Reaction of Selectfluor (F-TEDA-BF4) with chloromethylated-DABCO monocation salts (X = BF4, NTf2) and other nitrogen bases (Et3N; Piperidine; basic ionic liquid); Unexpected formation of symmetrical [N-H-N]+ trication salts

Article abstract of DOI:10.1016/j.tetlet.2014.10.071

Selectfluor reacts with N-chloromethylated DABCO monocation BF₄ or NTf₂ salts in MeCN (rt to 80 °C) to give symmetrical [N-H-N]⁺ trication salts. The same dimeric adducts are formed via the reaction of Selectfluor with Et₃N, piperidine, or a basic-IL (imidazolium with an alkyl-piperidine tether). The resulting stable salts were studied by multinuclear NMR, ¹⁵N/¹H HMBC, electrospray-MS, and by chemical reactivity. This hitherto unreported reactivity behavior contrasts the well documented 'transfer fluorination' by Selectfluor to quinuclidine and the quinuclidinic nitrogen of cinchona alkaloids.

Full text of DOI:10.1016/j.tetlet.2014.10.071

Tetrahedron Letters 55 (2014) 6643–6646
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Tetrahedron Letters
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Reaction of Selectfluor (F-TEDA-BF4) with chloromethylated-DABCO
monocation salts (X = BF4, NTf2) and other nitrogen bases (Et3N;
piperidine; basic ionic liquid); unexpected formation of symmetrical
[NÀHÀN]+ trication salts
⇑
Kenneth K. Laali , Arezu Jamalian, Chunqing Zhao
Department of Chemistry, University of North Florida, 1 UNF Drive, Jacksonville, FL 32224, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Selectfluor reacts with N-chloromethylated DABCO monocation BF4 or NTf2 salts in MeCN (rt to 80 °C) to
give symmetrical [NÀHÀN]+ trication salts. The same dimeric adducts are formed via the reaction of
Selectfluor with Et3N, piperidine, or a basic-IL (imidazolium with an alkyl-piperidine tether). The result-
ing stable salts were studied by multinuclear NMR, 15N/1H HMBC, electrospray-MS, and by chemical reac-
tivity. This hitherto unreported reactivity behavior contrasts the well documented ‘transfer fluorination’
by Selectfluor to quinuclidine and the quinuclidinic nitrogen of cinchona alkaloids.
Received 19 September 2014
Revised 9 October 2014
Accepted 10 October 2014
Available online 16 October 2014
Keywords:
Selectfluor
Ó 2014 Elsevier Ltd. All rights reserved.
Chloromethylated DABCO monocation
BF4 and NTf2 salts
Symmetrical [NÀHÀN]+ trication salts
Nitrogen bases
15N NMR
Cl
With its broad-based application as an efficient and selective N–
F fluorinating agent and as mediator or catalyst for oxidative func-
tionalizations,1–3 Selectfluor (F-TEDA-BF4) continues to remain in
the spotlight as a valuable reagent and commodity in synthetic
chemists’ toolbox.4 Rapid transfer-fluorination by Selectfluor to
tertiary nitrogen sites in quinuclidine, pyridine, and 2,4,6-trimeth-
oxypyridine at room temperature is documented in the literature,5
and was applied to the development of enantioselective N–F fluo-
rinating agents based on cinchona alkaloid.6
In the context of a project in our laboratory on the development
and application of task-specific ionic liquids (ILs) we sought to
develop a base-catalyzed fluorination method for certain enoliz-
able ketones and diketones using Selectfluor 1, and employing a
piperidine-appended imidazolium-IL 2 in MeCN solvent (Fig. 1).
A white solid precipitate appeared quickly and continued to
increase on prolonged mixing and subsequent heating (80 °C).
The same observations were made in the absence of the carbonyl
compound, simply by mixing Selectfluor with 2 in MeCN.
N
N
N
N
F
2BF4
Cl
N
1)
(
2
( )
Figure 1. Selectfluor 1 and Basic-IL 2.
same precipitate was observed by reacting 1 with Et3N instead of
piperidine (the reaction was allowed to continue at 80 °C for
2 days). The isolated solid precipitate had good solubility in water,
and NMR studies were performed in D2O. The 1H NMR exhibited
the usual methylene protons and the CH2Cl signals observed for
Selectfluor, but they were all upfield shifted. The 19F NMR showed
that the 46.7 ppm signal (N–F of Selectfluor) was no longer present
and the 19F spectra consisted only of BF4 (d À150.35/À150.36)
along with a signal at d À130.0 ppm.7
More material was recovered by removing MeCN under vac-
uum. The 1H NMR spectra of the isolated crude residue showed it
to be mainly the same compound, but signals stemming from the
employed base were also present (Et3N8 moiety or piperidine
moiety).
When the basic-IL was replaced with piperidine slow formation
of the white solid was again observed after overnight stirring at rt
which increased upon further mixing at 80 °C. The formation of the
The 19F NMR spectrum of the MeCN insoluble and MeCN soluble
salts showed [BF4] along with the signal at À130 ppm but in vari-
able ratios.
⇑
Corresponding author. Tel.: +1 904 620 1503; fax: +1 904 620 3535.
E-mail address: kenneth.laali@UNF.edu (K.K. Laali).
http://dx.doi.org/10.1016/j.tetlet.2014.10.071
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

6644
K. K. Laali et al. / Tetrahedron Letters 55 (2014) 6643–6646
Cl
isolated after removal of solvent have the same cationic constitu-
tion, varying only in the ‘make-up’ of their counterions.
Cl
Cl
N
MeCN
N
+
X
N
N
H
N
N
2BF4
N
N
F
80oC; 3 days
A similar reaction between 1 and the monocation salt 4 resulted
in the formation of two structurally similar adducts, a brownish-
white solid (adduct c) that precipitated out of MeCN, and a brown
residue which was recovered after removing the solvent (adduct
d). The two adducts exhibited the same 1H and 13C NMR spectra
(with slight chemical shift variations due to counter ion effects).
The 19F NMR spectrum of adduct d exhibited resonances for BF4
(À150.5/À150.4) and for CF3 (À79.3) in 6 to 8 ratio, consistent with
[N(SO2CF3)2][2BF4]. For adduct c however, the ratio suggested a
complex counterion ‘richer in BF4’ since the À150 ppm signal was
considerably more intense than expected for [N(SO2CF3)2][2BF4].
Since attempts to obtain suitable crystals for X-ray analysis
from these adducts were unsuccessful, they were subjected to elec-
trospray-MS analysis by direct infusion. Electrospray mass spectra
of 1, 3, and 4 were also recorded for comparison. The significant
ions detected by ES-MS and their assignments are shown in Chart 1.
The ES-MS of parent Selectfluor 1 gave an intense m/z 267 ion
and a cluster ion (at m/z 621.7). The BF4-monocation salt 3 gave
a prominent ion at m/z 161 and a two cation/one anion cluster
(m/z 409/411), and the NTf2-monocation salt 4 exhibited the
Cl
1)
(
(1:1)
3
X = BF4 ( )
3X
X = NTf2 (4)
Figure 2. Reaction of Selectfluor with DABCO-monocation salts.
In subsequent work, the 1:1 reactions between Selectfluor and
the monocations salts 3 and 4 were studied in MeCN.
The 1+3 mixture (1:1 molar ratio) gave the same white precip-
itate in higher yield (adduct a) with identical 1H and 13C NMR to
those of earlier cases, consistent with a symmetrical dimeric
adduct (Fig. 2). Stacked plots showing gradual proton shielding in
the sequence Selectfluor < adduct < 3 and Selectfluor < adduct < 4
(see Fig. 3). More of the white solid material was recovered by
removal of solvent under vacuum (adduct b) with essentially the
same 1H and 13C NMR but with slight variations in chemical shifts.
The 19F NMR showed the signals for BF4 (major) along with the sig-
nal at À130 ppm (minor).
Collectively, the data suggested that less soluble adduct that
precipitated out of MeCN and the more soluble adduct that was
Figure 3. 1H NMR stacked-plot; from top to bottom: Selectfluor (1); adduct a (1+3); DABCO-monocation salt (3); 4.65 ppm signal is H2O in D2O.
Cl
Cl
Cl
Cl
+ BF4
m/z 409/411
N
N
N
N
BF4
N
F
2
2
+ 3
BF4
N
and
N
F
N
and
2
m/z 161
m/z 267
m/z 621.7
1 + 3
Cl
adduct
1 + 4
Cl
adduct
Cl
and
Cl
Cl
Cl
N
N
N
+ NTf2
N
N
N
N
N
2
2
N
+ BF4
+ NTf2
N
N
N
m/z 161
and
and
m/z 601.9
m/z 161
m/z 409/411
m/z 161
m/z 601.9
Chart 1. Significant ions detected by ES-MS for 1, 3, 4, and 1+3 and 1+4 adducts.

K. K. Laali et al. / Tetrahedron Letters 55 (2014) 6643–6646
6645
O
In a control experiment using Selectfluor, compound 5 was
formed in 78% yield (by NMR with the rest being unreacted
TMB). However, when isolated adduct a was allowed to react with
TMB under the same conditions, compound 5 was not detected.10
Returning to NMR studies, proton relaxation times (T1) were
measured for parent 1, monocation salts 2 and 3, and for the iso-
lated adducts in D2O as solvent. It was anticipated that molecular
motion in the dimeric adducts should diminish resulting in lower
T1 values. However, the changes in relaxation times were not sig-
nificant enough to reflect suppression of molecular motion in the
larger, more sterically crowded, adducts.
OMe
Selectfluor (2 equiv)
H2O
MeO
OMe
a
1+3
)
MeO
OMe Adduct (via
F
F
X
H2O
5
112.4 ppm
Figure 4. Control reaction with trimethoxybenzene (TMB).
Cl
N
N
H
N
N
Cl
To gain more insight into the adduct structures in comparison
to those of Selectfluor 1 and the monocation salts 3 and 4, they
were studied by 15N NMR and by 15N/1H HMBC (Chart 2). For the
monocation salts 3 and 4, 15N NMR spectra could be recorded in
either MeCN-d3 or D2O (see Supplementary material) and both ring
nitrogens were detected (the nitrogen signal for [NTf2] in 4 was not
detected).11 To our knowledge, 15N NMR data for Selectfluor 1 have
not been reported. To obtain natural abundance 15N NMR spectrum
for Selectfluor, longer pulse delay had to be employed in order to
detect the N–F nitrogen (Fig. 5). The N-CH2Cl was observed at
À325.3 ppm and the N-F signal was detected at À204.15 ppm,
appearing as a doublet with a JN–F of 85.5 Hz.
3X
-326.8 (adduct a)
-326.9 (adduct c)
-350.6 (adduct a)
-351.3 (adduct c)
-328.4
Cl
Cl
Cl
-328.4
-325.3
N
N
N
N
N
BF4
N
F
NTf2
2BF4
n.o.
-370.3
-370.4
-204.1d (JN-F = 85.5 Hz)
Chart 2. 15N NMR data for the trication salts, monocation salts, and Selectfluor.
Despite the fact that highly concentrated samples of the
adducts had been prepared in D2O for the 15N NMR study, only
the N-CH2Cl nitrogens were observed in 1D 15N NMR. This problem
was overcome via 15N/1H HMBC spectra (Fig. 6 and Supplementary
information) that also confirmed the relative assignment of the
nitrogen signals (only the deshielded nitrogen signal gave a cross
peak with CH2Cl).
The combined data support the formation of symmetrical
[NÀHÀN]+ dimeric trication salts. There is a precedent for the for-
mation of [NÀHÀN]+ monocation salts of DABCO via the reaction of
monocation (m/z 161) and a two cation-one anion cluster (m/z
601.9) Adducts a/b (via 1+3) and c/d (via 1+4) gave the same ions
as those of 3 and 4, respectively, (Chart 1).
Although NMR studies had pointed to cleavage of the N–F bond
in the resulting adducts, confirmatory evidence was sought at this
point based on chemistry. Reaction of two equivalents of Selectflu-
or with 1,3,5-trimethoxybenzene (TMB) in water as solvent
reported by Banks et al.9 leading to the difluoro compound 5 was
selected for reactivity test (see Fig. 4).
Figure 5. 15N NMR spectrum of Selectfluor.

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K. K. Laali et al. / Tetrahedron Letters 55 (2014) 6643–6646
Figure 6. 15N/1H HMBC spectrum of adduct a (via 1+3).
DABCO-HCl and DABCO,12 and the crystal structure of its [B(Ph)4]
salt has been reported.12 Similarly, DABCO-HBF4, DABCO-HClO4,
and DABCO-HReO4 salts have been prepared and studied. These
compounds form hydrogen bonded networks and have unusual
dielectric properties.13
References and notes
1. (a) Stavber, S. Molecules 2011, 16, 6432–6464; (b) Pavlinac, J.; Zupan, M.;
Stavber, S. Molecules 2009, 14, 2394–2409; (c) Stavber, S.; Zupan, M. Acta Chim.
Slov. 2005, 52, 13–26.
2. Nyffeler, P. T.; Duron, S. G.; Burkart, M. D.; Vincent, S. P.; Wong, C.-H. Angew.
Chem., Int. Ed. 2005, 44, 192–212.
3. Stavber, S.; Zupan, M. In Advances in Organic Synthesis; Modern Organofluorine
Chemistry—Synthetic Aspects; Laali, K. K., Ed.; ; Bentham Science Publishers: The
Netherlands, 2006; Vol. 2, pp 213–268.
4. See for example: (a) Teare, H.; Robins, E. G.; Kirjavainen, A.; Forsback, S.;
Sandford, G.; Solin, O.; Luthra, S. K.; Gouverneur, V. Angew. Chem., Int. Ed. 2010,
49, 6821–6824; (b) Yang, Y.; Rao, Y. Org. Lett. 2012, 14, 2874–2877; (c) Ball, L.
T.; Green, M.; Lloyd-Jones, G. C.; Russell, C. A. Org. Lett. 2010, 12, 4724–4727;
(d) Zhou, C.; Li, J.; Lu, B.; Fu, C.; Ma, S. Org. Lett. 2008, 10, 581–583; (e) Laali, K.
K.; Nandi, G. C.; Bunge, S. D. Tetrahedron. Lett 2014, 55, 2401–2405.
5. Abdul-Ghani, M.; Banks, R. E.; Besheesh, M. K.; Sharif, I.; Syvret, R. G. J. Fluorine
Chem. 1995, 73, 255–257.
Formation of [NÀHÀN]+ trication salts in the present study
likely originates from the hydrolysis of [BF4] to generate HF
in situ.14 Formation of the same adducts by reacting Selectfluor
with nitrogen bases in MeCN could be accounted for by slow N+–
F cleavage (homolytic or heterolytic) and formation of N+–H. The
resulting tricationic species are structurally analogous to
[NÀXÀN]+ trication salts formed via the reaction of the monoca-
tion salt 3 with AgBF4/X2 (X = Br, Cl).15
Synthesis of symmetrical [NÀHÀN]+ trication salts via the reac-
tion of Selectfluor with chloromethylated-DABCO/BF4 or/NTf2
monocation salts, or by self-coupling when treated with nitrogen
bases in MeCN, represents a hitherto unreported reactivity channel
that is significantly different from the well documented transfer-
fluorination observed with quinuclidine and quinuclidinic bases.5,6
Additional studies are needed including attempts to grow suitable
crystals for X-ray analysis through anion metathesis protocols.
6. Audouard, C.; Ma, J.-A.; Cahard, D. In Advances in Organic Synthesis; Modern
Organofluorine Chemistry-Synthetic Aspects; Laali, K. K., Ed.; ; Bentham Science
Publishers: The Netherlands, 2006; Vol. 2, pp 431–461.
7. The likely candidate for the À130 ppm signal is BF3, or more logically
BF3/MeCN, but it is unclear how it is associated with the trication salt.
8. Two sets of N-Et groups were present in the 1H NMR spectrum (D2O) of the
recovered residue via the reaction of 1 with Et3N in about 1:1.2 ratio.
9. Banks, R. E.; Besheesh, M. K.; Gorski, R. W.; Lawrence, N. J.; Taylor, A. J.
J. Fluorine Chem. 1999, 96, 129–133.
10. The 1H NMR of the crude reaction mixture (after removal of water) showed
essentially unreacted TMB along with traces of unknown by-products. 19F NMR
exhibited a tiny signal at À153 ppm (BF4) along with 2 minor peaks at À78.4
and À81.3 ppm. There was no signal for ring fluorinated TMB either (expected
at À167.5 ppm).9
Acknowledgements
K.L. thanks UNF for the award of Presidential Professorship.
11. 15N NMR chemical shift of AgNTf2 has been reported at 141.7 (from NH3) which
is equivalent to À240.3 ppm from MeNO2; see Levya-Perez, A.; Corma, A.;
Cabrero-Antonino, J. R. Chem. Eur. J. 2013, 19, 8627–8633.
Supplementary data
12. Bock, H.; Vaupel, T.; Schödel, H.; Koch, U.; Egert, E. Tetrahedron. Lett 1994, 35,
7355–7358.
13. Szafranski, M. J. Phys. Chem. B 2009, 113, 9479–9488.
14. Olivier-Bourbigou, H.; Magna, L.; Morvan, D. Appl. Catal., A General 2010, 373,
1–56.
15. Wang, Y.-M.; Wu, J.; Hoong, C.; Rauniyar, V.; Toste, F. D. J. Am. Chem. Soc. 2012,
134, 12928–12931.
Supplementary data (experimental procedures, NMR data, and
selected 15N NMR and 15N/1H HMBC spectra (Figs. S1–S5)) associ-
ated with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2014.10.071.