Recyclable Trifluoromethylation Reagents from Fluoroform

Article abstract of DOI:10.1021/jacs.7b05408

We present a strategy to rationally prepare CF₃^- transfer reagents at ambient temperature from HCF_3. We demonstrate that a highly reactive CF₃^- adduct can be synthesized from alkali metal hydride, HCF₃, and borazine Lewis acids in quantitative yield at room temperature. These nucleophilic reagents transfer CF₃^- to substrates without additional chemical activation, and after CF₃ transfer, the free borazine is quantitatively regenerated. These features enable syntheses of popular nucleophilic, radical, and electrophilic trifluoromethylation reagents with complete recycling of the borazine Lewis acid.

Full text of DOI:10.1021/jacs.7b05408

This is an open access article published under an ACS AuthorChoice License, which permits
copying and redistribution of the article or any adaptations for non-commercial purposes.
Communication
pubs.acs.org/JACS
Recyclable Trifluoromethylation Reagents from Fluoroform
Jacob B. Geri and Nathaniel K. Szymczak*
Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, Michigan 48109-1055, United States
S Supporting Information
*
ABSTRACT: We present a strategy to rationally prepare
−
CF3 transfer reagents at ambient temperature from HCF
3.
−
We demonstrate that a highly reactive CF3 adduct can be
synthesized from alkali metal hydride, HCF , and borazine
3
Lewis acids in quantitative yield at room temperature.
−
These nucleophilic reagents transfer CF3 to substrates
without additional chemical activation, and after CF3
transfer, the free borazine is quantitatively regenerated.
These features enable syntheses of popular nucleophilic,
radical, and electrophilic trifluoromethylation reagents
with complete recycling of the borazine Lewis acid.
he trifluoromethyl functional group is widely used in
medicinal chemistry to enhance the bioavailability, lip-
ophilicity, and resistance to oxidative degradation of drug
T
molecules, and these properties have led to its inclusion in many
1
approved drugs. Fluoroform (HCF , <$0.10/mol) is an
3
attractive starting material for CF installation reactions: it is
3
2
nontoxic, widely available, and easily handled. However, even
Figure 1. Challenges in HCF activation (E = electrophile).
3
though >0.5 million metric tons of HCF are produced each year
3
as a byproduct from PTFE manufacturing, it is not used as a CF3
feedstock and is instead incinerated.
3
requires the combination of KHMDS and electrophiles prior to
Unlike methane, which is widely used as a source of the −CH
addition of HCF , which presents an operational challenge. This
3
3
4
group, the use of HCF as a −CF feedstock has presented
strategy is limited by the expense of the required bases, cryogenic
3
3
2
significant challenges. Although HCF has a large C−H bond
temperatures, and low generality.
3
5
dissociation enthalpy (107 kcal/mol), its weak acidity (pK =
We sought to design a system for room-temperature HCF
activation using neutral, weak LAs to avoid irreversible reactions
3
a
6
2
8) renders deprotonation strategies for C−H bond activation
tractable. Unlike CH , which can be readily transferred to
electrophilic substrates using organometallic reagents, analo-
2
,7
−
−
with bases and provide optimal stabilization of CF
.
3
3
8
Importantly, we hypothesized that a precisely tuned LA could
−
be recyclable, impart high CF3 nucleophilicity to a LA−CF
gous LiCF and MgX(CF ) are unstable because they irreversibly
3
3
3
9
−
adduct, and prevent F− elimination from CF3 at room
−
−
eliminate F , even at −80 °C. However, CF can be stabilized
3
through the formation of a Lewis acid (LA)−CF adduct; this
temperature. This represents a distinct concept in HCF3
activation: no systematic approach for the selection of Lewis
acids capable of providing these three desirable properties has
been reported.
We targeted alkali metal hydride derived bases (NaH, $0.10/
3
strategy forms the basis of all nucleophilic trifluoromethylation
1
0
reagents. The key challenge that limits the synthesis of LA−
−
CF3 reagents from HCF is poor compatibility between
3
components of the reaction mixture. The LA and Brønsted
mol; KH, $35/mol) for HCF deprotonation, and boron based
base must coexist in solution prior to HCF addition because the
3
3
−
LAs. A widely used solvent, dimethyl sulfoxide (DMSO), reacts
CF3 anion is extremely unstable. Furthermore, the base must
−
15
with alkali hydrides to produce KCH (SO)CH3 (pK = 35).
not irreversibly react with the LA, and the LA must not promote
2
a
−
Because of the low expense of this strong, soluble base and its
ability to deprotonate HCF , we selected it as an ideal basic
CF3 defluorination (Figure 1).
Two primary strategies have emerged to provide compatible
3
16
partner. Boron-based LAs were targeted because they have a
pairs of LAs and bases: the use of steric bulk to separate reactive
1
7
11
wide range of Lewis acidities, and can be easily prepared.
Lewis acidic and basic centers, and the use of Lewis pairs with
12
An appropriate LA must react reversibly with KCH (SO)CH
mismatched strength to enable reversible adduct formation.
2
3
in order to enable HCF deprotonation, while subsequently
Recently, steric control has been used to activate HCF using a
3
3
mixture of bulky bases (potassium bis(trimethylsilyl)amide
1
3
14
(
KHMDS) or phosphazene superbases) and LAs such as
Received: May 25, 2017
−
SiMe Cl. The instability of the CF intermediate (−80 °C)
3
3
©
XXXX American Chemical Society
A
DOI: 10.1021/jacs.7b05408
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
−
Figure 2. Development of LA−CF adducts from HCF . (a) LAs evaluated. (b) Calculated pK values of LAs (M062X/6-311++G(d,p)). (c) Yield of
3
3
CF3
−
LA−CF adduct from HCF . *: HCF was added to a 1:1 mixture of LA and KCH (SO)CH (0.1 M), and the yield of LA-CF was quantified by F-
3
3
3
2
3
3−
19
NMR spectroscopy.
−
providing sufficient Lewis acidity to capture and stabilize CF .
were observed (1, 2, and 3) in quantitative conversion within 5
3
To select LAs with a wide range of strengths for experimental
evaluation, the CF3 affinity of selected boron LAs was assessed
min at room temperature. These three LAs are easily obtained;
−
20
B(OMe) is a commodity chemical (<$1/mol), and B N Me
3
3
3
6
computationally using density functional theory (DFT). The ΔG
and (BOC H N) can be synthesized from simple starting
2 4 3
−
of the reaction between CF and a given LA was calculated at
materials (see SI for details).
3
18
Importantly, 2 is currently an expensive CF3− reagent with
reported applications in nucleophilic trifluoromethylation and
the M062X/6-311++G(d,p) level. The scale was set to zero
relative to the known adduct between dimethylformamide and
7
a
21
CF3, and the data were translated to provide predicted relative
copper-catalyzed cross-coupling. Solutions of 1 and 3 are
binding constants on a log scale (pKCF3) as a unified metric of
CF3 affinity. We used these data to select 13 LAs representing a
oxygen-stable, decompose on exposure to moisture, and return
the free borazine LAs upon thermal decomposition.
−
30 pKCF3 span for experimental evaluation in reactions between
To examine the mechanism of CF adduct formation, the
3
KCH (SO)CH , LAs, and HCF (Figure 2).
reaction between B N Me and KCH (SO)CH was followed
2
3
3
3
3
6
2
3
Equimolar quantities of KCH (SO)CH and each LA were
spectroscopically. The combination of equimolar KCH (SO)-
2
3
2
combined at room temperature in DMSO. HCF was added (1
CH and B N Me in DMSO afforded a homogeneous solution
3
3
3
3
6
19
atm), and the formation of B−CF adducts was assessed by F-
NMR spectroscopy. LAs with pK values above 11 exhibited
irreversible coordination to CH (SO)CH , and did not react
containing a single new species with C symmetry, as assessed by
3
s
1
13
11
CF3
NMR spectroscopy. H, C, and B-NMR spectra support the
formation of a 1:1 Lewis pair between KCH (SO)CH and
−
2
3
2
3
11
with HCF . LAs with pK values below 6 reacted with HCF ,
B N Me at room temperature (4). The B-NMR spectrum
3
CF3
3
3 3 6
−
but were insufficiently Lewis acidic to stabilize the CF anion
resulting from HCF deprotonation (Figure 2c).
exhibited a 2:1 set of resonances at +32.5 and −3.6 ppm. The
resonance at −3.6 ppm is consistent with a tetrahedral boron
3
19
3
Three LAs with intermediate pKCF3 values between 6 and 11
reacted with HCF to provide B−CF species in quantitative
center, whereas the broad resonance at 32.5 ppm (ν = 477 Hz)
1/2
3
3
is minimally shifted from the free B N Me (35.5), consistent
3
3
6
22
yield (Figure 3a). When either hexamethylborazine (B N Me ),
3
3
6
with two planar boron centers. The reversibility of KCH (SO)-
2
trimethyl borate (B(OMe) ), or trisethyleneoxyborazine
3
CH adduct formation with B N Me was examined by variable
3
3
3
6
1
(
(BOC H N) ) were combined with 1 equiv KCH (SO)CH ,
2 4 3 2 3
temperature NMR spectroscopy. At 15 °C, the H NMR
spectrum exhibited resonances at 0.04 and −0.44 ppm for the B-
followed by 1 equiv HCF in DMSO solvent, the B−CF adducts
3
3
CH resonances. As the temperature was raised, the resonances
3
broadened and coalesced at 35 °C; further increasing the
temperature to 90 °C resulted in the appearance of resonances
consistent with free B N Me (Figure S23). Upon cooling, 4 was
3
3
6
cleanly regenerated. The coalescence temperature of 35 °C was
‡
23
used to estimate a ΔG ≈ 14 kcal/mol. These data are
consistent with a dynamic exchange process between CH (SO)-
CH3 and B N Me at room temperature (Figure 3b).
2
−
3
3
6
The addition of 1 equiv HCF to 4 immediately (<1 min)
3
afforded 1 in 99% yield. NMR spectroscopy revealed a species
1
11
19
13
similar to 4, as assessed via H, B, F, and C NMR
2
spectroscopy. A new resonance at −65.7 ppm ( J
Hz) was observed in the F NMR spectrum, consistent with a
= 210
1
0B‑19F
19
B−CF adduct. Additionally, a new 2:1 set of resonances in the
3
11
B NMR spectrum at +33.1 and −5.7 ppm was observed along
Figure 3. (a) Synthesis of 1, 2, and 3 from HCF . (b) HCF activation by
3
3
1
13
with two 2:1 sets of −CH resonances in the H and C NMR
B N Me /base, ORTEP of 1. Ellipsoids shown at 50% probability; B1−
3
3
3
6
1
C2, 1.656(4) Å,; B1−C1, 1.627(4) Å; C1−B1−C2, 107.1(2). [K(18-
spectra, representing desymmetrized N−CH ( H: 2.49, 2.45
ppm. C: 34.73, 34.55 ppm.) and B-CH ( H: 0.08, −0.35 ppm.
3
+
13
1
crown-6)(THF)] omitted for clarity.
3
B
DOI: 10.1021/jacs.7b05408
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
1
3
C: 4.31, 0.16 ppm.) units. The sharp peaks exhibited by this
identical conditions; this implicates that 1 has a higher
nucleophilicity than 2 (Figure 4a).
1
13
19
complex in the H, C, and F NMR spectra suggest that
although 4 equilibrates with free KCH (SO)CH , the formation
The observation that B N Me can be released upon thermal
3 3 6
2
3
of 1 is irreversible at room temperature.
Preparation of 1 in the less polar solvent tetrahydrofuran
decomposition of 1 suggests that the free LA may be regenerated,
recovered, and reused after CF3− transfer. CO was selected as an
2
(
THF) required adjustments to the base and the countercation.
initial substrate to test this hypothesis. The addition of 4 atm
−
Potassium toluide (KTol) was selected as a base that can be
prepared on large scales and in high (>95%) yield from KOtBu,
BuLi, and toluene at 25 °C. The Lewis adduct between KTol,
1
spectroscopy and X-ray crystallography. 5 possesses similar
NMR spectra in comparison with 4: C symmetry and diagnostic
2
CO to 1 in DMSO afforded trifluoroacetate (CO CF ) in 93%
2
2
3
isolated yield (Figure 4b). B N Me was recovered in 95%
3 3 6
24
isolated yield by extraction into pentane; the recovery of the free
2
5
8-crown-6, and B N Me (5) was characterized using NMR
3 3 6
LA after CF transfer is a unique attribute of this system.
3
Transformations with high atom economy using 1 should be
2
9
10a
s
advantageous in comparison with SiMe CF /CsF,
KB-
3
3
:1 sets of B-CH and N−CH resonances. The solid state
16
3
3
(OMe )CF , or DMF/KOtBu/HCF , which generate stoi-
3
3
3
structure of 5 revealed a tetrahedral boron center, containing two
distinct B−C bond lengths for the B-CH and B-CH Ph bonds
chiometric waste (SiMe F) or require low temperatures (−80
3
3
2
°
C).
The high cost of trifluoromethylation reagents stems largely
(1.590(4) Å and 1.775(5) Å, respectively). The long B-CH Ph
2
2
6
bond length is consistent with a weak B−CH Ph bond. Similar
to 4, variable temperature H NMR spectra of 5 exhibited
dynamic behavior with broadening of the B−CH peaks at 25 °C,
which indicate reversible dissociation of the toluide base.
10a,30
2
from their multistep syntheses from CF Br or CF I.
The
1
3
3
regeneration of the B N Me LA in the reactions noted above
3
3
6
3
suggested that these popular reagents could be prepared from
HCF using B N Me as a recyclable component, thereby
3
3
3
6
Solutions of 1 were prepared in THF by the addition of 1 equiv
reducing the reaction inputs to base, HCF , and the direct
3
HCF to 5. 1 was obtained as a weighable solid in 95% yield, and
was structurally characterized by X-ray crystallography (Figure
3
3
precursor (Figure 5). Reagents used to install the CF group can
3
be divided between their use for CF , CF3·, and CF3+
−
31
32
3
b). The aromatic character of the borazine unit was disrupted by
33
transfer. The most important of these is SiMe CF , the
precursor to almost all other trifluoromethylation reagents.
3
3
the inclusion of a tetrahedral boron center with a new B−CF3
10a
bond (C1−B1−C2: 107.1(2)°), and elongation of the proximal
We used the preparation of this compound to demonstrate the in
situ recyclability of B N Me on a large scale.
B−N bond distances (B1−N1, 1.550(3) Å; B1−N2, 1.549(3) Å)
2
7
vs 1.44(3) in free borazine). The B1−C2 (CF ) bond
3
3
6
3
(
1.656(4) Å) is longer than the B1−C1 (CH ) bond (1.627(4)
3
Å), consistent with a weaker B−CF bond. DFT analyses
3
−
revealed a larger binding enthalpy of CH to B N Me than that
3
3
3
6
of CF3− by 8.5 kcal/mol (see SI). These structural and calculated
−
metrics indicate that CF transfer should be preferred over
CH3 transfer to electrophilic substrates.
3
−
Although KB(OMe) CF (2) has been previously shown to
3
3
−
facilitate nucleophilic CF3 transfer reactions, these proceed only
28
under forcing reaction conditions. Because nucleophilic CF3−
transfer necessitates the cleavage of a B−CF bond, we
3
−
hypothesized that CF reagents stabilized by weaker LAs may
3
exhibit superior nucleophilicity. 1 has a pKCF3 value 3.2 units
lower than 2, indicating that B N Me is a weaker LA than
3
3
6
B(OMe) . The addition of B(OMe) to 1 afforded 2 in 80%
3
3
yield, which is consistent with the difference in the calculated
−
CF3 affinity of B N Me and B(OMe) (Figure 4b). When 1
3
3
6
3
was allowed to react with benzophenone, the corresponding
trifluoromethylcarbinol was generated in 72% yield in 30 min at
room temperature. In contrast, 2 provided only 2% yield under
Figure 4. (a) Relative reactivity of 1 and 2 in nucleophilic
Figure 5. (a) Synthesis of SiMe CF , KSO CF , and Togni I from
3 3 2 3
−
19
trifluoromethylation of benzophenone. (b) CF3 transfer between 1
HCF . *: yield measured in situ by F-NMR spectroscopy. (b) Iterative
3
−
and B(OMe) ; synthesis of CF CO from HCF and subsequent
synthesis of SiMe CF with in situ B N Me recycling; NaCH (SO)-
3
3
2
3
3
3
3
3
6
2
recovery of B N Me .
CH made ex situ.
3
3
3
6
C
DOI: 10.1021/jacs.7b05408
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
Through ten cycles of an iterative addition/distillation
(5) Amphlett, J. C.; Coomber, J. W.; Whittle, E. J. Phys. Chem. 1966, 70,
5
93.
protocol, we achieved ∼5 turnovers with respect to B N Me
3
3
6
(6) Symons, E. A.; Clermont, M. J. J. Am. Chem. Soc. 1981, 103, 3127.
to obtain 34 mmol SiMe CF after distillation without the need
3
3
(
7) (a) Russell, J.; Roques, N. Tetrahedron 1998, 54, 13771.
for separation or purification of the borazine LA. The only
(
b) Zanardi, A.; Novikov, M. A.; Martin, E.; Benet-Buchholz, J.;
Grushin, V. V. J. Am. Chem. Soc. 2011, 133, 20901.
8) Grignard, V. Compt. rend 1900, 130, 1322.
(9) (a) Lishchynskyi, A.; Miloserdov, F. M.; Martin, E.; Benet-
Buchholz, J.; Escudero-Adan, E. C.; Konovalov, A. I.; Grushin, V. V.
consumed reagents were NaH, SiMe Cl, and HCF . The radical
3
3
32
CF · reagent KSO CF was also prepared in 66% isolated yield
by treating SO with 1 (98% recovery of B N Me ). Finally, the
hypervalent iodonium-CF reagent Togni I, a widely used CF
3
2
3
(
2
3
3
6
3
3
+
3
3
́
reagent, was synthesized in 78% chemical yield and with 98%
regeneration of B N Me by treating the appropriate iodaoxole
Angew. Chem., Int. Ed. 2015, 54, 15289. (b) Prakash, G. K. S.; Wang, F.;
Zhang, Z.; Haiges, R.; Rahm, M.; Christe, K. O.; Mathew, T.; Olah, G. A.
Angew. Chem., Int. Ed. 2014, 53, 11575.
3
3
6
with 1. We expect that direct access to these well-established
(
10) (a) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683.
b) Langlois, B. R.; Billard, T.; Roussel, S. J. Fluorine Chem. 2005, 126,
73.
11) (a) Stephan, D. W. J. Am. Chem. Soc. 2015, 137, 10018. (b) Ero
G.; Nagy, K.; Mehdi, H.; Papai, I.; Nagy, P.; Kiraly, P.; Tarkanyi, G.;
Soos, T. Chem. - Eur. J. 2012, 18, 574. (c) Stephan, D. W.; Erker, G.
Angew. Chem., Int. Ed. 2015, 54, 6400.
12) (a) Mahdi, T.; Stephan, D. W. J. Am. Chem. Soc. 2014, 136, 15809.
nucleophilic, radical, and electrophilic reagents from HCF may
3
(
increase access to the CF group in existing large-scale processes.
3
1
In summary, we have developed a predictive design concept
that led to the preparation of several trifluoromethylation
(
̋
s,
́
́
́
́
reagents from HCF . One of these, 1, exhibited high
3
́
−
nucleophilicity at room temperature. After CF3 transfer, the
free LA was quantitatively regenerated. We exploited this
property to present an iterative synthesis of SiMe CF on a
(
3
3
(b) Scott, D. J.; Fuchter, M. J.; Ashley, A. E. J. Am. Chem. Soc. 2014, 136,
large scale from NaH, HCF , and SiMe Cl as the only consumed
15813.
3
3
reagents with repeated in situ reuse of the LA. This methodology
provides direct access to other common trifluoromethylating
reagents from HCF , including K(B(OMe) CF , KSO CF ,
(13) Prakash, G. K. S.; Jog, P. V.; Batamack, P. T. D.; Olah, G. A. Science
2
(
2
(
012, 338, 1324.
14) Kawai, H.; Yuan, Z.; Tokunaga, E.; Shibata, N. Org. Biomol. Chem.
013, 11, 1446.
15) Brown, C. A. J. Org. Chem. 1974, 39, 3913.
16) Folleas, B.; Marek, I.; Normant, J.-F.; Jalmes, L. S. Tetrahedron
3
3
3
2
3
KCO CF , and Togni reagent I. Finally, we introduce borazines
2
3
as a class of tunable, weak LAs for synthetic applications. The
rational selection of compatible LAs and bases for efficient
(
́
Lett. 1998, 39, 2973.
nucleophilic trifluoromethylation using HCF is a design strategy
3
(17) Sivaev, I. B.; Bregadze, V. I. Coord. Chem. Rev. 2014, 270−271, 75.
that may also be applied to other unstable anions to promote
other difficult nucleophilic functionalizations.
(18) (a) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215.
(b) Rassolov, V. A.; Ratner, M. A.; Pople, J. A.; Redfern, P. C.; Curtiss, L.
A. J. Comput. Chem. 2001, 22, 976.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.7b05408.
(19) See SI for details.
■
(20) Banfi, L.; Narisano, E.; Riva, R.; Matteson, D. S. In Encyclopedia of
*
S
Reagents for Organic Synthesis; Paquette, L. A., Ed.; John Wiley & Sons,
Ltd, 2001.
(
21) Knauber, T.; Arikan, F.; Ro
Chem. - Eur. J. 2011, 17, 2689.
22) Kennedy, J. D. In Multinuclear NMR; Mason, J., Ed.; Springer,
987; p 221.
23) Jackman, L. Dynamic nuclear magnetic resonance spectroscopy;
Elsevier, 2012.
̈
schenthaler, G.-V.; Gooßen, L. J.
Crystallographic information for 1 and 5 (CIF)
Synthetic details, characterization (PDF)
(
1
(
AUTHOR INFORMATION
Corresponding Author
nszym@umich.edu
■
*
(24) Lochmann, L.; Trekoval, J. J. Organomet. Chem. 1987, 326, 1.
(25) 18-crown-6 was added to improve the stability of 1 in THF, due to
−
the previously observed sensitivity of CF3 species toward alkali metal
cations. See reference 13.
ORCID
(
26) Cambridge crystallographic database search (CSD version 5.38,
updated November 2016).
̈
27) Dearomatized borazines: (a) Noth, H.; Troll, A. Eur. J. Inorg.
Nathaniel K. Szymczak: 0000-0002-1296-1445
Notes
(
The authors declare the following competing financial
interest(s): We have a patent pending on content relating to
this manuscript.
Chem. 2005, 2005, 3524. (b) Carter, T. J.; Kampf, J. W.; Szymczak, N. K.
Angew. Chem., Int. Ed. 2012, 51, 13168. (b1) Carter, T. J.; Wang, J. Y.;
Szymczak, N. K. Organometallics 2014, 33, 1540−1543.
(28) Levin, V. V.; Dilman, A. D.; Belyakov, P. A.; Struchkova, M. I.;
ACKNOWLEDGMENTS
Tartakovsky, V. A. Tetrahedron Lett. 2011, 52, 281.
■
(
(
29) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
30) Burton, D. J.; Qui, W.; Sanchez-Rosello, M.; del Pozo Losada, C.;
a, J. In Encyclopedia of Reagents for Organic Synthesis; Paquette,
This work was supported by the NSF-CAREER program (grant
CHE-1350877), a Rackham Graduate Student Research Grant
J.B.G.) and the NSF (Grant CHE-0840456) for X-ray
instrumentation. N.K.S. is a Camille Dreyfus Teacher-Scholar
and an Alfred P. Sloan Research Fellow. We thank Dr. Jeff Kampf
for crystallographic assistance.
́
́
Luis Acen
̃
(
L. A., Ed.; John Wiley & Sons, Ltd, 2001.
(31) Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S. J. Org. Chem.
1991, 56, 984.
(32) Zhang, C. Adv. Synth. Catal. 2014, 356, 2895.
(
33) Charpentier, J.; Fru
̈
h, N.; Togni, A. Chem. Rev. 2015, 115, 650.
REFERENCES
■
(
1) Wishart, D. S.; Knox, C.; Guo, A. C.; Shrivastava, S.; Hassanali, M.;
Stothard, P.; Chang, Z.; Woolsey, J. Nucleic Acids Res. 2006, 34, D668.
(
(
(
2) Grushin, V. V. Chim. Oggi 2014, 32, 81.
3) McCulloch, A.; Lindley, A. A. Atmos. Environ. 2007, 41, 1560.
4) Olsbye, U. Angew. Chem., Int. Ed. 2016, 55, 7294.
D
DOI: 10.1021/jacs.7b05408
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX