Journal of the American Chemical Society
Page 4 of 5
Science and Engineering for insightful discussions and a generous
to its radical anion II. Fragmentation followed by re-
combination (supported by a radical clock experiment,
see SI) with the Fe species III would afford IV, which
upon reductive elimination delivers the final product and
regenerates the low-valent catalyst V. Anion metathesis
with another molecule of organometallic would then
restore the active catalyst I thus closing the catalytic
cycle. Finally, it is worth noting that the kinetics of the
Fe-catalyzed process are extremely rapid with complete
conversion (ca. 75%) being observed within one minute
using substrate 1 (see SI). In comparison, Ni-catalysis of
the same transformation required >12 hours to reach full
conversion (85% yield).
1
2
3
4
5
6
7
8
sample of cubane dimethylester. We are also grateful to Mr. Na-
than Ferrandin for synthesis of starting materials, Mr. Jacob Ed-
wards for initial investigations, and to A. L. Rheingold and M.
Gembicky for X-ray crystallographic analysis.
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Fe(III)+ dppBz (L)
PhMgBr
or Ph2Zn
N
Cy
Ph–Ph
O
L
Fen
3
Cy
O N
N
N
N
reductive
elimination
At
V
Fen
ZnAtBr
I
L
SET
ox. add.
Cy
At
Fen+2
L
O
IV
Cy
O N
L
Fen+1
III
N
II
N
N
radical
recombination
N
– CO2
+
Cy
N
decarboxylative
fragmentation
N
At
Figure 3. Mechanistic hypothesis for Fe-catalyzed between RAE
and arylmetal species.
RAEs can now be employed in a similar manner to alkyl
halides in Fe-catalyzed cross coupling chemistry. To our
knowledge this is the first systematic side-by-side compari-
son of the differences between Ni and Fe catalysts across a
range of substrates to reveal real-world practical ad-
vantages of each in certain contexts. The newly developed
Fe-based system has obvious advantages in terms of ease of
scale-up and sustainability, but several unique and im-
portant differentiating features: near-instantaneous reaction
rates, orthogonality of RAEs to alkyl bromides, applicabil-
ity to tertiary systems including the venerable cubane cou-
pling challenge, and superiority in the coupling of amino
acid and unactivated primary systems.16
ASSOCIATED CONTENT
Supporting Information. Detailed graphical experimental proce-
dures, frequently asked questions, trouble-shooting, extensive
optimization data, analytical data (1H and 13C NMR, MS), and full
citation for ref. 10. X-ray information for compounds 36 (CCDC
1491206), 49 (CCDC 1491208) and 50 (CCDC 1491207). This
material is available free of charge via the Internet at
AUTHOR INFORMATION
Corresponding Authors
E-mail: pbaran@scripps.edu (P.S.B.).
Author Contributions
§ F. T. and J. C. contributed equally to this work.
ACKNOWLEDGMENT
Financial support for this work was provided by NIH (GM-
118176), Bristol-Myers Squibb, Daiichi Sankyo Co., Ltd. (re-
search support to F. T.), postdoctoral fellowships from the Catalan
Government (to J. C.), Austrian Science Fund (to L. W.) and
Shenzhen HIWIN M&E Co. Ltd. (to T. –G. C.). We thank Ke
Chen, Michael Schmidt, Frank Rinaldi and Martin D. Eastgate for
helpful discussions. We thank Dr. Craig M. Williams at Queens-
land University and Dr. John Tsanaktsidis at CSIRO Materials
(16) This chemistry was field-tested in the context of both process (sub-
strates 20 and 21) and medicinal (substrate 36, verified by X-Ray
crystallography) groups at BMS.
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