Journal of the American Chemical Society
this reaction engine advances MH HAT chemistry beyond
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classical radical traps and may allow a much greater
breadth of coupling partners, as exemplified by iodoarenes
and iodoalkanes. We aim to adapt this chemistry to a range
433 (d) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle, A.
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2016, 138, 5016.
of crossꢀcoupling reactions that are capable of forging chalꢀ
31
lenging bonds between complex subunits,
which may
help small molecule therapeutics ‘escape from flatland.’32
ASSOCIATED CONTENT
Supporting Information. The Supporting Information is
available free of charge on the ACS Publications website.
Detailed experimental procedures and spectral data. This
material is available free of charge via the Internet at
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(9) For example: (a) Iwai, Y.; Gligorich, K. M.; Sigman, M. S. Angew.
Chem. Int. Ed. 2008, 47, 3219; (b) Friis, S. D.; Pirnot, M. T.; Buchꢀ
wald, S. L. J. Am. Chem. Soc. 2016, 138, 8372; (c) Nakao, Y.;
Kashihara, N.; Kanyiva, K. S.; Hiyama, T. Angew. Chem. Int. Ed.
2010, 49, 4451; (d) Gao, K.; Yoshikai, N. J. Am. Chem. Soc. 2011,
133, 400; (e) Mukai, T.; Hirano, K.; Satoh, T.; Miura, M. J. Org.
Chem. 2009, 74, 6410; (f) Andou, T.; Saga, Y.; Komai, H.; Matsuꢀ
naga, S.; Kanai, M. Angew. Chem. Int. Ed. 2013, 52, 3213; (g) Semꢀ
ba, K.; Ariyama, K.; Zheng, H.; Kameyama, R.; Sakaki, S.; Nakao,
Y. Angew. Chem. Int. Ed. 2016, 55, 6275.
AUTHOR INFORMATION
Corresponding Author
Author Contributions
(10) Black, D. A.; Fagnou, K., Science of Synthesis, 2010, 45, 627. See
section 45.14.1.1.2.
‡These authors contributed equally.
(11) (a) Crisenza, G. E. M.; McCreanor, N. G.; Bower, J. F. J. Am. Chem.
Soc. 2014, 136, 10258; (b) Crisenza, G. E. M.; Sokolova, O. O.;
Bower, J. F. Angew. Chem. Int. Ed. 2015, 54, 14866; (c) Scheme 2 in
Pan, S.; Ryu, N.; Shibata, T. J. Am. Chem. Soc. 2012, 134, 17474.
Enol ethers are similarly biased: (d) Ebe, Y.; Nishimura, T. J. Am.
Chem. Soc. 2015, 137, 5899; (e) Hatano, M.; Ebe, Y.; Nishimura, T.;
Yorimitsu, H. J. Am. Chem. Soc. 2016, 138, 4010.
(12) As Bower notes, sec- and tertꢀalkyl groups can be appended to
arenes using alkyl electrophiles or nucleophiles instead of alkenes.
For examples, see: (a) Dreher, S. D.; Dormer, P. G.; Sandrock, D. L.;
Molander, G. A. J. Am. Chem. Soc. 2008, 130, 9257 and references
therein. Also, Heck arylation can select for the internal position. For
example: (b) Qin, L.; Ren, X.; Lu, Y.; Li, Y.; Zhou, J. Angew. Chem.
Int. Ed. 2012, 51, 5915.
ACKNOWLEDGMENT
Financial support for this work was provided by the NSF
GRFP (S. A. G and J. M.ꢀM.) and the JSPS (A. Y.) Addiꢀ
tional support was provided by Eli Lilly, Novartis, Bristolꢀ
Myers Squibb, Amgen, BoehringerꢀIngelheim, the Sloan
Foundation and the Baxter Foundation. We thank Ruben M.
Martinez for large scale preparation of PhSi(OiꢀPr)H2 (Ruꢀ
benSilane) and Professor Keary Engle for helpful discusꢀ
sions.
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