2-(Pyridinium-1-yl)-1,1-bis(triflyl)ethanides: Structural behaviour and availability as bis(triflyl)ethylating reagents

Article abstract of DOI:10.1039/c3cc46171h

Stable and easy-to-handle zwitterions containing carbanion and pyridinium moieties were synthesized, and their structural studies by both X-ray crystallography and theoretical methods revealed the stereoelectronic effect in the zwitterionic 'C^-

Full text of DOI:10.1039/c3cc46171h

ChemComm
View Article Online
View Journal | View Issue
COMMUNICATION
2-(Pyridinium-1-yl)-1,1-bis(triflyl)ethanides: structural
behaviour and availability as bis(triflyl)ethylating
reagents†
Cite this: Chem. Commun., 2013,
49, 10091
Received 12th August 2013,
Accepted 3rd September 2013
Hikaru Yanai,* Yoichi Takahashi, Haruhiko Fukaya, Yasuo Dobashi and
Takashi Matsumoto
DOI: 10.1039/c3cc46171h
www.rsc.org/chemcomm
Stable and easy-to-handle zwitterions containing carbanion and
pyridinium moieties were synthesized, and their structural studies
by both X-ray crystallography and theoretical methods revealed the
stereoelectronic effect in the zwitterionic ‘CÀ–C–N+’ system.
The stereoelectronic effect is a fundamental concept in modern
organic chemistry. Several textbooks1 on this effect discuss an
‘anomeric effect’ in 2-alkoxytetrahydropyrans including pyranose
derivatives2 and a ‘gauche effect’ in 1,2-difluoroethane.3 The origin
of these effects on the molecular conformation is not straightforward;
however, the donor–acceptor orbital interactions, referred to as ‘n–s*
delocalization’ and the ‘antiperiplanar effect’, are the most common
explanations at present.
In general, in the ‘X–C–Y’ systems, the delocalization of a lone
electron pair (nX) on the X atom to the antibonding orbital (s*C–Y) in
the C–Y part plays a crucial role in stabilizing the conformation. In
particular, this donor–acceptor interaction has been well documented
in several O–C–Y systems that contain highly polarized C–Y acceptors
(Fig. 1). A number of theoretical studies have also demonstrated that
the lone electron pair on the anionic carbon atom performs as an
effective donor for this type of interaction. However, in cases of
carbanions substituted by hetero atoms at the b position,4 experi-
mental evidence of this interaction (negative hyperconjugation) is
scarce because such species fragment rapidly. For example, the
Fig. 1 nO–s*C–X delocalization in ROCH2X and the fragmentation reaction of
R2CÀCH2X.
barbituric acid and thiobarbituric acid, respectively, have also been
isolated. In addition, Koshar and co-workers have reported that the
reaction of 1,1-bis(triflyl)ethylene with pyridine gives a zwitterion 2a
containing a carbanion moiety stabilized by gem-substitution with
two triflyl groups in moderate yield.8,9
These zwitterionic ‘CÀ–C–N+’ systems are interesting from the
dehydration reaction of b-hydroxycarbonyls via the E1cb mechanism viewpoint of experimental studies on the negative hyperconjugation.
and the fragmentation reaction of b-halogenated ethers using zinc, Herein, we describe a general and convenient method for the
the so-called Boord reaction, have been used as common organic synthesis of 2-(pyridinium-1-yl)-1,1-bis(triflyl)ethanides including
reactions to construct alkene functionalities.
Koshar’s zwitterion 2a; we also report the results of the structural
Exceptionally, such reactions require relatively hash conditions in analyses of these compounds to determine the evidence of the donor–
cases where the carbanions are highly stabilized by substituent acceptor interactions. Furthermore, we successfully used the zwitter-
effects. For instance, Zia-Ebrahimi and co-workers synthesized ions as new reagents for incorporating the Tf2CH (Tf = CF3SO2)
zwitterion 1a, which bears both a pyridinium part and an enolate functionality into neutral organic molecules. The carbon acids thus
moiety in its structure.5 Similar zwitterions 1b6 and 1c7 derived from obtained are known to be one of the most effective Brønsted acid
catalysts for C–C bond forming reactions using silicon enolates.10,11
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences,
We first attempted to improve the synthetic procedure for zwitter-
ion 2a. In 1976, Koshar and co-workers reported that the reaction of
Tf2CH2 3 and paraformaldehyde gives a mixture of Tf2CQCH2 and
1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. E-mail: yanai@toyaku.ac.jp
† Electronic supplementary information (ESI) available: Details of experiments,
NMR data for all new compounds, and crystal structures of 2a–2n. CCDC 948820–
Tf2CHCH3 in a ratio of 42 : 58, and the following treatment with
948832. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3cc46171h
pyridine results in the formation of 2a in 41% yield from 3.8 On the
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 10091--10093 10091

View Article Online
Communication
ChemComm
structure of 2b, the anionic nature of C7 was fully supported by its
planar structure because the bond angles around C7 are 120.21
(S2–C7–S1), 120.61 (S1–C7–C6), and 118.91 (C6–C7–S2). A comparison
of the bond lengths of S1–C8 (184.9 pm) and S2–C9 (185.1 pm) with
those of C7–S1 (168.2 pm) and C7–S2 (168.6 pm) revealed that the
latter bond lengths were notably shorter. This result also suggested
the delocalization of the lone electron pair (nC7) on C7, which
occupies a p orbital to s* orbitals of S1–C8 and S2–C9.15 Similar
tendencies with respect to the structure of the anionic carbon and
the bond lengths were also observed in the case of 2h. However, the
Scheme 1 Improved synthesis of Koshar’s zwitterion 2a.
other hand, we examined a more convenient three-component reac- relative position of two trifluoromethyl groups is different for both
tion of Tf2CH2 3, paraformaldehyde, and pyridine. After some structures, i.e. two trifluoromethyl groups in 2b existed in an
attempts, we found that simply mixing these compounds for 4 h at extended manner (anti form), whereas the folded conformation of
60 1C in 1,2-dichloroethane (DCE) solvent resulted in the formation of two trifluoromethyl groups (syn form) was observed in 2h. In the
the desired zwitterion 2a in quantitative yield (Scheme 1). This finding crystal structures of all zwitterions, the conformation was either the
demonstrates that the condensation reaction between strongly acidic anti form or syn form. Zwitterions 2a–2f and 2k–2n, which were
Tf2CH2 312 and formaldehyde, which gives rise to Tf2CQCH2, derived from pyridine itself, 2-alkylpyridines, 2-methoxypyridine,
proceeds in the presence of basic pyridine. Furthermore, a stepwise oxazole and imidazoles, exhibited the anti form. On the other hand,
reaction procedure was also effective in producing 2a. For instance, zwitterions 2g–2j, which were derived from 2-halopyridines and
after a mixture of 3 and paraformaldehyde in the presence of a small quinoline, exhibited the syn form. The bis(triflyl)methyl (Tf2CH)
amount of water was stirred for 6 h at room temperature, the resultant group is known to be a strong C–H acidic functionality owing to
product was treated with pyridine to give 2a in 70% yield.13 In both gem-disubstitution of the carbon atom by two triflyl groups.12,16
cases, we isolated acceptably pure 2a by simply washing the resulting Therefore, it is not surprising that the zwitterions containing highly
precipitate with CHCl3.
stabilized carbanion moieties are isolable.10a,17
On the basis of these results, we next conducted the three-
In the zwitterionic ‘C1À–C2–N+’ systems (Table 1), the C1–C2 and
component reaction of Tf2CH2 3, paraformaldehyde and several C2–N bond lengths and the S–C1–C2–N torsions suggest that an nC1–
pyridines (Fig. 2).14 Under similar conditions, the reactions in which s*C2–N interaction occurs. The shortening of the C1–C2 length and
2-methyl, 2-ethyl, and 2-isobutylpyridines were used gave the corre- simultaneous elongation of the C2–N length owing to an increase in
sponding zwitterions 2b, 2c and 2d, respectively, in excellent yields. this donor–acceptor interaction are easily predicted. Furthermore, this
The three-component reaction using 2-isopyopylpyridine did not interaction would be maximized when a p orbital occupied by nC1 well
result in the formation of the desired zwitterion 2e, whereas overlaps with a s*C2–N orbital (torsions of S–C1–C2–N E 901). A
the reaction performed in a stepwise manner produced 2e in 53% comparison of the known crystal structure of 3-(1-pyridinio)propane-
yield. In contrast, sterically bulky 2,6-dimethylpyridine was not con- sulfonate 418 reveals that the C1–C2 lengths of the pyridinium-based
verted into the corresponding zwitterion under either set of reaction zwitterions 2a–2i are short (148.0 to 150.1 pm). The C2–N lengths
conditions. The three-component reaction using 2-methoxypyridine (150.6 to 153.0 pm) in 2a–2i are notably elongated. In addition, the
smoothly proceeded to give the zwitterion 2f in 99% yield. Likewise, torsions f and y in these crystal structures are within the acceptable
the reactions with 2-halogenated pyridines gave the zwitterions 2g–2i range for the donor–acceptor interaction.
in excellent yields. Some nitrogen-containing heterocycles were also
The natural bond orbital (NBO) analysis also demonstrated
applicable for this transformation. For instance, quinoline, oxazole theoretical support for the donor–acceptor interactions including the
and imidazoles were converted into the zwitterions 2j–2n, respectively. nC1–s*C2–N interaction (see ESI†). The NBO calculation on the anti
To confirm the zwitterionic structure of these products, we conformer of 2-methylpyridinium 2b showed strong interactions not
conducted X-ray crystallographic analyses. The crystallographic only between nC1 and two s*S–CF3 orbitals (27.13 and 24.77 kcal molÀ1
)
structures of 2-methylpyridinium 2b and 2-chloropyridinium but also between nC1 and a s*C2–N orbital (24.22 kcal molÀ1).
2h are shown in Fig. 3(A) and (B), respectively. In the crystal Similar orbital interactions were also observed in the NBO analysis
Fig. 2 Three-component reaction of Tf2CH2 3, paraformaldehyde, and nitrogen-containing heterocycles.
c
10092 Chem. Commun., 2013, 49, 10091--10093
This journal is The Royal Society of Chemistry 2013

View Article Online
ChemComm
Communication
Scheme 2 Bis(triflyl)ethylation reaction of p-cresol.
In summary, we have successfully synthesized 2-(pyridinum-1-yl)-
1,1-bis(triflyl)ethanides from a wide range of 2-substituted pyridines.
The zwitterionic structures of the products were confirmed by not
only their NMR spectra but also X-ray crystallographic analyses.
Because these zwitterions were stable, nonhygroscopic and easy-to-
handle, the stereoelectronic effect in the zwitterionic ‘CÀ–C–N+’
system was investigated. In addition, 2-fluoropyridinium 2g can be
used as a reagent to incorporate the acidic Tf2CH group into an
electronically rich arene framework.
Fig. 3 ORTEP drawing. The thermal ellipsoids are shown at 50% probability.
(A) 2-Methylpyridinium 2b, (B) 2-chloropyridinium 2h.
This study was partially supported by a Grant-in-Aid for
Scientific Research on Innovative Areas ‘Advanced Molecular
Transformations by Organocatalysts’ from the MEXT and by the
Asahi Glass Foundation.
Table 1 Bond lengths and torsions of zwitterions based on X-ray crystallo-
graphic analyses
Notes and references
1 P. Deslongchamps, Stereoelectronic Effects in Organic Chemistry,
Pergamon Press, Oxford, UK, 1983; A. J. Kirby, Stereoelectronic
Effects, Oxford University Press, Oxford, UK, 1996.
2 E. Juaristi and G. Cuevas, Tetrahedron, 1992, 48, 5019.
3 D. O’Hagan, J. Org. Chem., 2012, 77, 3689.
Bond lengths/pm
Torsions/1
4 D. A. Dixon, T. Fukunaga and B. E. Smart, J. Am. Chem. Soc., 1986,
108, 4027; P. v. R. Schleyer and A. J. Kos, Tetrahedron, 1983, 39, 1141.
5 M. Zia-Ebrahimi and G. W. Huffman, Synthesis, 1996, 215.
6 N. Kuhn, A. Al-Sheikh, S. Schwarz and M. Steimann, Z. Naturforsch.,
B: J. Chem. Sci., 2005, 60, 398.
2
R
Conformer
C1–C2
C2–N
f
y
2aa
2b
2e
H
anti
anti
anti
anti
syn
149.5
149.7
149.5
150.1
149.0
148.0
151.6
152.2
151.6
150.6
153.0
152.9
À97.9
À78.2
À107.7
À78.1
À83.0
À83.5
90.5
CH3
i-Pr
OCH3
F
108.2
81.8
113.0
95.0
¨
7 K. Sweidan, M. A. AlDamen, C. Maichle-Moßmer and M. S. Mubarak,
2f
2ga
2i
J. Chem. Crystallogr., 2012, 42, 427.
8 L. L. Barber Jr and R. J. Koshar, US Pat., 3 962 342, 1976.
9 Zhu reported the reaction of some 1,1-bis(triflyl)alkenes with pyr-
idine, although structural determination of the products was mis-
taken. See: S.-Z. Zhu, Synthesis, 1994, 261.
Br
syn
98.9
a
Average value of the conformers composing a unit cell.
10 H. Yanai, T. Yoshino, M. Fujita, H. Fukaya, A. Kotani, F. Kusu and
T. Taguchi, Angew. Chem., Int. Ed., 2013, 52, 1560; H. Yanai, H. Ogura,
H. Fukaya, A. Kotani, F. Kusu and T. Taguchi, Chem.–Eur. J., 2011,
17, 11747; H. Yanai and T. Taguchi, Chem. Commun., 2012, 48, 8967.
11 Examples of acid catalysts bearing a Tf2CH group, see: K. Ishihara,
A. Hasegawa and H. Yamamoto, Angew. Chem., Int. Ed., 2001,
40, 4077; K. Ishihara, A. Hasegawa and H. Yamamoto, Synlett,
2002, 1299; A. Hasegawa, Y. Naganawa, M. Fushimi, K. Ishihara
and H. Yamamoto, Org. Lett., 2006, 8, 3175; A. Takahashi, H. Yanai
and T. Taguchi, Chem. Commun., 2008, 2385.
12 The pKa value of Tf2CH2 3 in DMSO is measured to be 2.1 and this
value means that 3 performs as the stronger proton donor relative to
trifluoroacetic acid (pKa in DMSO = 3.45), see: F. G. Bordwell, Acc.
Chem. Res., 1988, 21, 456.
of the syn conformer of 2-chloropyridinium 2h (nC1–s*S–CF3
interactions, 25.08 and 25.08 kcal molÀ1; nC1–s*C2–N inter-
action, 31.27 kcal molÀ1). These results indicate that the
delocalization of the lone electron pair on the anionic carbon
atom to the three s* orbitals (negative hyperconjugation) plays
a critical role in stabilizing the molecular structure.
As an application of the present zwitterions, we found that
some zwitterions can be used as new reagents for incorporating
the Tf2CH functionality into the molecular structure of neutral
organic compounds (Scheme 2). Zwitterion 2a slowly reacted with
neutral nucleophiles such as p-cresol, whereas the reaction of
2-fluoropyridinium 2g proceeded at room temperature in aceto-
13 We found that addition of water is effective to inhibit formation of
side products such as Tf2CHCH2CHTf2 and Tf2CHCH3.
14 H. Yanai, M. Fujita and T. Taguchi, Chem. Commun., 2011, 47, 7245.
nitrile to give the desired carbon acid 5 in 92% yield. This carbon 15 G. Raabe, H.-J. Gais and J. Fleischhauer, J. Am. Chem. Soc., 1996,
118, 4622.
acid can be used as an acid catalyst for the Mukaiyama aldol
16 For the gas phase acidities, see: I. A. Koppel, R. W. Taft, F. Anvia,
reaction.10b Interestingly, 2-methylpyridinium 2b, quinolinium 2j
S.-Z. Zhu, L.-Q. Hu, K.-S. Sung, D. D. DesMarteau, L. M. Yagupolskii, Y. L.
and imidazolium 2m could not be used as the bis(triflyl)ethylating
reagents under the same conditions. In contrast, 2-chloro-
pyridinium 2h and oxazolium 2k showed suitable reactivity (see
ESI†). This reactivity can be rationalized by considering the pKaH
values of the heterocyclic amines. That is, zwitterions derived
from heterocyclic amines which show low pKaH values showed
relatively high reactivity in this reaction.
Yagupolskii, N. V. Ignat’ev, N. V. Kondratenko, A. Y. Volkonskii, V. M.
Vlasov, R. Notario and P.-C. Maria, J. Am. Chem. Soc., 1994, 116, 3047.
17 Examples of intermolecular salts, see: A. Hasegawa, T. Ishikawa,
K. Ishihara and H. Yamamoto, Bull. Chem. Soc. Jpn., 2005, 78, 1401;
M. Ochiai, N. Tada, K. Murai, S. Goto and M. Shiro, J. Am. Chem.
Soc., 2006, 128, 9608.
18 K. D. Koclega, M. Chruszcz, A. Gawlicka-Chruszcz, M. Cymborowski
and W. Minor, Acta Crystallogr., Sect. C: Cryst. Struct. Commun.,
2007, 63, o114.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 10091--10093 10093