Capacidad Transacciones recibidas por Internet por accesos a portal del paciente:

In summary, a mild, room temperature method for the introduction of a diverse palette of alkyl groups has been developed. Under a set of unified reaction conditions, primary, secondary, and tertiary alkyltrifluoroborates can be employed in photoredox Minisci chemistry for the first time. This chemistry makes use of an inexpensive, mild oxidant, organic photocatalyst, and requires only one equivalent of alkyl radical partner, providing one of the most cost efficient and sustainable approaches to date. Additionally, enhanced regioselectivity was observed compared to current “state of the art” Minisci-type alkylations. Both of these phenomena may be related to the synchronized, catalytic generation of radicals in conjunction with the in situ generation of BF3 during the course of the reaction. The resultant method has been demonstrated broadly with respect to the heteroarene and alkyltrifluoroborate partners. Furthermore, access to bipyridine-type ligands as well as the late stage diversification of medicinally relevant substructures has been showcased. Finally, NMR studies provided support for a unique, highly activated species caused by the formation of BF3 upon the single-electron oxidation of alkyltrifluoroborates.

Given the wide array of commercially available alkyltrifluoroborates, those synthesized by our laboratory and emerging from other groups, this approach provides a valuable contribution to the Minisci-type alkylation literature and is both highly competitive and complementary to existing protocols. As alkyltrifluoroborates are well behaved, bench stable salts, these reagents will continue to serve as useful “radicals in a bottle” for synthetic chemists.

2.5 References

1 _{Welsch, M. E.; Synder, S. A.; Stockwell, B. R. Curr. Opin. Chem. Biol.2010, 14, 347.} 2 _{McGrath, N. A.; Brichacek, M.; Njardarson, J. T. J. Chem. Educ.2010, 87, 1348.} 3 _{Ducton, M. A. Med. Chem. Commun.2011, 2, 1135.}

4 _{Bunnett, J. F.; Zahler, R. E. Chem. Rev.1951, 49, 273.} 5 _{Joshi, G.; Adimurthy, S. Ind. Eng. Chem. Res.2011, 50,}

6 _{Rodriguez, R. A.; Pan, C. -M.; Yabe, Y.; Kawamata, Y.; Eastgate, M. D.; Baran, P. S. J. Am.}

Chem. Soc.2014, 136, 6908.

7 _{Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew. Chem. Int. Ed.2006, 45, 3484.} 8 _{Ge, S.; Hartwig, J. F. Angew. Chem. Int. Ed.2012, 51, 12837.}

9 _{Minisci, F. Acc. Chem. Res.1975, 8, 165.}

10 _{Minisci, F.; Bernardi, R.; Bertini, F.; Galli, R.; Perchinunmmo, M. Tetrahedron1971, 27,} 3575.

11 _{Seiple, I. B.; Su, S.; Rodriguez, R. A.; Gianatassio, R.; Fujiwara, Y.; Sobel, A. L.; Baran, P. S.} J. Am. Chem. Soc.2010, 132, 13194.

12 _{Foo, K.; Sella, E.; Thome, I.; Eastgate, M. D.; Baran, P. S. J. Am. Chem. Soc.2014, 136, 5379.} 13 _{Molander, G. A.; Colombel, V.; Braz, V. A. Org. Lett.2011, 13, 1852.}

14 _{Gianatassio, R.; Kawamura, S.; Eprile, C. L.; Foo, K.; Ge, J.; Burns, A. C.; Collins, M. R.;} Baran, P. S. Angew. Chem. Int. Ed.2014, 53, 9851.

15 _{Liu, Y. –Q.; Dai, W.; Wang, C. –Y.; Morris-Natschke, S. L.; Zhou, X. –W.; Yang, L.; Yang, X.}

–M.; Li, W. –Q.; Lee, K. –H. Bioorg. Med. Chem.2012, 22, 7659.

16 _{Goddard, J. -P.; Ollivier, C.; Fensterbank, L. Acc. Chem. Res.2016, 49, 1565.}

17 _{(a) Jin, J.; MacMillan, D. W. C. Nature2015, 525, 87. (b) Nagib, D. A.; MacMillan, D. W. C.} Nature2011, 480, 224. (c) Jin, J.; MacMillan, D. W. C. Angew. Chem. Int. Ed.2015, 54, 1565. 18 _{DiRocco, D. A.; Dykstra, K.; Krska, S.; Vachal, P.; Conway, D. V.; Tudge, M. Angew. Chem.}

Int. Ed.2014, 53, 4802.

19 _{Li, G. -X.; Morales-Rivera, C. A.; Wang, Y.; Gao, F.; He, G.; Liu, P.; Chen, G. Chem. Sci.}

2016, 7, 6407.

21 _{(a) Tellis, J. C.; Primer, D. N.; Molander, G. A. Science2014, 345, 433. (b) Primer, D. N.;}

Karakaya, I.; Tellis, J. C.; Molander, G. A. J. Am. Chem. Soc.2015, 137, 2195. (c) Karakaya, I.; Primer, D. N.; Molander, G. A. Org. Lett.2015, 17, 3294. (d) Yamashita, Y.; Tellis, J. C.; Molander, G. A. Proc. Natl. Acad. Sci. U.S.A.2015, 112, 12026. (e) El Khatib, M.; Serafim, R. A.; Molander, G. A. Angew. Chem. Int. Ed.2016, 55, 254. (f) Ryu, D.; Primer, D. N.; Tellis, J. C.; Molander, G. A. Chem. Eur. J.2016, 22, 120. (g) Amani, J.; Sodagar, E.; Molander, G. A. Org. Lett.2016, 18, 732. (h) Karimi-Nami, R.; Tellis, J. C.; Molander, G. A. Org. Lett.2016, 18, 2572. (i) Tellis, J. C.; Amani, J.; Molander, G. A. Org. Lett.2016, 18, 2572. (j) Yasu, Y.; Koike, T.; Akita, M. Adv. Synth. Catal.2012, 354, 3414.

22 _{Fukuzumi, S.; Kotani, H.; Ohkubo, K.; Ogo, S.; Tkachenko, N. V.; Lemmetyinen, H. J. Am.} Chem. Soc.2004, 126, 1600.

23 _{Huie, R. E.; Clifton, C. L.; Neta, P. Radiat. Physc. Chem.1991, 38, 477.}

24 _{(a) Hamilton, D. S.; Nicewicz, D. A. J. Am. Chem. Soc.2012, 134, 18577. (b) Morse, P. D.;} Nicewicz, D. A. Chem. Sci.2015, 6, 270. (c) Nicewicz, D. A.; Nguyen, T. M. ACS Catal.2014, 4, 355. (d) Grandjean, J.; Nicewicz, D. A. Angew. Chem. Int. Ed.2013, 52, 3967. (e) Riener, M. Nicewicz, D. A. Chem. Sci.2013, 4, 2625. (f) Wilger, D. J.; Gesmundo, N. J.; Nicewicz, D. A. Chem. Sci.2013, 4, 3160. (g) Nguyen, T. M.; Nicewicz, D. A. J. Am. Chem. Soc.2013, 135, 9588. (h) Perkowski, A. J.; Nicewicz, D. A. J. Am. Chem. Soc.2013, 135, 10334. (i) Nicewicz, D. A.; Hamilton, D. S. Synthesis2014, 25, 1191. (j) Nguyen, T. M.; Manohar, N.; Nicewicz, D. A. Angew. Chem. Int. Ed.2014, 53, 6198. (k) Romero, N.; Nicewicz, D. A. J. Am. Chem. Soc.

2014, 136, 17024. (k) Zeller, M. A.; Riener, M.; Nicewicz, D. A. Org. Lett.2014, 16, 4810. (l) Gesmundo, N. J.; Grandjean, J. -M. M.; Nicewicz, D. A. Org. Lett.2015, 17, 1316.

25 _{Luo, J.; Zhang, J. ACS Catal.2016, 6, 873.}

26 _{Butters, M.; Harvey, J. N.; Jover, J.; Lennox, A. J. J.; Lloyd-Jones, G. C., Murray, P. M.} Angew. Chem. Int. Ed.2010, 49, 5156.

28 _{Tada, M.; Yokoi, Y. J. Heterocyclic Chem. 1989, 26, 45.} 29 _{Atack, T. C.; Cook, S. P. J. Am. Chem. Soc.2016, 138, 6139.}

30 _{a) Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A. J. Med. Chem.}

2015, 58, 8315. (b) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev.

2008, 37, 320.

31 _{Murphy-Benenato, K. E.; Olivier, N.; Choy, A.; Ross, P. L.; Miller, M. D.; Thresher, J.; Gao,} N.; Hale, M. R. ACS Med. Chem. Lett.2014, 5, 1213.

32 _{a) Li, G. -X.; Morales-Rivera, C. A.; Wang, Y.; Gao, F.; He, G.; Liu, P.; Chen, G. Chem. Sci.}

2016, 7, 6407. (b) Siddaraju, Y.; Lamani, M.; Prabhu, K. R. J. Org. Chem.2014, 79, 3856. 33 _{(a) Sammes, P. G.; Yahioglu, G. Chem. Soc. Rev.1994, 23, 327. (b) Sammes, P. G.; Yahioglu,}

G. Chem. Soc. Rev.1994, 23, 327.

34 _{Gianatassio, R.; Kawamura, S.; Eprile, C. L.; Foo, K.; Ge, J.; Burns, A. C.; Collins, M. R.;} Baran, P. S. Angew. Chem. Int. Ed.2014, 53, 9851.

35 _{Venditto, V. J.; Simanek, E. E. Mol. Pharm.2010, 7, 307.}

36 _{(a) Mansaray, H. B.; Rowe, A. D. L.; Phillips, N.; Niemeyer, J.; Kelly, M.; Addy, D. A.; Bates,}

J. I.; Aldridge, S. Chem. Comm.2011, 47, 12295. (b) Tarakeshwar, P.; Lee, S. J.; Lee, J. Y.; Kim, K. S. J. Phys. Chem. B.1999, 103, 184.

37 _{(a) Ren, J.; Cramer, C. J.; Squires, R. R. J. Am. Chem. Soc.1999, 121, 2633. (b) Yamamoto,}

H.; Futatsugi, K. Angew. Chem. Int. Ed.2005, 44, 1924.

38 _{Mansaray, H. B.; Rowe, A. D. L.; Phillips, N.; Niemeyer, J.; Kelly, M.; Addy, D. A.; Bates, J.}

I.; Aldridge, S. Chem. Commun.2011, 47, 12295.