; Krische, M. J. Angew. Chem. Int. Ed. 2009, 48, 34ꢀ46. (c) Hamid,
M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal. 2007,
3
the direct sp C−O defunctionalization in complex molecules.
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49, 1555ꢀ1575. (d) Dobereiner, G. E.; Crabtree, R. H. Chem Rev 2010,
10, 681ꢀ703.
ASSOCIATED CONTENT
Supporting Information
(13) (a) Zhang, J.; Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.;
Milstein, D. Organometallics 2004, 23, 4026ꢀ4033. (b) Kawahara, R.;
Fujita, K.ꢀi.; Yamaguchi, R. Angew. Chem. Int. Ed. 2012, 51, 12790ꢀ
12794. (c) Baratta, W.; Bossi, G.; Putignano, E.; Rigo, P. Chem. Eur. J.
2011, 17, 3474ꢀ3481.
Experimental details and spectroscopic data for all products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(14) Calligaris, M. Coord. Chem. Rev. 2004, 248, 351ꢀ375.
(15) (a) Hamid, M. H. S. A.; Allen, C. L.; Lamb, G. W.; Maxwell, A. C.;
AUTHOR INFORMATION
Maytum, H. C.; Watson, A. J. A.; Williams, J. M. J. J. Am. Chem. Soc.
2009, 131, 1766ꢀ1774. (b) Gunanathan, C.; Milstein, D. Science 2013,
Corresponding Author
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41, 1229712. (c) Gunanathan, C.; BenꢀDavid, Y.; Milstein, D. Science
007, 317, 790ꢀ792. (d) Kawahara, R.; Fujita, K.ꢀi.; Yamaguchi, R. J. Am.
Chem. Soc. 2012, 134, 3643ꢀ3646.
(16) Junge, H.; Loges, B.; Beller, M. Chem. Commun. 2007, 522ꢀ524.
(17) Enyong, A. B.; Moasser, B. J. Org. Chem. 2014, 79, 7553ꢀ7563.
Notes
The authors declare no competing financial interest.
(18) Birkholz, M.ꢀN.; Freixa, Z.; van Leeuwen, P. W. N. M. Chem. Soc.
Rev. 2009, 38, 1099ꢀ1118.
ACKNOWLEDGMENTS
(19) (a) Szmant, H. H.; Román, M. N. J. Am. Chem. Soc. 1966, 88, 4034ꢀ
4039. (b) Wallace, T. J.; Hofmann, J. E.; Schriesheim, A. J. Am. Chem.
Soc. 1963, 85, 2739ꢀ2743.
The authors acknowledge the Canada Research Chair Foundation
(to C.ꢀJ. Li), the CFI, FQRNT Center for Green Chemistry and
(
20) (a) Nixon, T. D.; Whittlesey, M. K.; Williams, J. M. J. Dalton Trans.
009, 753ꢀ762. (b) Guillena, G.; Ramón, D. J.; Yus, M. Angew. Chem. Int.
Ed. 2007, 46, 2358ꢀ2364.
Catalysis, NSERC, and McGill University for financial support.
Dr. Z.ꢀW. Chen and Dr. F. Wang are greatly appreciated for their
generous helps on preparation of some alcohol substrates. We
acknowledge Dr. J.ꢀL. Huang on his initial discovery of the
deoxygenated product using the iridium catalysis. We thank a
generous sample donation of compound 8 from Professor Claude
Spino at Université de Sherbrooke. X.ꢀJ. Dai thanks the chemistry
department for a doctoral fellowship (Molson & Hilton Hart
fellowship).
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21) Afagh, N. A.; Yudin, A. K. Angew. Chem. Int. Ed. 2010, 49, 262ꢀ310.
22) Wei, L.ꢀL.; Hsung, R. P.; Sklenicka, H. M.; Gerasyuto, A. I. Angew.
Chem. Int. Ed. 2001, 40, 1516ꢀ1518.
(23) Zhang, J.; Li, C.ꢀJ. J. Org. Chem. 2002, 67, 3969ꢀ3971.
(24) Li, C.ꢀJ.; Zhang, J.; Methods for synthesizing heterocycles and
therapeutic use of the heterocycles for cancers. US patent 7250423, July
3
1, 2007.
(25) While methods for the selective deoxygenation of 13 are not
available, monoꢀdeoxygenation of a similar steroid compound has been
reported, see: Denancé, M.; Guyot, M.; Samadi, M. Steroids 2006, 71,
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TOC graphic
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