Angewandte Chemie International Edition
10.1002/anie.201807448
COMMUNICATION
scissions. Scheme 5 shows the results for several alkanes. Thus, providing the highest relative reactivity. Overall, the results are
with hexane as the substrate, secondary sites are more reactive
than primary ones, and among the former, the less hindered
C(2)-H bonds (S5) are more reactive than the other secondary
C(3)-H bonds (S6). With 2,3-dimethylbutane, the tertiary C-H
bond (T2) is also functionalized at a larger extend compared
with the primary C-H bonds (P7), whereas with 2-methylbutane,
the tertiary (T3) > secondary (S7) > primary (P8, P9) trend is
also observed, both primary sites being different as the result of
distinct steric hindrance. But when the steric pressure augments,
such as in the case of 2,4-dimethylpentane, the observed values
of 1.19, 0.28 and 0.74 for P10, S8 and T4, respectively,
assessed Olah’s concerns about the effect of size in the
selectivity. Thus, our experimental data validate Olah’s model at
similar to those observed with methane as the reference.
In conclusion, we have measured the relative reactivity (R
r
)
with methane as the reference of twenty-nine carbon-hydrogen
bonds of fourteen different alkanes acting as (weak)
nucleophiles in their reaction with in situ generated silver-
carbene complexes as the (strong) electrophile. Data collected
with our model system using intermolecular competitions have
shown the lack of a general pattern of reactivity for the reaction
sites. Expansion to copper- and rhodium-based electrophiles,
with cyclohexane as the reference, have shown the same
behavior.
the intramolecular level but demonstrate that its application Acknowledgements
between C-H bonds of different substrates is, as best, in doubt.
Similar log(R
due to the lack of significant reactivity of the corresponding in
situ generated L M=C(H)CO Et electrophiles towards methane
and other gaseous alkanes.
corresponding log(R values using cyclohexane as the
reference (Scheme 6) performing series of competition
experiments between such cycloalkane and the eight liquid
alkanes (C 2n+2, n > 4) shown in Scheme 3. The carbene
insertion reaction (from ethyl diazoacetate) was catalyzed by
r
) values cannot be determined for other metals
We thank MINECO for support with Grants CTQ2017-82893-C2-
1
8
-R, CTQ2014-62234-EXP, CTQ2015-73693-JIN, CTQ2017-
7792-R, Severo Ochoa Excellence Accreditation 2014-2018
n
Thus, we have obtained the
(
SEV-2013-0319), Red Intecat (CTQ2016-81923-REDC). Junta
r
)
de Andalucía is also acknowledged for Grant P12-FQM-1765. R.
G. and A. O. thanks MINECO for FPI and Juan de la Cierva
fellowships, respectively. The CNRS is thanked for support.
a
n
H
Keywords: C-H bond alkane reactivity C-H bond
functionalization alkane nucleophilicity metal-carbene
electrophiles alkane functionalization
[
34]
complexes 1-3, the dirhodium complex [Rh
3
)
4
]
(4)
Cu(thf) (5). Scheme 6 shows
) for those five catalysts (see Supporting
F18,Br3
and the copper complex Tp
the values of log(R
r
Information for details and full list of data). As expected, the
three silver-based electrophiles behave similarly, and followed
the same order previously established with methane as the
reference. However, the use of rhodium or copper brings
significant differences: primary sites are less reactive with the
rhodium- and, more drastically, with the copper-based catalysts
compared to the silver electrophiles. Since 1 and 5 only differ in
[
1]
2]
G. A. Olah, A. Molnár Hydrocarbon Chemistry, 2nd ed; John Wiley &
Sons Inc.: Hoboken, New Jersey, 2003.
[
N. V. Cavaliere, D. J. Mindiola Chem. Sci., 2012, 3, 3356-3365.
A. Caballero, P. J. Pérez Chem. Soc. Rev. 2013, 42, 8809-8820.
Alkane C-H Activation by Single-Site Metal Catalysis; P. J. Pérez, Ed;
Springer: Dordrecht, 2012.
[3]
[4]
x
the metal center, the Tp ligand being the same, it is the nature
[
5]
6]
G. A. Olah, P. Ramaiah, G. K. S. Prakash Proc. Natl. Acad. Sci., 1997,
94, 11783-11785.
[
G. A. Olah, R. Malhotra, S. C. Narang Nitration. Methods and
mechanisms; VCH: New York, 1989.
[
7]
8]
G. A. Olah Angew. Chem., Int. Ed. Engl., 1973, 12, 173-212.
G. A. Olah, G. K. S. Prakash, J. Sommer Superacids; John Wiley and
Sons Inc.: New York, 1985.
[
[
9]
H. Mayr, A. R. Ofial, Acc. Chem. Res. 2016, 49, 952-965.
log(Rr)
1
[10] A. S. Weller, F. M. Chadwick, A. I. McKay Adv. Organomet. Chem.,
016, 66, 223-276.
2
Primary
Secondary
Tertiary
0
,5
0
[11] H. M. Yau, A. I. McKay, H. Hesse, R. Xu, M. He, C. E. G. Holt, E. Ball J.
Am. Chem. Soc., 2016, 138, 281-288.
P4 P5 P7 P8 P9 P10 P11 S3 S4 S5 S6 S7 S8 S9 S10 S11 S12 T2 T3 T4
-
-
-
-
0,5
[
12] H. Mayr, M. Patz Angew. Chem., Int. Ed. Engl., 1994, 33, 938-957.
13] H. Mayr, A. R. Ofial J. Phys. Org. Chem., 2008, 21, 584-595.
-
1
[
1,5
[14] M. Horn, L. H. Schappele, G.e Lang-Wittkowski, H. Mayr, A. R. Ofial
Chem. Eur. J. 2013, 19, 249-263.
-
2
2,5
[15] A. Streitwieser, D. A. Bors, M. J. Kaufman J. Chem. Soc., Chem.
-
3
Commun. 1983, 1394-1395.
th
[16]
K. P. C. Volhardt, Organic Chemistry, 6 Ed., W. H. Freeman, 2010
3,5
TpF18,Br3Ag(thf)
TpF27Ag(thf)
TpF39Ag(thf)
Rh2(OCOCF3)4
TpF18,Br3Cu
[17] A. Caballero, E. Despagnet-Ayoub, M. M. Díaz-Requejo, A. Díaz-
Rodríguez, M. E. Gonzꢀlez-Nꢁꢂez, R. Mello, B. K. Muꢂoz, B. K.; W.
Solo-Ojo, G. Asensio, M. Etienne, P. J. Pꢃrez Science, 2011, 332, 835-
Scheme 6. The effect of the metal in the relative reactivity of C-H bonds of
alkanes, with cyclohexane as the reference.
838.
[
18] M. A. Fuentes, A. Olmos, B. K. Muꢂoz, K. Jacob, M. E. Gonzꢀlez-
Nꢁꢂez, R. Mello, G. Asensio, A. Caballero, M. Etienne, P. J. Pꢃrez
Chem. Eur. J., 2014, 20, 11013-11018.
of the metal that is influencing the reaction outcome. For
secondary sites, the log(R ) values are similar for 1-4, but slightly
r
lower for 5. In the region of the tertiary sites, copper- and silver-
[19] J. A. Flores, N. Komine, K. Pal, B. Pinter, M. Pink, C.-H. Chen, K. G.
Caulton, D. J. Mindiola, ACS Catal., 2012, 2, 2066−2078.
based catalysts show similar behavior, the rhodium catalyst
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