to 78% yield). Many aryl bromides function effectively as well, including those that contain functional groups as diverse as ketones, esters, nitriles,
trifluoromethyl groups, and fluorides (14 to 18, 75
to 90% yield). Heteroaromatics, in the form of
differentially substituted bromopyridines, are also
efficient coupling partners (19 to 22, 60 to 85%
yield). Moreover, aryl chlorides are competent
substrates if the arenes, such as pyridines and
pyrimidines, are electron-deficient (23 and 24,
64 and 65% yield). Only products 15 and 19 in
Fig. 3 would be accessible by using our previously
reported photoredox arylation strategy. Moreover, we are unaware of the general use of
Csp3-bearing carboxylic acids as reaction substrates in transition metal catalysis, an illustration of the tremendous scope expansion that is
attainable by using this dual catalysis technology. These reactions are typically complete in 72
hours at larger scale and 48 hours on smaller
scale (see supplementary text).
Next, we investigated the nature of the carboxylic acid coupling partner, as highlighted in
Fig. 4A. A wide variety of a-amino acids function effectively in this protocol, including various
N-Boc and N-benzyl carbamoyl (N-Cbz) protected
heterocycles (25 to 27, 61 to 93% yield). Acyclic
a-amino acids, containing indole, ester, and thio-ether functionalities, are also readily tolerated (28
to 32, 72 to 91% yield). a-oxycarboxylic acids can
function as proficient coupling partners, producing
a-arylated ethers in high yield over a single step
(33, 82% yield). Moreover, we have also found
that various phenyl acetic acid substrates function in this coupling protocol with high efficiency
(>78% yield, see supplementary text).
To further demonstrate the utility of this dual-
catalysis strategy, we sought to demonstrate the
direct functionalization of Csp3–H bonds with
coupling partners derived from aryl or alkyl
halides. Given that our decarboxylation-arylation
mechanism involves the rapid addition of an
a-amino radical to a Ni(II) salt, we sought to gen-
erate an analogous a-nitrogen carbon–centered
radical via a photoredox-driven N-phenyl (N-Ph)
oxidation, a-C–H deprotonation sequence using
aniline-based substrates (18). We presumed that
this photomediated N-Ph oxidation mechanism
would provide an alternative pathway to the open-
shell carbon intermediate (corresponding to 4,
Fig. 2) and should similarly intercept the puta-
tive Ni(II) intermediate 8. Assuming that the
remaining dual-catalysis mechanism would be
analogous to that shown in Fig. 2, we expected
that a range of direct Csp3–H functionalization
protocols should be possible. Indeed, we were able
to demonstrate that dimethylaniline undergoes
a-amine coupling with a variety of aryl halides in
the presence of Ir[dF(CF3)ppy]2(dtbbpy)PF6 and
NiCl2•glyme (Fig. 4B). Electron-deficient and
electron-rich iodoarenes give moderate to high
yields (34 to 36, 72 to 93% yield). Moreover, aryl
bromides are competent coupling partners, en-
abling the installation of medicinally important
heterocyclic motifs (37, 60% yield). Last, control
experiments have revealed that the combination
of light, photoredox catalyst 1, and the NiCl2•dtbbpy
complex is essential for product formation in all
examples listed in Figs. 3 and 4. This reaction
represents a powerful foray into direct C–H acti-
vation using orthogonal cross-coupling reactivity.
REFERENCES AND NOTES
1. D. A. Nicewicz, D. W. C. MacMillan, Science 322, 77–80 (2008).
2. M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am.
Chem. Soc. 130, 12886–12887 (2008).
3. J. M. R. Narayanam, J. W. Tucker, C. R. J. Stephenson, J. Am.
Chem. Soc. 131, 8756–8757 (2009).
4. D. S. Hamilton, D. A. Nicewicz, J. Am. Chem. Soc. 134,
5. M. T. Pirnot, D. A. Rankic, D. B. C. Martin, D. W. C. MacMillan,
Science 339, 1593–1596 (2013).
6. M. R. Netherton, G. C. Fu, Adv. Synth. Catal. 346, 1525–1532
7. A. Rudolph, M. Lautens, Angew. Chem. Int. Ed. 48,
8. The successful merger of photoredox and transition metal
catalysis has been demonstrated for the specific installation
of unique functionality (e.g., CF3) (9–14).
9. M. Osawa, H. Nagai, M. Akita, Dalton Trans. 2007, 827–829
10. D. Kalyani, K. B. McMurtrey, S. R. Neufeldt, M. S. Sanford,
J. Am. Chem. Soc. 133, 18566–18569 (2011).
11. Y. Ye, M. S. Sanford, J. Am. Chem. Soc. 134, 9034–9037 (2012).
12. M. Rueping et al., Chemistry 18, 5170–5174 (2012).
13. B. Sahoo, M. N. Hopkinson, F. Glorius, J. Am. Chem. Soc. 135,
14. X. Z. Shu, M. Zhang, Y. He, H. Frei, F. D. Toste, J. Am.
Chem. Soc. 136, 5844–5847 (2014).
15. S. Biswas, D. J. Weix, J. Am. Chem. Soc. 135, 16192–16197
16. S. L. Zultanski, G. C. Fu, J. Am. Chem. Soc. 135, 624–627
17. Z. Zuo, D. W. C. MacMillan, J. Am. Chem. Soc. 136, 5257–5260
18. A. McNally, C. K. Prier, D. W. C. MacMillan, Science 334,
19. T. J. A. Graham, J. D. Shields, A. G. Doyle, Chem. Sci. 2, 980
20. K. T. Sylvester, K. Wu, A. G. Doyle, J. Am. Chem. Soc. 134,
21. J. D. Shields, D. T. Ahneman, T. J. A. Graham, A. G. Doyle,
Org. Lett. 16, 142–145 (2014).
22. M. S. Lowry et al., Chem. Mater. 17, 5712–5719
23. M. Durandetti, M. Devaud, J. Perichon, New J. Chem. 20, 659
24. Y. H. Budnikova, J. Perichon, D. G. Yakhvarov, Y. M. Kargin,
O. G. Sinyashin, J. Organomet. Chem. 630, 185–192
25. C. Amatore, A. Jutand, Organometallics 7, 2203–2214
The authors are grateful for financial support provided by the
NIH General Medical Sciences (grants NIHGMS R01 GM103558-01
and R01 GM100985-01) and gifts from Merck, Amgen, Eli Lilly,
and Roche. Z.Z. and L.C. are grateful for postdoctoral fellowships
from the Shanghai Institute of Organic Chemistry. The authors
thank G. Molander and co-workers for graciously offering to
concurrently publish a related study that was submitted slightly
ahead of our own.
Material and Methods
Tables S1 and S2
1 May 2014; accepted 27 May 2014
Published online 5 June 2014;
Stellar activity masquerading as
planets in the habitable zone of the
M dwarf Gliese 581
Paul Robertson,1,2 Suvrath Mahadevan,1,2,3 Michael Endl,4 Arpita Roy1,2,3
The M dwarf star Gliese 581 is believed to host four planets, including one (GJ 581d) near
the habitable zone that could possibly support liquid water on its surface if it is a rocky
planet. The detection of another habitable-zone planet—GJ 581g—is disputed, as its
significance depends on the eccentricity assumed for d. Analyzing stellar activity using the
Ha line, we measure a stellar rotation period of 130 T 2 days and a correlation for Ha
modulation with radial velocity. Correcting for activity greatly diminishes the signal of GJ
581d (to 1.5 standard deviations) while significantly boosting the signals of the other
known super-Earth planets. GJ 581d does not exist, but is an artifact of stellar activity
which, when incompletely corrected, causes the false detection of planet g.
At a distance of 6.3 parsecs, the M dwarf star Gliese 581 (GJ 581) is believed to host a system of planets discovered using the Doppler radial velocity (RV) technique (1–3) and a debris disk (4). It is considered a local
analog to compact M dwarf planetary systems
found by the Kepler spacecraft (5, 6).
Although the periods and orbital parameters
of the inner planets b (P = 5.36 days) and c (P =
12.91 days) are unchanged since their initial
discovery (1, 2), the period of planet d was re-
vised from 82 to 66 days (2, 3) upon the dis-
covery of a fourth planet e (P = 3.15 days). Using a
combination of data from the High Accuracy
Radial Velocity Planet Searcher (HARPS) spec-
trograph and the High Resolution Echelle Spec-
trometer (HIRES), planets f (P = 433 days) and g
(P = 36.5 days) were reported (7), and their ex-
istence promptly questioned (8) using addi-
tional data from HARPS. Although the reported
440 25 JULY 2014 • VOL 345 ISSUE 6195
RESEARCH | REPORTS