"naked" Lithium Cation: Strongly Activated Metal Cations Facilitated by Carborane Anions

Article abstract of DOI:10.1021/acs.joc.6b02677

Experimental and spectroscopic studies revealed unprecedented reactivity of a "naked" lithium cation with very weakly coordinating anions, including carborane anions. The superactivated lithium cation has greatly enhanced Lewis acidic character and mediates various organic reactions such as carbonyl-ene reaction, NBS-bromination of unactivated aromatics, and Friedel-Crafts alkylation, which are not promoted by conventional lithium salts. Chemical robustness of the counteranion also plays an important role in the chemistry of the strongly activated lithium cation.

Full text of DOI:10.1021/acs.joc.6b02677

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Article
“Naked” Lithium Cation: Strongly Activated
Metal Cations Facilitated by Carborane Anions
Yu Kitazawa, Ryo Takita, Kengo Yoshida, Atsuya Muranaka, Seijiro Matsubara, and Masanobu Uchiyama
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02677 • Publication Date (Web): 19 Jan 2017
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“Naked” Lithium Cation:
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Strongly Activated Metal Cations Facilitated by Carborane Anions
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Yu Kitazawa,† Ryo Takita,*, ‡ Kengo Yoshida,‡ Atsuya Muranaka,‡ Seijiro Matsubara,§ Masanobu
Uchiyama*,
†, ‡
† Graduate School of Pharmaceutical Sciences, The University of Tokyo
7ꢀ3ꢀ1 Hongo, Bunkyoꢀku, Tokyo 113ꢀ0033, Japan
‡ Elements Chemistry Laboratory, RIKEN, and Advanced Elements Chemistry Research Team, RIKEN Center
for Sustainable Resource Science (CSRS)
2ꢀ1 Hirosawa, Wakoꢀshi, Saitama 351ꢀ0198, Japan
§ Department of Material Chemistry, Graduate School of Engineering
Kyoto University
KyotodaigakuꢀKatsura, Nishikyo, Kyoto 615ꢀ8510 (Japan)
TOC Graphic
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Abstract
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Experimental and spectroscopic studies revealed unprecedented reactivity of “naked” lithium
cation with very weakly coordinating anions including carborane anions. The superꢀactivated
lithium cation has greatly enhanced Lewis acidic character, and mediates various organic
reactions, such as carbonylꢀene reaction, NBSꢀbromination of unactivated aromatics, and
FriedelꢀCrafts alkylation, that are not promoted by conventional lithium salts. Chemical
robustness of the counter anion also plays an important role in the chemistry of strongly
activated lithium cation.
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INTRODUCTION
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Hydrogen and lithium are vertically adjacent elements in the periodic table, and are categorized
as congeneric elements. However, they differ in many respects, including electronegativity (H
2.2 vs Li 1.0). This dissimilarity is reflected in their acid chemistry: for instance,
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–
trifluoromethanesulfonic acid (CF3SO3H: TfO–H+) and fluorosulfonic acid (FSO3 H+) have been
traditionally employed as superacids (super Brønsted acids), enabling a range of superacidꢀ
promoted synthetic transformations,1 whereas Li+OTf– and Li+OSO2F– are essentially ineffective
in most of these reactions because the potent electropositivity of lithium cation prevents
complete dissociation of the counter anion. Indeed, the chemistry of “naked” metal cations (i.e.,
super-activation of metal cations) has not been well developed in general. Given that a wide
variety of elements can be used in Lewis acid/metal cation chemistry, the development of superꢀ
activated metal cations should open up tremendous possibilities for enhanced or unprecedented
reactivity. Here, we report a systematic study designed to generate “naked” Li+. The key to
success proved to be appropriate design/choice of counter anions. The formation of superꢀ
activated Li+ was confirmed by 7Li NMR and UVꢀvis spectroscopies. We found that superꢀ
activated lithium cation, which has greatly enhanced Lewis acidic character, mediates various
reactions, such as carbonylꢀene reaction, NBSꢀbromination of unactivated aromatics, and
FriedelꢀCrafts alkylation, that are not promoted by “conventional” lithium salts.
RESULTS AND DISCUSSION
To screen suitable counter anions to maximize the intrinsic character of Li+, we systematically
examined various anions, including traditional weakly coordinating anions (WCAs: OTf–, NTf2 ,
–
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–
–
–
BF4 and ClO4 ),2 borateꢀbased anions (BARF– and TFPB–),3,4 and carborane anions (CB11H12
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4
5
6
7
8
– 5
and CB11H6Br6 ) (Figure 1). Carborane anion is an icosahedral cluster molecule composed of 1
carbon and 11 boron atoms with exceptionally low basicity/nucleophilicity.6 In addition, it can be
flexibly functionalized,5b,7 enabling precise tuning of its characteristics.
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Borate Anions
WCAs
NTf2
CF3
F
F
OTf
BF4
B
B
F
CF3
F
F
4
4
ClO4
BARF–
TFPB–
Carborane Anions
Br
Br
Br
Br
Br
Br
: carbon vertex
–
–
CB11H12
CB11H6Br6
Figure 1. Counter Anions Investigated in This Work with Weak Coordinating Ability
Table 1. 7Li NMR Data of the Lithium Salts a
a All spectra were recorded in liquid SO2 at –20°C and referenced to external LiCl in acetoneꢀd6
(see Supporting Information for details). b These ꢁδ (7Li) values were not determined because
LiBF4 and LiClO4 were only sparingly soluble in liquid SO2.
Firstly, we measured the 7Li NMR spectra of the lithium salts in liquid SO2 as a solvent8 (Table
1). Although Brønsted acidity can be easily assessed using parameters such as acid dissociation
constant (pKa) and Hammett acidity function (H0), evaluation of the Lewis acidity of metal
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cations is difficult due to the lack of a similar index. The 7Li signals of Li+OTf– and Li+NTf2
were observed as a sharp singlet at –1.56 and –1.50 ppm, respectively, under the conditions
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given in Table 1 (entries 1 and 2), while signals of Li+BF4 and Li+ClO4 could not be recorded
because these salts did not dissolve under the NMR conditions. On the other hand, lithium salts
of borate and carborane anions showed lowerꢀfield shifts to the observation limit (ca. –1.28
ppm),9 which indicates that they have lower electron density (entries 5ꢀ8).
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Table 2. Effects of Counter Anions on the Lewis Acidity of Lithium Cation in Trityl Cation (2)
Formation
λ
max = 410 nm
Li salt (1 equiv)
CH2Cl2, r.t.
Abs
OH
Ph
Ph
Ph
Ph
X
Ph
Ph
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2
Abs
= 410 nm)
Entry Li salt
Entry Li salt
(
λ
= 410 nm)
(
λ
ND
ND
ND
ND
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LiOTf
LiNTf2
LiBF4
LiClO4
LiTFPB
LiBARF
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4
1.14
0.28a
0.16a
1.24
LiCB11H12
LiCB11H6Br6
a Decrease of the peak intensity at 410 nm was observed during the course of measurement.
We then performed a UVꢀvis spectral study to evaluate the generation of trityl cation (2) (at 410
nm) via Lewis acidic activation of trityl alcohol (1), as reported by Kobayashi and coꢀworkers.10
The lithium salts of borate and carborane anions, Li+TFPB–, Li+BARF–, Li+CB11H12 , and
–
Li+CB11H6Br6 , were sufficiently reactive to generate 2 (Table 2, entries 5ꢀ8), whereas Li+OTf–,
–
Li+NTf2 , Li+BF4 , and Li+ClO4 produced no spectral change (entries 1ꢀ4). This indicates that
–
–
–
there is a distinct difference of Lewis/metal acidity between them, which is in accordance with
the 7Li NMR results. Note that in the cases of Li+BARF– and Li+CB11H12 , the absorbance of 2
–
diminished during the course of measurements, implying that side reactions or decomposition of
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2 occur in the presence of these counter anions.11 These results suggest that not only counter
anion stability (i.e., extremely low nucleophilicity), but also chemical robustness, that is,
tolerance to side reactions/decomposition, would be necessary to enable superꢀactivation of the
Li+ center.
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Table 3. CarbonylꢀEne Reaction of Citronellal (3)
a Yields were determined by GC analysis using tridecane as an internal standard.
With the spectroscopic results in hand, we next examined whether superꢀactivated lithium could
promote various fundamental reactions that do not proceed in the presence of ordinary lithium
salts. Carbonyl activation is a key step for organic transformation. For example, carbonylꢀene
reaction generally requires strong Lewis acids to activate the carbonyl group.12 When Li+OTf–,
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Li+NTf2 , Li+BF4 , or Li+ClO4 was employed for the carbonylꢀene reaction of citronellal (3) in
dichloromethane at 0°C, the desired product 4 was not obtained at all and only the starting 3 was
recovered (Table 3, entries 1ꢀ4). In contrast, the desired cyclization proceeded under the same
conditions in the presence of a catalytic amount of Li+TFPB–, Li+BARF–, Li+CB11H12 , or
–
Li+CB11H6Br6 (entries 5ꢀ8).
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Table 4. Bromination of Benzene (6) with NBS (5)
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a Yields were determined by GC analysis using tridecane as an internal standard.
Inspired by the success of the first carbonylꢀene reaction catalyzed by lithium salts (i.e.,
intramolecular C–C bond formation via carbonyl activation), we then examined the bromination
of benzene (6) by activation of Nꢀbromosuccinimide (NBS) (5) (Table 4). With nonꢀactivated
benzenes, this reaction requires superꢀelectrophilic reagents, such as (multiply) protonated NBS
–
–
reagents in superacid.13 Again, ordinary lithium salts such as Li+OTf–, Li+NTf2 , Li+BF4 , or
–
Li+ClO4 did not mediate the bromination reaction at all (entries 1ꢀ4). On the other hand, the
–
combination of NBS with 1 equivalent of Li+CB11H6Br6 successfully brominated benzene (7) in
84% yield at 100°C for 24 h (entry 8). Moreover, even bromobenzene (7), a deactivated benzene
substrate, could be brominated in the presence of 1.5 equivalents of Li+CB11H6Br6 to give the
–
–
product 8 in 50% yield (eq. 1). With Li+TFPB–, Li+BARF–, or Li+CB11H12 , the reaction was
sluggish and bromination of carborane anion or decomposition of the borate scaffold occurred
preferentially (entries 5ꢀ7).14 These results indicate that the reaction requires 1) an extremely
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acidic lithium cation that strongly activates NBS to give superꢀelectrophilic brominating
reagents, and 2) a robust anion skeleton compatible with the generated superꢀelectrophilic
species.
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Table 5. FriedelꢀCrafts Alkylation of Benzene (6) with Benzyl Alcohol (9)
a Yields were determined by GC analysis using tridecane as an internal standard
Intermolecular FriedelꢀCrafts (FC) alkylation reaction of benzene was next investigated (Table
5). For the success of FC reactions using alcohols (OH is a poor leaving group) as the
electrophile, the use of superacid or strong Lewis acid is generally required.15 Indeed, no reaction
of 9 took place in the presence of Li+OTf–, Li+NTf2 , Li+BF4 , or Li+ClO4 . However, we found
–
–
–
–
that the use of Li+TFPB– or Li+CB11H6Br6 gave the desired FC product 10 in 95% or 94% yield,
respectively (entries 5 and 8). On the other hand, decomposition/side reactions of the anion
moiety prior to the FC reaction were observed when Li+BARF– or Li+CB11H12– was employed.
Table 6. Intramolecular Cyclization of 2ꢀPhenylethynylaniline (11) to Afford 2ꢀPhenylindole
(12)
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a Yields were determined by GC analysis using tridecane as an internal standard
Finally, to characterize the behavior of lithium cation compared with normal superacids such as
TfO–H+, we focused on activation of a lessꢀpolar alkyne triple bond. Indole synthesis from oꢀ
alkynylanilines (Table 6) was selected because “soft” metals are generally required to activate
the C–C π bond,16 and superacids are ineffective for the annulation, presumably due to
preferential protonation of the aniline nitrogen in superacid media.[17] When ordinary lithium
salt, Li+OTf–, Li+NTf2 , Li+BF4 , or Li+ClO4 , was employed, the desired indole annulation
proceeded, albeit in low yield, probably due to the low acidity (entries 1ꢀ4). In sharp contrast, the
use of Li+CB11H12– promoted the desired annulation reaction to give 12 in 84% yield. Other
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–
–
lithium salts with borate anions and Li+CB11H6Br6 seemed to favor strong coordination to
nitrogen, which disturbed the indole cyclization.
In summary, combined spectroscopic and experimental studies demonstrated that the Lewis
acidity and character of lithium cation can be finelyꢀtuned by means of an appropriate choice of
counter anion. In particular, carborane anions strongly activated lithium cation to achieve
unprecedented reactivity, and the superꢀactivated lithium cation mediated various reactions
(carbonylꢀene reaction, NBSꢀbromination of unactivated aromatics, FriedelꢀCrafts alkylation)
that are not promoted by conventional lithium salts. Counter anion stability and chemical
robustness are both crucial to prevent side reactions. Given that the carborane anion is readily
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customizable,5b including carboraneꢀbased multivalent anions,7a we anticipate that carborane
anions will be an excellent platform for the flexible design of super-activated metal centers in
periodic table-wide chemistry. We believe the concept/methods described herein offer a toolkit
that will be of general use for exploration of a range of superꢀactivated metal cations.
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Experimental Section
General Remarks
Me3NHCB11H12 and CsCB11H12 were purchased from commercial suppliers. Bromobenzene,
citronellal, Nꢀbromosuccinimide, and benzyl alcohol were used after appropriate purification
(distillation or recrystallization). 2ꢀPhenylethynylaniline was prepared as described previously.18
Lithium Tetrakis(3,5ꢀtrifluoromethyl)phenylborate, LiBARF. was prepared as described
previously.19 Lithium trifluoromethanesulfonate, lithium bis(trifluoromethanesulfonimide),
lithium tetrafluoroborate, and lithium perchlorate were used after drying under vacuum (1.0 ×
10–1 hPa/80ºC overnight). All other chemicals were of reagent grade and used as received. Airꢀ
and moistureꢀsensitive manipulations were performed with standard Schlenk techniques or in a
glove box under argon atmosphere. Normalꢀphase column chromatography was performed with
silica gel 60 (230ꢀ400 mesh) and thinꢀlayer chromatography was carried out on 0.25 mm silica
gel plates. The NMR spectral measurements were performed on a 500 MHz spectrometer.
Chemical shifts are expressed in
δ (ppm) values, and coupling constants are expressed in hertz
1
(Hz). H, 13C NMR spectra were referenced to tetramethylsilane as an internal standard. The
following abbreviations are used: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet,
and bs = broad singlet.
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Synthesis of Trimethylammonium 7,8,9,10,11,12-hexabromo-1-carba-closo-dodecaborate,
(NMe3H)CB11H6Br6. [442549-75-9]
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CsCB11H6Br6 (2.5 g, 3.35 mmol) was dissolved in an aqueous solution of HCl (10%, 100 mL)
and extracted with Et2O three times. The combined Et2O extracts were evaporated to dryness.
The solid residue was treated with water. The product was precipitated by addition of NHMe3Cl
(960 mg, 10.05 mmol). The white solid was filtered off, washed with water, and dried under
vacuum (1.0 × 10–1 hPa/100ºC, overnight) to give the title compound as white powder in 85%
yield (1900 mg). This compound was previously reported.[20a, b] 1H{11B} NMR (500 MHz,
acetoneꢀd6): 2.33 (bs, 5H), 3.04 (bs, 1H), 3.23 (s, 9H); HRMS (ESIꢀTOF) m/z calcd. for
CH6B11Br6 ([M]–): 616.6605, found: 616.6601.
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Synthesis of Lithium 7,8,9,10,11,12-hexabromo-1-carba-closo-dodecaborate, LiCB11H6Br6.
[225797-12-6]
Typical Procedure A: To the aqueous solution (200 mL) of (NMe3H)CB11H6Br6 (2.0 g, 2.97
mmol) was added LiOH•H2O (374 mg, 8.92 mmol). This solution was stirred for 60 min at room
temperature and then evaporated to dryness. The solid was treated with water again and extracted
with Et2O three times. The Et2O fractions were washed with an aqueous solution of LiOH (10%),
LiCl (20%), and water, and then dried with activated molecular sieves (powdered, 4 Å). The
sieves were filtered off and washed with dry Et2O. The combined Et2O extracts were stirred with
LiH (1.0 g) for 24 h under an argon atmosphere at room temperature, filtered to remove any
residual LiOH and LiH, and evaporated under reduced pressure to afford brown oil. The oil was
dissolved in acetonitrile (100 mL) and the solution was stirred overnight with activated charcoal
(200 mg). The charcoal was filtered off through Celite® pad and washed with acetonitrile.
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Combined filtrates were evaporated, and the product was dried under reduced pressure (1.0 × 10–
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hPa/130ºC, 7 days) to give the title compound as white powder in 68% yield (1958 mg). This
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compound was previously reported.21 1H{11B} NMR (500 MHz, acetoneꢀd6): 2.33 (bs, 5H), 3.03
(bs, 1H); HRMS (ESIꢀTOF) m/z calcd. for CH6B11Br6 ([M]–): 616.6605, found: 616.6604.
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Synthesis of Lithium 1-carba-closo-dodecaborate, LiCB11H12. [92468-37-6]
According to the Typical Procedure A, using NMe3HCB11H12 (2.0 g, 9.84 mmol) and LiOH•H2O
(4958 mg, 29.5 mmol), the titled compound was obtained as white powder in 74% yield (1092
mg). This compound was previously reported.22 1H{11B} NMR (500 MHz, acetoneꢀd6): 1.57 (bs,
5H), 1.66 (bs, 5H), 1.73 (bs, 1H), 2.23 (bs, 1H); HRMS (ESIꢀTOF) m/z calcd. for CH12B11 ([M]–
): 143.2035, found: 143.2038.
General Procedure for Carbonyl-Ene Reaction of Citronellal (3)
LiCB11H6Br6 (13.7 mg, 0.022 mmol) and dichloromethane (5.0 mL) were charged in a dried
Schlenk tube in a glove box. To the mixture was added citronellal (17.1 mg, 0.11 mmol). The
mixture was stirred at 0ºC for 24 h, and then the reaction was quenched by brine. The generation
1
of the desired compound (4: mixture of two isomer) (69%) was confirmed by comparison of H
NMR spectrum and GC/MS trace of the authentic sample.12d Chemical yield was determined by
GC analysis using tridecane as an internal standard.
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Major isomer of 4: Isopulegol [7786-67-6]. H NMR data are consistent with those previously
reported.12d
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General Procedure for Bromination of Benzene (6) with NBS (5)
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Benzene (3.0 mL), LiCB11H6Br6 (62.3 mg, 0.1 mmol), and Nꢀbromosuccinimide (5, 17.2 mg, 0.1
mmol) were charged in a dried Schlenk tube in a glove box. The mixture was stirred at 100ºC for
24 h in the dark, and the reaction was quenched by brine. The generation of the desired
compound 7 (84%) was confirmed by comparison of 1H NMR spectrum and GC/MS trace of the
commercially available authentic sample. Chemical yield was determined by GC analysis using
tridecane as an internal standard.
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Bromobenzene (7): [7786-67-6]. H NMR data are consistent with a commercially available
authentic sample.
Major isomer of 8: 1,4-Dibromobenzene [106-37-6]. 1,4ꢀDibromobenzene (47%) was obtained
by using LiCB11H6Br6, NBS (5), and bromobenzene (7) at 150ºC. Chemical yield was
1
determined by GC analysis using tridecane as an internal standard. H NMR data are consistent
with commercially available authentic sample.
General Procedure for Friedel-Crafts Alkylation
Benzene (1.0 mL) and LiCB11H6Br6 (12.0 mg, 0.02 mmol) were charged in a dried Schlenk tube
in a glove box. To the mixture was added benzyl alcohol (9, 10.4 mg, 0.1 mmol). The mixture
was stirred at 100ºC for 24 h, then the reaction was quenched by brine. The generation of the
1
desired compound 10 (94%) was confirmed by comparison of H NMR spectrum and GC/MS
trace of the authentic sample.23 Chemical yield was determined by GC analysis using tridecane
as an internal standard.
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1,1-Diphenylmethane (10): [612-00-0]. H NMR data are consistent with commercially
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available authentic sample.23
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General Procedure for Indole Cyclization of 2-Phenylethynylaniline (11)
Toluene (27 mL), LiCB11H6Br6 (19.3 mg, 0.031 mmol), and 2ꢀphenylethynylaniline (11, 30 mg,
0.155 mmol) were charged in a dried Schlenk tube in a glove box. The mixture was stirred at
120ºC for 24 h, and the reaction was quenched by brine. The generation of the desired compound
12 (50%) was confirmed by comparison of 1H NMR spectrum and GC/MS trace of the authentic
sample.24 Chemical yield was determined by GC analysis using tridecane as an internal standard.
1
2-Phenyl-1H-indole (13): [948-65-2]. H NMR data are consistent with those previously
reported.24
Associated Content
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
10.1021/acs.joc.xxxxxxx.
7
1
UVꢀvis absorption spectra, representative Li NMR spectra, and copies of H NMR spectra of
known compounds for purity.
Author Information
Corresponding Authors
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*Eꢀmail: ryo.takita@riken.jp
*Eꢀmail: uchi_yama@riken.jp
Notes
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The authors declare no competing financial interest.
Acknowledgements
This work was supported by JSPS KAKENHI (S) (No. 24229011), The Asahi Glass Foundation,
Foundation NAGASE Science Technology Development, and Sumitomo Foundation (to M. U.)
and JSPS GrantꢀinꢀAid for Young Scientists (A) (No. 25713001) (to R. T.). Y. K. thanks RIKEN
Junior Research Associate program (until March 2015) and the JSPS Research Fellowship for
Young Scientists (from April 2015).
References
(1) (a) Olah, G. A.; Prakash, G. K. S.; Molnar, A.; Sommer, J. Superacid chemistry, 2nd ed.;
Wiley: Hoboken, N. J., 2009. (b) Olah, G. A. Carbocations and electrophilic reactions; Wileyꢀ
VCH: Weinheim, 1974.
(2) For the reviews of WCAs, see: (a) Beck, W.; Sünkel, K. Chem. Rev. 1988, 88, 1405. (b)
Bochmann, M. Angew. Chem. Int. Ed. Engl. 1992, 31, 1181. (c) Strauss, S. H. Chem. Rev. 1993,
93, 927. (d) Krossing, I.; Raabe, I. Angew. Chem. Int. Ed. 2004, 43, 2066. (e) Antoniotti, S.;
Dalla, V.; Duñach, E. Angew. Chem. Int. Ed. 2010, 49, 7860. (f) Engesser, T. A.; Lichtenthaler,
M. R.; Schleep, M.; Krossing, I. Chem. Soc. Rev. 2016, 45, 789.
(3) (a) Nishida, H.; Takada, N.; Yoshimura, M.; Sonoda, T.; Kobayashi, H. Bull. Chem. Soc. Jpn.
1984, 57, 2600. For the representative examples of Li+TFPB–, see: (b) Golden, J. H.; Mutolo, P.
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Page 16 of 19
1
2
3
4
5
6
7
8
9
F.; Lobkovsky, E. B.; DiSalvo, F. J. Inorg. Chem. 1994, 33, 5374. (c) Fujiki, K.; Ikeda, S.;
Kobayashi, H.; Mori, A.; Nagira, A.; Nie, J.; Sonoda, T.; Yagupolskii, Y. Chem. Lett. 2000, 29,
62.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(4) (a) Massey, A. G.; Park, A. J. J. Organomet. Chem. 1964, 2, 245. For the representative
examples of Li+BARF–, see: (b) Nakano, M.; Matsuo, J.; Mukaiyama, T. Chem. Lett. 2000, 29,
1010. (c) Mukaiyama, T.; Nakano, M.; Kikuchi, W.; Matsuo, J. Chem. Lett. 2000, 29, 1352. (d)
Uyanik, M.; Nakashima, D.; Ishihara, K. Angew. Chem. Int. Ed. 2012, 51, 9093.
(5) (a) Körbe, S.; Schreiber, P. J.; Michl, J. Chem. Rev. 2006, 106, 5208. (b) Douvris, C.; Michl,
J. Chem. Rev. 2013, 113, PR179. Michl and coꢀworkers reported the elegant use of lithium–
carboranes in the olefin polymerization and some rearrangement reactions, see: (c) Moss, S.;
King, B. T.; de Meijere, A.; Kozhushkov, S. I.; Eaton, P. E.; Michl, J. Org. Lett. 2001, 3, 2375.
(d) Vyakaranam, K.; Barbour, J. B.; Michl, J. J. Am. Chem. Soc. 2006, 128, 5610. (e) Clark, T. J.
Am. Chem. Soc. 2006, 128, 11278. (f) Volkis, V.; Douvris, C.; Michl, J. J. Am. Chem. Soc. 2011,
133, 7801. (g) Merna, J.; Vlček, P.; Volkis, V.; Michl, J. Chem. Rev. 2016, 116, 771.
(6) For recent examples of isolation/utilization of unstable cationic species and preparation of the
strongest Brønsted acid, see: (a) Douvris, C.; Ozerov, O. V. Science 2008, 321, 1188. (b) Reed,
C. A. Acc. Chem. Res. 2010, 43, 121. (c) RamírezꢀContreras, R.; Bhuvaneshi N.; Zhou, J.;
Ozerov, O. V. Angew. Chem. Int. Ed. 2013, 52, 10313. (d) Shoji, Y.; Tanaka, N.; Mikami, K.;
Uchiyama, M.; Fukushima, T. Nat. Chem. 2014, 6, 498. (e) Nava, M.; Stoyanova, I. V.;
Cummings, S.; Stoyanov, E. S.; Reed, C. A. Angew. Chem. Int. Ed. 2014, 53, 1131. See also ref.
5b.
(7) (a) Kanazawa, J.; Takita, R.; Jankowiak, A.; Fujii, S.; Kagechika, H.; Hashizume, D.; Shudo,
K.; Kaszyński, P.; Uchiyama, M. Angew. Chem. Int. Ed. 2013, 52, 8017. (b) Kitazawa, Y.;
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9
Otsuka, M.; Kanazawa, J.; Takita, R.; Uchiyama, M. Synlett 2015, 26, 2403. (c) Otsuka, M.;
Takita, R.; Kanazawa, J.; Miyamoto, K.; Muranaka, A.; Uchiyama, M. J Am. Chem. Soc. 2015,
137, 15082.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
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35
36
37
38
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45
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(8) Liquid SO2 has minimal basicity and provides relatively good solubility, as described in
connection with related NMR studies of carborane (Brønsted) acids, see: (a) Juhasz, M.;
Hoffmann, S.; Stoyanov, E.; Kim, K.ꢀC.; Reed, C. A. Angew. Chem. Int. Ed. 2004, 43, 5352. (b)
Reed, C. A. Chem. Commun. 2005, 16697.
(9) This limit is due to the leveling effects of liquid SO2. Similar phenomena were observed in
+
Ref. 8, where they were ascribed to diꢀsolvation (H(SO2)2 ), even though liquid SO2 has very
weak basicity.
(10) Ikeda, S.; Kobayashi, H.; Sonoda, T.; Nie, J.; Sonoda, A.; Yagupolskii, Y. A.; Mori, A.
Kyushu Univ. Int. Rep. 2001, 15, 101.
(11) Alkylated adducts of carborane anion by trityl cation 2 were observed in the ESIꢀMS
spectrum. Decomposition of BARF was indicated by the absence of the corresponding peak in
the ESIꢀMS spectrum.
(12) (a) Sakai, K.; Oda, O. Tetrahedron Lett. 1972, 13, 4375. (b) Nakatani, Y.; Kawashima, K.
Synthesis 1978, 1978, 147. (c) Aggarwal, V.; Vennall, G.; Davey, P.; Newman, C. Tetrahedron
Lett. 1998, 39, 1997. (d) Kočovský, P.; Ahmed, G.; Šrogl, J.; Malkov, A. V.; Steele, J. J. Org.
Chem. 1999, 64, 2765.
(13) For examples using superacid, see: (a) Lambert, F. L.; Ellis, W. D.; Parry, R. J. J. Org.
Chem. 1965, 30, 304. (b) Prakash, G. K. S.; Mathew, T.; Hoole, D.; Esteves, P. M.; Wang, Q.;
Rasul, G.; Olah, G. A. J. Am. Chem. Soc. 2004, 126, 15770. (c) Rajesh, K.; Somasundaram, M.;
Saiganesh, R.; Balasubramanian, K. K. J. Org. Chem. 2007, 72, 5867. For examples using metal
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5
6
7
8
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catalysts, see: (d) Tanemura, K.; Suzuki, T.; Nishida, Y.; Satsumabayashi, K.; Horaguchi, T.
Chem. Lett. 2003, 32, 932. (e) Mo, F.; Yan, J. M.; Qiu, D.; Li, F.; Zhang, Y.; Wang, J. Angew.
Chem. Int. Ed. 2010, 49, 2028.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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(14) Oligoꢀbrominations (monoꢀ to hexaꢀbromination) of carborane anion were observed (ESIꢀ
MS analysis). In the cases of TFPB and BARF, decomposition was observed to give C6F5Br and
3,5ꢀ(CF3)2C6H3Br, respectively (EIꢀMS analysis).
(15) (a) Roberts, R. M.; Khalaf, A. Friedel-Crafts alkylation chemistry: a century of discovery;
M. Dekker: New York, 1984. (b) Rueping, M.; Nachtsheim, B. J.; Ieawsuwan, W. Adv. Synth.
Catal. 2006, 348, 1033. (c) Niggemann, M.; Meel, M. J. Angew. Chem. Int. Ed. 2010, 49, 3684.
A similar type of intermolecular FC reaction using highly electronꢀrich aromatic substrates has
been reported, see: (d) Mühlthau, F.; Schuster, O.; Bach, T. J. Am. Chem. Soc. 2005, 127, 9348.
(e) Le Bras, J.; Muzart, J. Tetrahedron 2007, 63, 7942.
(16) Humphrey, G. R; Kuethe, J. T. Chem. Rev. 2006, 106, 2875 and references therein.
(17) When the reaction was performed in TfO–H+ media, the desired product was obtained in
10% yield (GC yield; tridecane as internal standard).
(18) Brand, J. P.; Chevalley, C.; Waser, J. Beilstein J. Org. Chem. 2011, 7, 565.
(19) (a) Yakelis, N. A.; Bergman, R. G. Organometallics 2005, 24, 3579. LiBF4 was used in place
of NaBF4. (b) Golden, J. H.; Mutolo, P. F.; Lobkovsky, E. B.; DiSalvo, F. J. Inorg. Chem. 1994,
33, 5374.
(20) (a) Nava, M. J.; Reed, C. A. Inorg. Chem. 2010, 49, 4726. (b) Peper, S.; Qin, Y.; Almond, P.;
McKee, M.; TeltingꢀDiaz, M.; AlbrechtꢀSchmitt, T.; Bakker, E. Anal. Chem. 2003, 75, 2131.
(21) Xie, Z.; Tsang, C.ꢀW.; Xue, F.; Mak, T. C. W. J. Organomet. Chem. 1999, 577, 197.
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(22) Myasoedov, S. F.; Tsimerinova, T. V.; Solntsev, K. A.; Kuznetsov, N. T. Zhurnal
5
6
Neorganicheskoi Khimii 1984, 29, 1421.
7
8
9
(23) PeñaꢀLópez, M.; AyánꢀVarela, M.; Sarandeses, L. A.; Pérez Sestelo, J. Chem. Eur. J. 2010,
10
11
12
13
14
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18
19
20
21
22
23
24
25
26
27
28
29
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43
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45
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16, 9905.
(24) Yang, S.; Chang, S.; Qiu, D.; Fang, Li, B.; Li, Y.; Z. Shi, Angew. Chem. Int. Ed. 2008, 49,
1473.
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