Catalyst-controlled selectivity in the C-H borylation of methane and ethane

Article abstract of DOI:10.1126/science.aad9289

The C-H bonds of methane are generally more kinetically inert than those of other hydrocarbons, reaction solvents, and methane functionalization products.Thus, developing strategies to achieve selective functionalization of CH₄ remains a major

Full text of DOI:10.1126/science.aad9289

RESEARCH
◥
functionalization of CH4 in the presence of solvent
and CH3X remains a challenging problem (10–14).
We sought to identify a methane C–H function-
alization process in which selectivity (both for
CH4 versus CH3X functionalization and for CH4
versus solvent C–H functionalization) could be
tuned through modification of the homogeneous
transition-metal catalyst. To accomplish this goal,
we focused on the catalytic C–H borylation of meth-
ane with B2pin2 (Fig. 1A). Over the past 15 years,
there has been tremendous progress in the devel-
opment of transition-metal catalysts for the C–H
borylation of liquid alkane substrates. Catalysts
based on iridium (Ir) (18, 19), rhodium (Rh) (20–22),
rhenium (Re) (23), and ruthenium (Ru) (24) have
been reported for liquid alkane C–H borylation, typ-
ically by using the alkane substrate as the solvent
and B2pin2 as the borylating reagent (19, 21, 23–25).
With the vast majority of liquid alkane substrates,
the selectivity of C–H borylation is dominated by
steric factors, with terminal (primary) C(sp3)–H
bonds undergoing selective functionalization over
secondary or tertiary C–H sites (25, 26). This se-
lectivity has been reported to be largely indepen-
dent of the nature of the transition-metal catalyst.
For example, the C–H borylation of n-alkanes
(n-CnH2n+2) with B2pin2 affords 1-Bpin-CnH2n+1
as the sole detectable product with Ir-, Rh-, Re-,
and Ru-based catalysts (18, 20, 23, 24).
In certain contexts, the introduction of a Bpin
substituent has been shown to electronically acti-
vate adjacent C–H bonds toward further C–H
borylation by rendering them more acidic (27, 28).
This electronic activation has been best studied
in the context of benzylic substrates, in which the
C–H borylation of 1°-benzylic C–H bonds is often
slower than that of the 2° a-boryl benzylic C–H
bonds of the products (29, 30). However, the inter-
play between these steric and electronic effects
has not been extensively explored in the C–H
borylation literature, especially as a function of
catalyst metal identity. As discussed below, these
REPORTS
C–H BOND ACTIVATION
Catalyst-controlled selectivity in
the C–H borylation of methane
and ethane
Amanda K. Cook, Sydonie D. Schimler, Adam J. Matzger, Melanie S. Sanford*
The C–H bonds of methane are generally more kinetically inert than those of other
hydrocarbons, reaction solvents, and methane functionalization products. Thus, developing
strategies to achieve selective functionalization of CH4 remains a major challenge. Here, we
report transition metal–catalyzed C–H borylation of methane with bis-pinacolborane (B2pin2) in
cyclohexane solvent at 150°C under 2800 to 3500 kilopascals of methane pressure. Iridium,
rhodium, and ruthenium complexes all catalyze the reaction. Formation of mono- versus
diborylated methane is tunable as a function of catalyst, with the ruthenium complex providing
the highest ratio of CH3Bpin to CH2(Bpin)2. Despite the high relative concentration of
cyclohexane, minimal quantities of borylated cyclohexane products are observed. Furthermore,
all three metal complexes catalyze borylation of methane with >3.5:1 selectivity over ethane.
ver the past 50 years, numerous homoge-
neous transition-metal catalysts have been
developed for the C–H functionalization
of liquid alkanes [for example, via de-
hydrogenation (1), oxygenation (2), carbon-
of methane are stronger than those of most liq-
uid alkanes [the C–H bond dissociation energies
(BDEs) of methane, n-hexane (1°C–H), and cyclo-
hexane are 105, 101, and 99.5 kcal/mol, respective-
ly (15, 16)]. As such, methane C–H bond cleavage
is prohibitively slow with many catalysts. Second,
homogeneous alkane functionalization reactions
are typically conducted by using neat alkane as
the solvent (4, 5, 14), so the use of methane gas
as a substrate poses challenges with respect to
identifying a compatible reaction solvent (12, 17).
Last, the reaction solvent and the CH3X products
of methane functionalization typically contain
more reactive C–H bonds than those of CH4. As
such, developing strategies to achieve selective
O
ylation (3), borylation (4–7), and C-, N-, and O-atom
insertion (8, 9)]. However, relatively few of these
catalysts have been translated to analogous re-
actions of methane (10–14). This is largely due
to the particular challenges associated with meth-
ane C–H functionalization. First, the C–H bonds
Department of Chemistry, University of Michigan, 930 North
University Avenue, Ann Arbor, MI 48109, USA.
*Corresponding author. E-mail: mssanfor@umich.edu
Fig. 1. Reactivity and selectivity challenges in the C–H borylation of methane. (A) Proposed methane C–H borylation reaction. (B) Challenges with
selectivity in methane C–H borylation.
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issues are expected to be particularly salient in
the context of methane C–H borylation (Fig. 1B).
In 2005, Hall and co-workers reported density
functional theory (DFT) calculations that suggest
that Cp*Rh complexes (Cp*, pentamethylcyclo-
pentadienyl) should be capable of catalyzing the
C–H borylation of CH4 (22). Despite these encour-
aging computational results, there have been no
subsequent experimental studies establishing the
feasibility and/or exploring the selectivity of meth-
ane C–H borylation with these or any other catalysts.
In a methane C–H borylation reaction, three major
C–H bond–containing molecules will be present
in solution: methane, CH3Bpin, and solvent (cyclo-
hexane) (Fig. 1B). Among these three molecules,
methane has the most sterically accessible C–H
bonds, CH3Bpin has the most electronically ac-
tivated (acidic) C–H bonds, and the reaction sol-
vent, cyclohexane, is statistically favored because
of its high concentration. Our studies sought to
(i) experimentally establish the feasibility of metal-
catalyzed methane C–H borylation; (ii) determine
which factor (or factors) dominate selectivity in
this transformation (sterics, electronics, or statis-
tics); and (iii) probe whether different catalysts
can be used to tune the selectivity of the reaction.
We selected Rh complex 1 for our initial in-
vestigations of methane C–H borylation on the
basis of Hall and co-workers’DFT calculations, which
predicted a relatively low barrier for CH4 acti-
vation with this complex (22). The initial reactions
were conducted in a Parr high-pressure batch
reactor (45 mL volume) at 150°C, using 1.5 mole
percent (mol %) of 1, 3500 kPa of methane, and
0.89 mmol of B2pin2 as the limiting reagent (31).
As discussed above, the choice of solvent is par-
ticularly critical because any C–H bonds in the
solvent must be less reactive with 1 than those of
CH4. Thus, we first examined solvents without C–H
bonds [perfluoromethylcyclohexane (PFMCH) and
perfluorohexane (PFH)]. However, modest yields
of methane C–H borylation products were ob-
tained (Table 1, entries 1 and 2), likely because of
the low solubility of the Rh catalyst in these me-
dia. We next examined cyclopentane (c-C5H10)
and cyclohexane (c-C6H12) as solvents (Table 1,
entries 3 and 4). These cycloalkanes are both
known to be poor substrates for Rh-catalyzed
C–H borylation (6, 20, 21) because the 2°C–H
bonds are relatively sterically congested and
weakly acidic (32). Cyclohexane proved to be op-
timal, affording CH3Bpin in 74% yield with only
traces (~2%) of the solvent C–H borylation product
c-C6H11Bpin (Table 1, entry 4). Under these condi-
tions, high selectivity was also observed for the
mono-borylation of methane [ratio of CH3Bpin to
bis-borylated CH2(Bpin)2 was 10:1]. Increasing the
loading of catalyst 1 to 3 mol % resulted in 99% yield
of CH3Bpin, while maintaining excellent selectiv-
ity for CH3Bpin over c-C6H11Bpin and CH2(Bpin)2
(entry 6). Lowering the catalyst loading to 0.75
mol % resulted in decreased yield of CH3Bpin
(51%) but increased turnover number (68 turn-
overs) (entry 5) relative to the standard conditions.
We next examined Ir and Ru complexes 2/3 and
4as potential catalysts for methane C–Hborylation.
These complexes were selected on the basis of their
Table 1. Methane C–H borylation catalyzed by 1.
Entry
Mol % 1
Solvent
Yield*
TON
CH3Bpin:solventBpin*
CH3Bpin:CH2(Bpin)2*
1
1.5
1.5
1.5
PFMCH
<1%
.............................................................................................<...1.....................................................................................................................
na†
na†
2
3
PFH
26%
69%
.............................................................................................1..7......................................................................................................................
na†
8:1
c-C5H10
46
49
68
33
...................................................................................................................................8...:.1..............................................................................
10:1
10:1
18:1
9:1
.4...............................................................................................................................4...8...:.1..............................................................................
1.5
c-C6H12
74%
.5.......................................................................5...1..%........................................................................................................................................
0.75
c-C6H12
46:1
.6...............................................................................................................................5...9...:.1..............................................................................
3
c-C6H12
99%
*Yields and ratios of all products were determined by means of gas chromatography–flame ionization
detector (GC-FID) and are based on B2pin2 as the limiting reagent. †na, not applicable.
Table 2. Impact of catalyst on the yield and selectivity of methane C–H borylation.
Entry Catalyst Time (hours) Yield* TON CH3Bpin:CyBpin* CH3Bpin:CH2(Bpin)2*
1
.........................2.../..3.......................................................................................................................................................................................
14
45%
15
3:1
4:1
2
4
..........................................................1.4........................6...7...%...............2...2...........................8...3...:.1............................................2...1..:.1......................
3
..........................4...†........................................................................................................................................................................................
6
50%
17
82:1
31:1
4
1†
1
...................................................................................5...4...%............................................................................................................................
18
36:1
20:1
*Yields and ratios of all products were determined by means of GC-FID and are based on B2pin2 as the
limiting reagent.
†Reactions stopped before completion in order to compare selectivity at similar yields.
Fig. 2. Time studies
showing formation
of CH3Bpin using
2800 kPa of CH4. Rh
complex 1 is indicated
with red squares, Ir
complex 2/3 with blue
circles, and Ru
complex 4 with green
triangles.
known catalytic activity for the C–H borylation of
liquid alkanes (18, 19, 24, 33, 34). Under the opti-
mal conditions for catalyst 1, the combination of
Ir complex 2 and ligand 3 (18) afforded moderate
yield (45%) of CH3Bpin, whereas Ru complex 4
provided 67% yield (Table 2, entries 1 and 2). To
more quantitatively compare these three catalysts,
reaction progress was monitored as a function of
time, and the results are shown in Fig. 2. These
studies show that all of the reactions achieve a
maximum yield within 10 hours. However, the ini-
tial reaction rate with Rh catalyst 1 is approximate-
ly four times faster than that with 2/3. Furthermore,
4 displays a lengthy induction period (~ 2 hours),
suggesting that it serves as a precatalyst for this
transformation (24, 35).
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| REPORTS
Fig. 3. Evaluation
of the selectivity
in CH4/CH3Bpin
borylation. (A to C) Re-
action time profiles
(top) for (A) Ir catalyst
2/3, (B) Rh catalyst 1,
and (C) Ru catalyst 4.
Red squares (left y axes)
represent formation of
CH2(Bpin)2, and blue
circles (right y axes)
represent formation of
CH3Bpin. CH3Bpin:
CH2(Bpin)2 ratios at
early time points, relative
rates, and DDG‡ values
for the three catalyst
systems are given below
their respective time
profile graphs.
onset, we can estimate kCH4/kCH3Bpin (and thus
approximate DDG‡) for the C–H borylation of CH4
versus CH3Bpin for each catalyst (complete details
of these calculations are provided in the supple-
mentary materials). As shown in the bottom of
Fig. 3, positive DDG‡ values are observed for cat-
alysts 1 and 2/3, reflecting faster C–H borylation
of CH3Bpin versus CH4. The values of DDG‡ are
estimated as 0.53 and 2.48 kcal/mol for 1 and 2/3,
respectively. In contrast, Ru catalyst 4 shows a
reversal in selectivity, exhibiting a preference for
CH4 over CH3Bpin, with an estimated DDG‡ of
–0.5 kcal/mol.
The relative reactivity of methane and ethane
is another important issue (given that ethane is
the secondmost abundant component of natural
gas) but is rarely addressed in alkane C–H func-
tionalization reactions. In the few reported sys-
tems in which this has been studied, ethane is
usually found to be much more reactive (17, 37–39).
As shown in Fig. 4A, catalysts 1, 2/3, and 4 all
catalyze the C–H borylation of ethane at 150°C in
cyclohexane. Again, ethane borylation occurs in
preference to cyclohexane borylation and shows
a similar dependence on metal catalyst as with
methane, with selectivities ranging from 5:1 (with
2/3) to >100:1 (with 4).
To probe catalyst selectivity for methane versus
ethane, known molar quantities of each gas were
added to the high-pressure reactor. The reactions
were run to complete conversion of B2pin2, and
the ratio of CH3Bpin to CH3CH2Bpin was deter-
mined with each catalyst. These ratios were then
corrected for the number of C–H bonds in each
substrate as well as the relative solubilities of the
two gases (36). As shown in Fig. 4B, all three cat-
alysts exhibit a >3.5:1 preference for the C–H
borylation of methane relative to ethane, which
is consistent with sterically controlled selectivity.
Additionally, the level of selectivity varies with
the catalyst. The Ir catalyst 2/3 and Ru catalyst 4
both react approximately fourfold faster with
methane C–H bonds, whereas 1 is more selective
for methane (approximately sixfold faster). These
Fig. 4. Comparison of catalysts for ethane borylation. (A) Batch ethane borylation results for catalysts
2/3, 1, and 4. (B) Methane and ethane one-pot competition. Selectivity factor is the preference for meth-
ane over ethane borylation corrected for statistics and solubility.
In the Table 2 data, the choice of catalyst has a
major impact on the selectivity of C–H borylation,
both for methane versus cyclohexane and for
methane versus CH3Bpin. In particular, Rh and
Ru catalysts 1 and 4 exhibit much higher selec-
tivity for CH4 than does the Ir catalyst system 2/3.
This effect is observed even when the reactions
are stopped at similar yield of CH3Bpin (~50% yield;
Table 2, entries 1, 3, and 4 for comparison). The
ratio of CH3Bpin to c-C6H11Bpin ranged from 82:1
(with catalyst 4) to 3:1 (with catalyst 2/3). Simi-
larly, the CH3Bpin to CH2(Bpin)2 ratio ranged from
31:1 (with catalyst 4) to 4:1 (with catalyst 2/3). These
results indicate that tuning of the catalyst struc-
ture can be used to control this undesired over-
functionalization reaction.
(36) and CH3Bpin (0.13 M, 1 equivalent relative to
B2pin2) with each of the catalysts 1, 2/3, and 4.
The time course of each reaction is shown in Fig.
3. The yield of CH3Bpin (Fig. 3, blue circles, right
y axes) represents the additional CH3Bpin formed
from the C–H borylation of CH4 (measured in
excess of 100%, given the CH3Bpin equivalent
added at the outset), whereas the yield of CH2
(Bpin)2 (Fig. 3, red squares, left y axes) represents
the product of C–H borylation of CH3Bpin.
With Ir catalyst 2/3 (Fig. 3A), the quantity of
diborylated product present exceeds that of
CH3Bpin at all time points. In contrast, the con-
centration of CH3Bpin is much greater than that
of CH2(Bpin)2 throughout the reactions catalyzed
by Rh complex 1 and Ru complex 4 (Fig. 3, B and
C, respectively). Using the ratio of CH3Bpin:CH2
(Bpin)2 obtained at early time points and the
concentrations of CH4 and CH3Bpin added at the
To more quantitatively evaluate selectivity
as a function of catalyst, we conducted compe-
tition experiments between CH4 (3500 kPa, 1.1 M)
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results further highlight the impact of catalyst
on both reactivity and selectivity in the C–H
borylation of light alkanes.
37. M. Lin, T. E. Hogan, A. Sen, J. Am. Chem. Soc. 118, 4574–4580 (1996).
38. O. Demoulin, B. Le Clef, M. Navez, P. Ruiz, Appl. Catal. A Gen.
344, 1–9 (2008).
purchased with funds from the NSF, under the CCI CENTC Phase II
Renewal, CHE-1205189. We gratefully acknowledge D. Samblanet
for assistance with the gas solubility measurements. The University
of Michigan has filed for a provisional patent on this work.
39. P. O. Graf, B. L. Mojet, L. Lefferts, Appl. Catal. A Gen. 346,
Overall, we have demonstrated that catalyst
structure has a major impact on reaction rates
and selectivities in the C–H borylation of meth-
ane. Over-functionalization of the initial product,
CH3Bpin, can be limited through the appropriate
selection of catalyst. These results open up ex-
citing possibilities for catalyst design (to further
modulate reactivity and selectivity in methane
C–H borylation) as well as the application of the
concepts delineated here for other light alkane
C–H functionalization reactions.
90–95 (2008).
SUPPLEMENTARY MATERIALS
ACKNOWLEDGMENTS
www.sciencemag.org/content/351/6280/1421/suppl/DC1
Materials and Methods
Supplementary Text
Figs. S1 to S19
Tables S1 to S14
The work conducted by A.K.C. (primarily involving evaluation
of catalysts 1 and 2/3) was supported by NSF under the Centers for
Chemical Innovation (CCI) Center for Enabling New Technologies
through Catalysis (CENTC) Phase II Renewal, CHE-1205189. The
work conducted by S.D.S. (primarily involving evaluation of catalyst
4 and gas solubility measurements) was supported by the U.S.
Department of Energy Office of Basic Energy Sciences (contract DE-
FG02-08ER 15997). The Parr reactors used in this work were
References (40–57)
24 November 2015; accepted 18 February 2016
10.1126/science.aad9289
REFERENCES AND NOTES
C–H BOND ACTIVATION
1. J. Choi, A. H. R. MacArthur, M. Brookhart, A. S. Goldman,
Chem. Rev. 111, 1761–1779 (2011).
2. A. E. Shilov, G. B. Shul’pin, Chem. Rev. 97, 2879–2932 (1997).
3. T. Sakakura, T. Sodeyama, K. Sasaki, K. Wada, M. Tanaka,
J. Am. Chem. Soc. 112, 7221–7229 (1990).
4. T. Ishiyama, N. Miyaura, J. Organomet. Chem. 680, 3–11
(2003).
Catalytic borylation of methane
Kyle T. Smith,1 Simon Berritt,1 Mariano González-Moreiras,1 Seihwan Ahn,2,3
5. I. A. I. Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy,
J. F. Hartwig, Chem. Rev. 110, 890–931 (2010).
Milton R. Smith III,4* Mu-Hyun Baik,2,3* Daniel J. Mindiola1*
6. J. F. Hartwig, Chem. Soc. Rev. 40, 1992–2002 (2011).
7. J. F. Hartwig, Acc. Chem. Res. 45, 864–873 (2012).
8. H. M. L. Davies, J. R. Manning, Nature 451, 417–424 (2008).
9. D. Mansuy, Coord. Chem. Rev. 125, 129–141 (1993).
10. H. Schwarz, Angew. Chem. Int. Ed. 50, 10096–10115 (2011).
11. V. N. Cavaliere, B. F. Wicker, D. J. Mindiola, Adv. Organomet.
Chem. 60, 1–47 (2012).
12. N. J. Gunsalus, M. M. Konnick, B. G. Hashiguchi, R. A. Periana,
Isr. J. Chem. 54, 1467–1480 (2014).
13. P. Tang, Q. Zhu, Z. Wu, D. Ma, Environ. Sci. 7, 2580–2591 (2014).
14. A. Caballero, P. J. Pérez, Chem. Soc. Rev. 42, 8809–8820 (2013).
15. D. R. Lide, CRC Handbook of Chemistry and Physics (CRC
Press, ed. 96, 2015).
Despite steady progress in catalytic methods for the borylation of hydrocarbons, methane has
not yet been subject to this transformation. Here we report the iridium-catalyzed borylation of
methane using bis(pinacolborane) in cyclohexane solvent. Initially, trace amounts of borylated
products were detected with phenanthroline-coordinated Ir complexes. A combination of
experimental high-pressure and high-throughput screening, and computational mechanism
discovery techniques helped to rationalize the foundation of the catalysis and identify improved
phosphine-coordinated catalytic complexes. Optimized conditions of 150°C and 3500-
kilopascal pressure led to yields as high as ~52%, turnover numbers of 100, and improved
chemoselectivity for monoborylated versus diborylated methane.
16. S. J. Blanksby, G. B. Ellison, Acc. Chem. Res. 36, 255–263 (2003).
17. A. Caballero et al., Science 332, 835–838 (2011).
18. C. W. Liskey, J. F. Hartwig, J. Am. Chem. Soc. 134,
12422–12425 (2012).
19. C. W. Liskey, J. F. Hartwig, J. Am. Chem. Soc. 135, 3375–3378 (2013).
20. H. Chen, S. Schlecht, T. C. Semple, J. F. Hartwig, Science 287,
1995–1997 (2000).
21. C. S. Wei, C. A. Jiménez-Hoyos, M. F. Videa, J. F. Hartwig,
M. B. Hall, J. Am. Chem. Soc. 132, 3078–3091 (2010).
22. J. F. Hartwig et al., J. Am. Chem. Soc. 127, 2538–2552
(2005).
23. H. Chen, J. F. Hartwig, Angew. Chem. Int. Ed. 38, 3391–3393
(1999).
24. J. M. Murphy, J. D. Lawrence, K. Kawamura, C. Incarvito,
J. F. Hartwig, J. Am. Chem. Soc. 128, 13684–13685 (2006).
25. Q. Li, C. W. Liskey, J. F. Hartwig, J. Am. Chem. Soc. 136,
8755–8765 (2014).
26. J. D. Lawrence, M. Takahashi, C. Bae, J. F. Hartwig, J. Am.
Chem. Soc. 126, 15334–15335 (2004).
27. B. A. Vanchura II et al., Chem. Commun. (Camb.) 46,
7724–7726 (2010).
28. H. Tajuddin et al., Chem. Sci. 3, 3505–3515 (2012).
29. S. Shimada, A. S. Batsanov, J. A. K. Howard, T. B. Marder,
Angew. Chem. Int. Ed. 40, 2168–2171 (2001).
ctivation of methane is challenging because
it is nonpolar, has strong sp3 C–H bonds, is
sparingly soluble in both polar and non-
polar solvents, and has very high ioniza-
tion energies and very low triple, boiling,
tions with methane have not been thoroughly
explored, despite this reaction being known for
more than a decade. Fundamentally important is
that the methyl-derived product is arguably a
form of a mildly nucleophilic methyl transfer re-
agent, which complements the chemistry observed
in electrophilic activation reactions in Shilov-type
chemistry (9). Theory predicts that borylation of
hydrocarbons with a borane (Eq. 1) is thermo-
neutral, whereas the weaker B–B bond in diboron
reagents provides an enthalpic driving force of
at least 12 kcal/mol, as shown in Eq. 2 (18). These
considerations led us to pursue the catalytic
borylation of methane using diboron reagents
such as B2pin2 (pin = pinacolate).
A
and flashing points (1–8). Homogeneous catalysts
that convert methane to products that could be
used as liquid fuels are known, but these sys-
tems often require strong electrophiles and, in
some cases, superacids and/or powerful oxidants
(1, 2, 9–17). Chemoselectivity is another limita-
tion in methane activation and functionalization.
For instance, H3C-R (R = functional group) pro-
ducts resulting from methane activation and func-
tionalization have more reactive C–H bonds than
methane itself, hence often resulting in poor se-
lectivity, overfunctionalization, and overoxidation.
The pioneering work by Hartwig, Marder, and
Smith on C–H bond borylation inspired our in-
vestigation into the catalytic functionalization of
methane using a similar approach (18). Whereas
stoichiometric and catalytic borylations of al-
kanes show marked selectivity for monoborylation
of terminal methyl groups (18), analogous reac-
H3C‐H þ H‐BðORÞ2 → H3C‐BðORÞ2 þ
30. M. A. Larsen, C. V. Wilson, J. F. Hartwig, J. Am. Chem. Soc. 137,
8633–8643 (2015).
H‐H DHo ¼ −1 to þ1 kcal=mol
ð1Þ
31. These initial conditions were selected on the basis of (i) published
conditions for alkane borylation reactions (20, 21, 24, 26) as well as
(ii) the fixed volume of our Parr high-pressure reactor.
32. The 1-catalyzed background reaction of c-C5H10 and c-C6H12
with B2pin2 in the absence of methane afforded 20.3 and 4.2%
yield of the solvent C–H borylation products, respectively.
33. G. A. Chotana et al., Chem. Commun. (Camb.) 38, 5731–5733
(2009).
34. P. Nguyen, H. P. Blom, S. A. Westcott, N. J. Taylor,
T. B. Marder, J. Am. Chem. Soc. 115, 9329–9330 (1993).
35. All three of these reactions passed the Hg drop test (supplemen-
tary materials), which is consistent with homogeneous catalysis.
H3C‐H þ ðROÞ2B‐BðORÞ2 → H3C‐BðORÞ2 þ
H‐BðORÞ2 DHo ¼ −13 kcal=mol ð2Þ
Iridium systems are particularly promising for
C-H activation of methane (1, 2), and some of the
most active borylation catalysts use this transition
metal (18). Therefore, we focused our attention
on the commercially available iridium reagents
[Ir(COD)(m-Cl)]2, [Ir(COD)(m-OMe)]2 (COD = 1,5-
cyclooctadiene), and (MesH)Ir(Bpin)3 (MesH =
mesitylene) (19), modifying them with a range of
1Department of Chemistry, University of Pennsylvania, 231
South 34th Street, Philadelphia, PA 19104, USA. 2Institute for
Basic Science–Center for Catalytic Hydrocarbon
Functionalizations, Daejeon, Korea. 3Department of Chemistry,
Korea Advanced Institute of Science and Technology, Daejeon,
Korea. 4Department of Chemistry, Michigan State University,
578 South Shaw Lane, East Lansing, MI 48824, USA.
36. The concentrations of methane and ethane under the reaction
conditions were determined by using Raman spectroscopic
analysis of solutions of CH4 or CH3CH3 in C6D12 (supplementary
materials).
*Corresponding author. E-mail: smithmil@msu.edu (M.R.S.);
mbaik2805@kaist.ac.kr (M.-H.B.); mindiola@sas.upenn.edu (D.J.M.)
1424 25 MARCH 2016 • VOL 351 ISSUE 6280
sciencemag.org SCIENCE

Catalyst-controlled selectivity in the C−H borylation of methane and
ethane
Amanda K. Cook et al.
Science 351, 1421 (2016);
DOI: 10.1126/science.aad9289
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