Preparation, structures and preliminary host-guest studies of fluorinated syn-bis-quinoxaline molecular tweezers

Article abstract of DOI:10.3762/bjoc.6.39

A series of polycyclic frameworks with fluorinated syn-facial quinoxaline sidewalls has been prepared as potential molecular tweezers for electron-rich guest compounds. Our synthetic route to the cyclooctadiene-derived scaffolds 16a-d takes advantage of the facile isolation of a novel spirocyclic precursor 9b with the crucial syn-orientation of its two alkene moieties. The crystal structure of 16c displays two features typical of a molecular tweezer: inclusion of a solvent molecule in the molecular cleft and self-association of the self-complementary scaffolds. Furthermore, host-guest NMR studies of compound 16c in solution show chemical exchange between the unbound and bound electron-rich guest, N,N,N',N'-tetramethyl-p-phenylenediamine.

Full text of DOI:10.3762/bjoc.6.39

Preparation, structures and preliminary host–guest
studies of fluorinated syn-bis-quinoxaline
molecular tweezers
Markus Etzkorn*1, Jacob C. Timmerman1, Matthew D. Brooker1, Xin Yu2
and Michael Gerken2
Preliminary Communication
Open Access
Address:
Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
1Department of Chemistry, The University of North Carolina at
Charlotte, 9201 University City Blvd., Charlotte, NC 28223, USA and
2Department of Chemistry and Biochemistry, University of Lethbridge,
Lethbridge, AB T1K 3M4, Canada
doi:10.3762/bjoc.6.39
Received: 31 December 2009
Accepted: 23 March 2010
Published: 20 April 2010
Email:
Markus Etzkorn* - metzkorn@uncc.edu
Guest Editor: D. O’Hagan
* Corresponding author
© 2010 Etzkorn et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
crystal structure; fluorine; molecular tweezers; quinoxalines;
self-association
Abstract
A series of polycyclic frameworks with fluorinated syn-facial quinoxaline sidewalls has been prepared as potential
molecular tweezers for electron-rich guest compounds. Our synthetic route to the cyclooctadiene-derived scaffolds 16a–d takes
advantage of the facile isolation of a novel spirocyclic precursor 9b with the crucial syn-orientation of its two alkene moieties. The
crystal structure of 16c displays two features typical of a molecular tweezer: inclusion of a solvent molecule in the molecular cleft
and self-association of the self-complementary scaffolds. Furthermore, host–guest NMR studies of compound 16c in solution show
chemical exchange between the unbound and bound electron-rich guest, N,N,N′,N′-tetramethyl-p-phenylenediamine.
Introduction
A broad variety of structurally diverse molecular tweezers, (Scheme 1), but so far only a few groups have investigated
i.e., scaffolds in which a tether unit connects two these intriguing target compounds: Korenaga and Sakai opti-
syn-oriented aromatic pincers, are well-established as devices mized the synthetic access to fluorinated acridine-based
for the molecular recognition of mostly electron-deficient guest molecular tweezers 1 and determined association constants for
compounds [1-10]. Conversely, molecular tweezers with a the complexation of electron-rich arenes [14,15]. Hermida-
binding cleft that displays an inverted electrostatic potential Ramón and Estévez calculated the structures and
could thus find application in sensing of electron-rich guests, or electrostatic potentials of belt-shaped compounds 2a–c and
even anions [11-13]. Possible frameworks include the seem- predicted the complexation of halide anions in the cavity of 2c
ingly trivial fluorinated analogues of known frameworks [16-18].
Page 1 of 7
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
Scheme 1: Fluorinated molecular tweezers.
Intrigued by Chou’s communication on the spectroscopic prop- conditions and delivered a dark crude product with unspecified
erties of non-fluorinated bis-quinoxalines of type 3 and 4a [19], tarry material after heating the substrates for several days to
we targeted on the corresponding fluorinated derivatives – in 115 °C (1H and 19F NMR control). Occasionally, the condensa-
particular compound 4b with its large binding cleft.
tion reaction did not lead to complete conversion of the
tetraketone precursor 10 and produced a separable mixture of
In this paper, we present the synthesis and characterization of the mono- and bis-condensation products 13 and 15, respect-
these synthetically more challenging derivatives. Furthermore, ively. The isolated mono-adducts 13a (or 13b) could then be
we discuss structural features of a cyclooctadiene-derived scaf- converted to the symmetrical target 15a (or 15c) or, upon con-
fold of type 4b and report preliminary spectroscopic data on densation with the appropriate o-phenylenediamine derivative
their association with electron-rich guest compounds.
12c (or 12a), to scaffold 15b with only one fluorinated quinox-
aline subunit.
Results and Discussion
Synthesis of fluorinated bis-quinoxalines
The synthetic access to cyclooctadiene-derived scaffolds is
The general route [19] to bis-quinoxaline targets (Scheme 2) complicated by the lack of selectivity in the twofold
utilizes a twofold Diels–Alder reaction of a cycloalkadiene (5,6) Diels–Alder reaction of diene 6 and led to a mixture of the syn-
with cyclopentadienone derivatives (7), subsequent oxidation of and anti-bis-adducts in a 1:4 ratio [26,27]. Since the separation
the syn-diene intermediates (8,9) to their corresponding of the crucial syn-isomer 9a from anti-compound 9a′ by
tetraketones (10,11) and condensation of the latter with repeated recrystallization did not furnish the pure
o-phenylenediamine derivatives (12) to obtain the syn-bis- endo,endo,syn-isomer 9a in our hands, we focused on the new
quinoxaline target compounds (15,16). This synthetic route is spirocyclic derivative 9b. Thus, reaction of the spiro-ketal 7b
flexible with regard to the tether size (cyclohexane vs [28] with cyclooctadiene (6) furnished a mixture of 9b and 9b′
cyclooctane) and modifications in the pincer sidewalls (degree in excellent yield in the same ratio of isomers as observed in the
of fluorination).
previous case. Again, the endo,endo,syn-isomer 9b could not be
satisfactorily separated from the endo,endo,anti-isomer 9b′ by
Although only the larger cyclooctadiene-derived scaffolds chromatography, but gram-amounts of the crucial syn-isomer
16a–d could function as molecular tweezers, we also synthe- 9b were readily obtained after repeated recrystallization from
sized the fluorinated cyclohexadiene-derived compounds 15b–d hot diethyl ether. The assignment of both syn- and anti-isomers
with their smaller π-π–distances. A Diels–Alder reaction of was initially based on 1H NMR spectroscopic analogies to the
cyclohexadiene (5) with ketal 7a furnished exclusively the syn- bis-methoxyketals, i.e., the small low-frequency shift of the
bis-adduct 8a [20] which was then converted to the canary- bridgehead proton resonances of the anti-adduct (Δδ =
yellow tetraketone 10 by Khan’s original RuCl3-catalyzed oxi- 0.20 ppm). The X-ray structure determination of target com-
dation protocol [21-23] since Chou’s “optimized” procedure pound 16c confirmed indirectly the correct assignment of
was somewhat capricious in our hands. The twofold condensa- isomers 9b and 9b′ (vide infra). Oxidation of 9b with Khan’s
tion with di- or tetrafluoro-o-phenylenediamine (12b,c) [24,25] original protocol [21-23] and condensation of the resulting
provided access to the novel fluorinated species 15b–c in tetraketone 11 with o-phenylenediamine 12a or the fluorinated
acceptable yields (60–70%). This last reaction required harsh derivatives 12b–c resulted in the new non-fluorinated parent
Page 2 of 7
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
Scheme 2: Synthesis of non-fluorinated and fluorinated syn-bis-quinoxalines.
compound 16a and the three fluorinated scaffolds 16b–c, acetonitrile and methylene chloride solutions. The spectro-
respectively. All new syn-bis-quinoxalines were purified by scopic characteristics of 15a and several non-fluorinated deriva-
flash-chromatography on silica gel and obtained as off-white tives have been described elsewhere [19] and the NMR spectro-
powders in 60–75% yield after recrystallization from methanol. scopic data for 15b–c (16a–d) are only altered by the absence
Considering the low nucleophilicity of the fluorinated amine of the corresponding proton resonances, the additional coupling
building blocks 12b–c, our yields in the condensation reaction of fluorine with either the arene protons in 15c (16c) or the
are quite good (71–86% for each condensation step) and any aromatic carbon atoms, and the more complex signal structure
modification of the reaction conditions by other reported of the spirocyclic ketal in 16a–d. The UV–vis spectra (avail-
procedures [29-32] did not significantly alter the outcome. It able in the Supporting Information File 1) display the expected
should be noted that all fluorinated bis-quinoxalines are stable electronic transitions for quinoxaline derivatives [33-35], i.e., a
compounds which do not show any decomposition over prominent π,π* transition with λmax between 236–245 nm and a
extended periods of time; loss of fluorine has only been lower intensity n,π* transition with λmax between 312–316 nm
observed under typical nucleophilic aromatic substitution condi- with a poorly resolved vibrational structure. The spectra of the
tions.
cyclohexadiene-derived scaffolds 15 and the cyclooctadiene-
derived frameworks 16 are very similar. Within each series we
Although the new compounds, in particular the cyclohexadiene- could not observe a gradual blue-shift for the electronic trans-
derived species 15b–c, were reasonably soluble in dipolar itions as the degree of fluorination increased from 15a (16a) to
aprotic solvents (DMSO, DMF) or halogenated aromatic 15c (16c), a result that is in accord with Chou’s UV–vis data for
solvents (C6H5Cl), they only displayed poor solubility in differently substituted bis-quinoxaline scaffolds that abstain
several standard organic solvents (CHCl3, CH2Cl2, CH3OH, from clear trends as the electronic-withdrawing character of the
C6H6, CH3CN). Their full characterization and some prelim- substituents were altered [19]. The ESI-mass spectra (aceto-
inary host–guest studies of the cyclooctadiene-derived frame- nitrile, acetic acid) of all new syn-bis-quinoxalines show the
works could however, be carried out in dilute chloroform, correct isotopic pattern of the protonated molecules and, inter-
Page 3 of 7
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
estingly, display mass clusters for the protonated “dimers” of
compounds 15b and 16b. Nevertheless, any interpretation of the
nature of these latter species (proton-bridged “dimer”, proton-
ated π-π–aggregate, protonated self-associated “dimer”)
requires further investigation and cannot be easily transferred to
the solution- or solid-state structures of the neutral tweezer
compounds [36].
Table 1: Crystallographic details for 16c and related non-fluorinated
compounds.
16c
4a [19]
3 [19]
crystal
system
monoclinic
monoclinic
orthorhombic
space group P21/n
P21/c
3.16
Pbcn
3.70
R [%]
3.79
d1 [Å]a
d2 [Å]a
8.144
10.004
7.907
9.641
45.03
4.686
4.135
−14.41
Structures
We were able to grow single crystals of the octafluoro com-
pound 16c from acetonitrile or chloroform solutions suitable for
X-ray structure determination (Table 1, Figure 1). In each case,
the crystals contained residual ethyl acetate from the purifica-
tion step, indicating strong binding of the ethyl acetate molecule
bite angle [°]b 46.68
adefined in Scheme 2.
ba negative bite angle defines U- vs. V-shaped tweezers.
inside the binding cleft of 16c. Compound 16c crystallizes, with quite common in many other molecular tweezer scaffolds
an ethyl acetate solvent molecule, in the monoclinic system [1-10]. Compound 16c shows the typical orientation of fluorine
(space group: P21/n) and displays bond lengths and angles in substituents of one pincer sidewall over the arene subunit of
the expected ranges. The ethyl acetate displays a small degree another tweezer (substituent distances to arene plane: 3.283 Å,
of orientation disorder (11.8%). Figure 1a shows a thermal 3.315 Å), interpreted as the attractive interaction between
ellipsoid image of 16c and Figure 1b depicts the packing within fluorine substituents with the electron-depleted fluoroarene
a unit cell setting. The large binding pocket of syn-bis-quinox- subunit [37,38]. The centroid-centroid distances (d1, d2) and the
aline 16c provides enough space to allow the association with bite angle between the two quinoxaline sidewalls of the binding
solvent (ethyl acetate) and, through “dimer formation”, with the pocket in fluorinated framework 16c differ only slightly from
pincer sidewall of a second tweezer molecule. The “dimer” as- the parameters of the non-fluorinated compound 4a, although
sociation of fluorinated molecular tweezers in the solid state has the latter does not include any solvent in the cleft and, further-
been observed for the acridine-derived scaffold 1 [15] and is more, lacks the interpenetrating self-association displayed in
Figure 1: (a) Thermal ellipsoid image of the tweezer molecular 16c in the structure 16c · CH3CO2C2H5; thermal ellipsoids are drawn at the 50% prob-
ability level. (b) View of the packing of 16c in the unit cell (two CH3CO2C2H5 molecules are omitted for clarity). [C34H20Cl4F8N4O4 · CH3CO2C2H5,
MW = 930.44, monoclinic, space group P21/n, a = 15.3990(12) Å, b = 14.0635(11) Å, c = 17.7148(14) Å, β = 94.6470(10)°, V = 3823.8(5) Å3, Z = 4,
dcalc = 1.616 g cm−3, T = 153(2) K, λ = 0.71073 Å, 44247 reflections measured, 9378 unique (Rint = 0.017), final R1 [I > 2δ(I)] = 0.0343 and R1 =
0.0403 (wR2 = 0.0952) for all data; CCDC deposit # 786086.
Page 4 of 7
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
16c [19]. Conversely, 4a shows π-π–interaction of two adjacent binding cleft, the effect of eight fluorine substituents on the
molecules by stacking two pincer sidewalls, each from the electrostatic potential within the cleft is paramount in the facili-
outside (U···U geometry).
tation of this interaction between host and guest.
Host–Guest Chemistry
Although none of the reported cyclooctadiene-derived syn-bis-
quinoxaline scaffolds [19] has been established as a molecular
tweezer, the general architecture with two syn-oriented aromatic
sidewalls and a large π-π–distance does allow the accommoda-
tion of guest compounds as demonstrated in the crystal struc-
ture of 16c. Whilst most molecular tweezers have a typical cleft
size of ca. 7 Å, several functional larger systems have been
reported [39,40]. Figure 2 shows the electrostatic potential
surfaces of compounds 16a–c, depicting the inversion of the
electrostatic potential in the pincer subunits upon increasing the
degree of fluorination.
Figure 3: 1H NMR spectra (CD2Cl2, 500 MHz) of 16c (host [black])
upon titration with N,N,N′,N′-tetramethyl-p-phenylenediamine (guest
[red]); host concentration: 0.01M; host–guest ratio: 1:2 (1), 1:5 (2),
1:10 (3), 1:20 (4).
Korenaga and Sakai have already noted that N,N,N′,N′-tetra-
methyl-p-phenylendiamine displays a stronger association
constant with molecular tweezer 1 when compared to several
other electron-rich aromatic guest compounds. This behavior
was explained by the large magnitude of the former guest’s
quadrupole moment [15].
Figure 2: Electrostatic potential surfaces of 16a–c (Spartan 06 [41]:
B3LYP/6-31G*//B3LYP/6-31G*; legend in kcal/mol).
NMR titration experiments with electron-rich arenes (1,4-
dimethoxybenzene, 1,3,5-trimethoxybenzene, N,N-dimethyl- With our preliminary NMR titrations we could demonstrate that
aniline, N,N,N′,N′-tetramethyl-p-phenylenediamine) were scaffold 16 can indeed associate with an external guest com-
carried out in deuterated methylene chloride solution for the pound in solution if the host and guest units are matched appro-
four cyclooctadiene-derived species 16a–d. Interestingly, only priately. Further experiments employing complementary analyt-
the octafluoro-derivative 16c showed line-broadening of the 1H ical techniques, e.g., isothermal calorimetry, as well as addition-
resonances for one guest compound, i.e., N,N,N′,N′-tetramethyl- al investigations of the host–guest chemistry with suitable,
p-phenylenediamine, at various host–guest ratios (Figure 3). No larger guest compounds, will provide detailed thermodynamic
changes in chemical shift of the quinoxaline 19F resonances parameters of the host–guest association, and possibly a better
were observed in the 19F NMR spectra. Upon cooling the NMR host–guest match, respectively.
samples the guest’s aromatic and methyl 1H resonances
sharpened only to less broad signals. Titration of 16c with other Conclusion
electron-rich aromatic guest compounds (1,4-dimethoxyben- The synthesis of fluorinated syn-bis-quinoxalines (15b–c,
zene, 1,3,5-trimethoxybenzene, N,N-dimethylaniline) under the 16b–c) was successfully accomplished by a three-step
same conditions showed only the original host and guest reson- procedure, utilizing the new, readily isolable spirocyclic syn-de-
ances in the 1H NMR spectra without any line broadening, rivative 9b as an entry towards the larger cyclooctadiene-
which indicates that there was no interaction between these derived scaffold 16. The crystal structure of 16c clearly demon-
three molecules with the tweezer’s cavity. It is important to note strates that syn-bis-quinoxaline frameworks can function as
that from the entire series of compounds, only the highly fluor- molecular tweezers. Furthermore, preliminary NMR spectro-
inated scaffold 16c shows chemical exchange between the scopic titration experiments with the octafluoro-syn-bis-quinox-
unbound and bound guest, N,N,N′,N′-tetramethyl-p-phenylene- aline 16c prove the interaction of an external, electron-rich
diamine. While this facile exchange is certainly due to the large guest with the molecular tweezer’s cavity in solution.
Page 5 of 7
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
16.Mandado, M.; Hermida-Ramón, J. M.; Estévez, C. M. THEOCHEM
2006, 854, 1–9.
Supporting Information
17.Hermida-Ramón, J. M.; Estévez, C. M. Chem.–Eur. J. 2007, 13,
4743–4749. doi:10.1002/chem.200601836
Supporting Information File 1
Experimental details and characterization data for all new
compounds.
18.Hermida-Ramón, J. M.; Mandado, M.; Sánchez-Lozano, M.;
Estévez, C. M. Phys. Chem. Chem. Phys. 2010, 12, 164–169.
doi:10.1039/b915483c
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-6-39-S1.pdf]
19.Chou, T.-C.; Liao, K.-C.; Lin, J.-J. Org. Lett. 2005, 7, 4843–4846.
doi:10.1021/ol051707z
20.Chou, T.-C.; Yang, M.-S.; Lin, C.-T. J. Org. Chem. 1994, 59, 661–663.
doi:10.1021/jo00082a028
Supporting Information File 2
Crystallographic data of syn-bis-quinoxaline 16c.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-6-39-S2.pdf]
21.Khan, F. A.; Dash, J.; Sudheer, C.; Sahu, N.; Parasuraman, K.
J. Org. Chem. 2005, 70, 7565–7577. doi:10.1021/jo0507385
22.Khan, F. A.; Dash, J. J. Am. Chem. Soc. 2002, 124, 2424–2425.
doi:10.1021/ja017371f
23.Khan, F. A.; Prabhudas, B.; Dash, J.; Sahu, N. J. Am. Chem. Soc.
2000, 122, 9558–9559. doi:10.1021/ja001956c
Acknowledgements
24.Arotsky, J.; Butler, R.; Darby, A. C. J. Chem. Soc. C 1970, 1480–1485.
doi:10.1039/J39700001480
M.E. thanks the Research Corporation for Science Advance-
ment and the University of North Carolina at Charlotte for
financial support. M. G. gratefully acknowledges the financial
support of the Natural Sciences and Engineering Research
Council of Canada.
25.Heaton, M.; Hill, P.; Drakesmith, F. J. Fluorine Chem. 1997, 81,
133–138. doi:10.1016/S0022-1139(96)03517-8
26.Garcia, J. G.; Fronczek, F. R.; McLaughlin, M. L. Tetrahedron Lett.
1991, 32, 3289–3292. doi:10.1016/S0040-4039(00)92688-1
27.Garcia, J. G.; McLaughlin, M. L. Tetrahedron Lett. 1991, 32,
3293–3296. doi:10.1016/S0040-4039(00)92689-3
28.Mackenzie, K. J. Chem. Soc. 1964, 5710–5716.
doi:10.1039/JR9640005710
References
1. Chen, C.-W.; Whitlock, H. W., Jr. J. Am. Chem. Soc. 1978, 100,
29.Azizian, J.; Karimi, A. R.; Kazemizadeh, Z.; Mohammadi, A. A.;
Mohammadizadeh, M. R. J. Org. Chem. 2005, 70, 1471–1473.
doi:10.1021/jo0486692
4921–4922. doi:10.1021/ja00483a063
2. Zimmerman, S. C. Top. Curr. Chem. 1993, 165, 71–102.
doi:10.1007/BFb0111281
30.Yadav, J. S.; Reddy, B. V. S.; Rao, Y. G.; Narasaiah, A. V. Chem. Lett.
2008, 37, 348–349. doi:10.1246/cl.2008.348
3. Klärner, F.-G.; Kahlert, B. Acc. Chem. Res. 2003, 36, 919–932.
doi:10.1021/ar0200448
31.Sangshetti, J. N.; Kokare, N. D.; Shinde, D. B. Russ. J. Org. Chem.
2009, 45, 1116–1118. doi:10.1134/S1070428009070240
32.Zhao, Z.; Wisnoski, D.; Wolkenberg, S. E.; Leister, W. H.; Wang, Y.;
Lindsley, C. W. Tetrahedron Lett. 2004, 45, 4873–4876.
doi:10.1016/j.tetlet.2004.04.144
4. Harmata, M. Acc. Chem. Res. 2004, 37, 862–873.
doi:10.1021/ar030164v
5. Rowan, A. E.; Elemans, J. A. A. W.; Nolte, R. J. M. Acc. Chem. Res.
1999, 32, 995–1006. doi:10.1021/ar9702684
6. Katz, J. L.; Geller, B. J.; Foser, P. D. Chem. Commun. 2007,
1026–1028. doi:10.1039/b615336d
33.Waluk, J.; Grabowska, A.; Pakulstroka, B. J. Lumin. 1980, 21,
277–291. doi:10.1016/0022-2313(80)90007-1
7. Wei, T.-B.; Wei, W.; Cao, C.; Zhang, Y.-M.
34.Imes, K. K.; Ross, I. G.; Moomaw, W. R. J. Mol. Spectrosc. 1988, 132,
492–544. doi:10.1016/0022-2852(88)90343-8
Phosphorus, Sulfur Silicon Relat. Elem. 2008, 183, 1218–1228.
doi:10.1080/10426500701613154
35.Suga, K.; Kinoshita, M. Bull. Chem. Soc. Jpn. 1982, 55, 1695–1704.
doi:10.1246/bcsj.55.1695
8. Bhattacharya, S.; Tominaga, K.; Kimura, T.; Uno, H.; Komatsu, N.
Chem. Phys. Lett. 2007, 433, 395–402.
36.Baytekin, B.; Baytekin, H. T.; Schalley, C. Org. Biomol. Chem. 2006, 4,
2825–2841. doi:10.1039/b604265a
doi:10.1016/j.cplett.2006.11.039
9. Skibinski, M.; Gómez, R.; Lork, E.; Azov, V. A. Tetrahedron 2009, 65,
10348–10354. doi:10.1016/j.tet.2009.10.052
37.Hay, B. P.; Bryantsev, V. S. Chem. Commun. 2008, 2417–2428.
doi:10.1039/b800055g
10.Nishiuchi, T.; Kuwatani, Y.; Nishinaga, T.; Iyoda, M. Chem.–Eur. J.
2009, 15, 6838–6847. doi:10.1002/chem.200900623
11.Hay, B. P.; Custelcean, R. Cryst. Growth Des. 2009, 9, 2593–2545.
doi:10.1021/cg900308b
38.Quiñonero, D.; Garau, C.; Rotger, C.; Frontera, A.; Ballister, P.;
Costa, A.; Deyà, P. M. Angew. Chem., Int. Ed. 2002, 41, 3389–3392.
doi:10.1002/1521-3773(20020916)41:18<3389::AID-ANIE3389>3.0.CO
;2-S
12.Schottel, B. L.; Chifotides, H. T.; Dunbar, K. R. Chem. Soc. Rev. 2008,
37, 68–83. doi:10.1039/b614208g
39.Schaller, T.; Büchele, U. P.; Klärner, F.-G.; Bläser, D.; Boese, R.;
Brown, S. P.; Spiess, H. W.; Koziol, F.; Kussmann, J.; Ochsenfeld, C.
J. Am. Chem. Soc. 2007, 129, 1293–1303. doi:10.1021/ja0666351
40.Parac, M.; Etinski, M.; Peric, M.; Grimme, S. J. Chem. Theory Comput.
2005, 1, 1110–1118. doi:10.1021/ct050122n
13.Fujita, M.; Nagao, S.; Iida, M.; Ogata, K.; Ogura, K. J. Am. Chem. Soc.
1993, 115, 1574–1576. doi:10.1021/ja00057a052
14.Korenaga, T.; Kosaki, T.; Kawauchi, Y.; Ema, T.; Sakai, T.
J. Fluorine Chem. 2006, 127, 604–609.
doi:10.1016/j.jfluchem.2005.12.007
15.Korenaga, T.; Kawauchi, Y.; Kosaki, T.; Ema, T.; Sakai, T.
Bull. Chem. Soc. Jpn. 2005, 78, 2175–2179. doi:10.1246/bcsj.78.2175
Page 6 of 7
(page number not for citation purposes)

Beilstein Journal of Organic Chemistry 2010, 6, No. 39.
41.Shao, Y.; Molnar, L. F.; Jung, Y.; Kussmann, J.; Ochsenfeld, C.;
Brown, S. T.; Gilbert, A. T. B.; Slipchenko, L. V.; Levchenko, S. V.;
O’Neill, D. P.; DiStasio, R. C., Jr.; Lochan, R. A.; Wang, T.;
Beran, G. J. O.; Besley, N. A.; Herbert, J. M.; Lin, C. Y.;
Van Voorhis, T.; Chien, S. H.; Sodt, A.; Steele, R. P.; Rassolov, V. A.;
Maslen, P. E.; Korambath, P. P.; Adamson, R. D.; Austin, B.; Baker, J.;
Byrd, E. F. C.; Dachsel, H.; Doerksen, R. J.; Dreuw, A.; Dunietz, B. D.;
Dutoi, A. D.; Furlani, T. R.; Gwaltney, S. R.; Heyden, A.; Hirata, S.;
Hsu, C.-P.; Kedziora, G.; Khalliulin, R. Z.; Klunzinger, P.; Lee, A. M.;
Lee, M. S.; Liang, W. Z.; Lotan, I.; Nair, N.; Peters, B.; Proynov, E. I.;
Pieniazek, P. A.; Rhee, Y. M.; Ritchie, J.; Rosta, E.; Sherrill, C. D.;
Simmonett, A. C.; Subotnik, J. E.; Woodcock, H. L., III; Zhang, W.;
Bell, A. T.; Chakraborty, A. K.; Chipman, D. M.; Keil, F. J.; Warshel, A.;
Hehre, W. J.; Schaefer, H. F.; Kong, J.; Krylov, A. I.; Gill, P. M. W.;
Head-Gordon, M. Phys. Chem. Chem. Phys. 2006, 8, 3172–3191.
doi:10.1039/b517914a
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0), which
permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.6.39
Page 7 of 7
(page number not for citation purposes)