Regiochemical substituent switching of spin states in aryl(trifluoromethyl) carbenes

Article abstract of DOI:10.1021/ja209613u

Although aryl(trifluoromethyl)diazirines have achieved great popularity in photoaffinity labeling applications, the properties of the corresponding carbenes have not been as widely explored. Here, low-temperature matrix-isolation spectroscopy and reactivi

Full text of DOI:10.1021/ja209613u

COMMUNICATION
pubs.acs.org/JACS
Regiochemical Substituent Switching of Spin States in
Aryl(trifluoromethyl)carbenes
Myoung-Geun Song and Robert S. Sheridan*
Department of Chemistry, University of Nevada, Reno, Nevada 89557, United States
S Supporting Information
b
Scheme 1
ABSTRACT: Although aryl(trifluoromethyl)diazirines have
achieved great popularity in photoaffinity labeling applications,
the properties of the corresponding carbenes have not been
as widely explored. Here, low-temperature matrix-isolation
spectroscopy and reactivity studies indicate that in contrast to
m-methoxyphenyl(trifluoromethyl)carbene and most known
aryl(CF3)carbenes, the para isomer is a ground-state singlet
rather than triplet. DFT calculations support these results as
well as the notion that the p-CH3O group stabilizes the singlet
carbene via resonance. These results may have relevance to the
wide range of substituted aryl(CF3)diazirines in photoaffinity
applications.
ryl(trifluoromethyl)diazirines enjoy great popularity in
A
photoaffinity labeling applications.1 Despite their widespread
use, however, significant gaps exist in the understanding of the
chemistry and electronics of the corresponding aryl(trifluoro-
methyl)carbenes.2 In fact, the fundamental issue of ground-state
multiplicity in these species has not been examined extensively
either experimentally or theoretically. Electron paramagnetic reso-
nance (EPR) spectra reported for phenyl(trifluoromethyl)-3 and
p-tolyl(trifluoromethyl)carbene4 at 77 K indicate that the triplets are
either the ground states or are nearly degenerate with singlet ground
states. Solution trapping rates determined by laser flash photolysis
allowed Platz and co-workers to estimate that the singlet tolyl-
(CF3)carbene lies 0.5ꢀ1.5 kcal/mol above the triplet.4 More
recently, it has been shown both experimentally and theoretically
that the singletꢀtriplet energy gap in 4,40-biphenyl(CF3)carbene
depends on the polarity of the medium, with the singlet being the
ground state in polar solvents.5 Sander’s group6 and ours7 have
reported that phenyl(trifluoromethyl)carbene reacts readily with
O2 and H2, respectively, at cryogenic temperatures; both reactions
are characteristic of ground-state triplets. On the other hand, our
group has recently shown that 2-benzothienyl(CF3)carbene is a
ground-state singlet.8 Hence, how the carbene spin states are
influenced by the wide array of substituents utilized in photo-
affinity applications is an important but open question.1 Herein we
report experimental and theoretical studies demonstrating that the
ground-state multiplicity of aryl(trifluoromethyl)carbenes may be
tuned selectively via surprisingly modest substitution changes.
The known9,10 m-methoxyphenyldiazirine 1 was synthesized
from the corresponding ketone by a slight modification of litera-
ture procedures. Irradiation of 1 in a N2 matrix at 7 K with
366 nm light11 converted the diazirine cleanly to carbene 2
(Scheme 1). The IR spectra of 2 fit density functional theory
(DFT) predictions at the B3LYP/6-31+G(d,p) level12 reason-
ably well, though it was not possible to distinguish between the
four possible conformations of the carbene or between the triplet
and singlet states on this basis. The UVꢀvis spectrum of 2,
however, exhibited considerable structure, as is typically ob-
served for triplet arylcarbenes (Figure 1).13 In particular, time-
dependent (TD) B3LYP calculations12 for triplet 2 (especially
the syn,syn lowest-energy conformer) paralleled the experimen-
tal UVꢀvis absorptions; the calculated spectrum for singlet 2 did
not match that observed.
The carbene was stable under further irradiation, regardless of
wavelength, although minor changes in the IR and UVꢀvis spectra
could be detected, possibly signaling conformational changes. EPR
spectra10 generated by irradiation of 1 in a perfluoro-2-n-butylte-
trahydrofuran glass at ca. 90 K displayed typical triplet carbene
signals,4 with |D/hc| and |E/hc| values of 0.519 and 0.030 cmꢀ1
,
respectively. A second smaller set of signals corresponding to
|D/hc| = 0.532 cmꢀ1 and |E/hc| = 0.031 cmꢀ1 were also detected,
presumably arising from a different carbene conformer. These
values are similar to those reported for triplet p-tolyl(trifluoro-
methyl)carbene (|D/hc| = 0.5215 cmꢀ1, |E/hc| = 0.0305 cmꢀ1 4
)
and phenyl(trifluoromethyl)carbene (|D/hc| = 0.5098 cmꢀ1
,
|E/hc| = 0.0249 cmꢀ1).3
The reactivity of 2 confirmed its triplet multiplicity. Numerous
studies6 have shown that triplet carbenes react rapidly with O2 at
low temperatures, whereas singlet carbenes are unreactive under
the same conditions. Warming a 0.5% O2-doped nitrogen matrix
containing 2 to 30 K readily converted the carbene primarily to
carbonyl oxide 3, which was identified through comparison of the
product IR bands to those from B3LYP calculations.10 A strong,
Received: October 12, 2011
Published: November 08, 2011
r
2011 American Chemical Society
19688
dx.doi.org/10.1021/ja209613u J. Am. Chem. Soc. 2011, 133, 19688–19690
|

Journal of the American Chemical Society
COMMUNICATION
Figure 1. UVꢀvis spectra of m-diazirine 1 in N2 at 7 K before (a, in blue)
and after (b, in black) irradiation at 366 nm for ca. 12 h. (c) TD B3LYP-
predicted transitions for the syn,syn conformations of singlet (black) and
triplet (red) m-carbene 2. Calculated f value scales are shown at the right.
Figure 2. UVꢀvis spectra of p-diazirine 6 in N2 at 7 K before (a, in blue)
and after (b, in black) irradiation at 366 nm for ca. 12 h. (c) TD B3LYP-
predicted transitions for the syn conformations of singlet (black) and
triplet (red) p-carbene 7. Calculated f value scales are shown at the right.
very broad absorption was observed with a maximum at ca.
400 nm in the UVꢀvis spectrum, similar to that reported for the
corresponding phenyl(trifluoromethyl)carbeneꢀO2 trapping
product.6 As demonstrated in analogous systems, subsequent
irradiation of the matrix at 546 nm transformed 3 to the corre-
sponding dioxirane 4. Previous work in our group7 has shown that a
variety of triplet carbenes (but not singlets) add H2 at very low
temperatures, presumably via a tunneling-assisted H-abstraction/
recombination process. As with triplet phenyl(trifluoromethyl)-
carbene,7 annealing in an Ar matrix containing 2% H2 to 25 K con-
verted carbene 2 to hydrogenated product 5. However, in contrast
to singlet carbenes, 2 did not appear to react with HCl in doped
matrices up to the matrix degradation temperatures of ca. 35 K.
The behavior of the corresponding p-methoxycarbene was
dramatically different. The known9,10 diazirine precursor 6 was
synthesized in similar fashion to the meta isomer. Irradiation of 6
isolated in a N2 matrix at 7 K using 366 nm light converted it to
carbene 7. The IR spectrum of 7 was similar to that calculated at
the B3LYP level for the singlet carbene, and the fit to that
predicted for the triplet carbene conformers was marginally less
satisfactory.10 The UVꢀvis spectrum of the carbene was domi-
nated by an intense absorption at 330 nm, as predicted by TD
B3LYP calculations for singlet carbene (289 nm, f = 0.51;
Figure 2). Multiple transitions between 428 and 290 nm pre-
dicted for triplet 7 were not observed. Moreover, 7 showed a
broad absorption at 820 nm (TD 972 nm), characteristic of σꢀp
transitions of singlet carbenes.10,14
Finally, irradiation of 6 under the same low-temperature per-
fluoro-2-n-butyltetrahydrofuran glass conditions as for the meta
isomer 1 gave no triplet EPR signals.
Calculations12 support the experimental indications that
m-methoxycarbene 2 is a ground-state triplet, whereas the para
isomer 7 is a singlet. Others have shown that B3LYP calculations
afford satisfactory approximations to arylcarbene singletꢀtriplet
(ST) energy gaps.15 Comparisons to results obtained using higher
levels of theory as well as from experiments indicate, however,
that the DFT methodology tends to overestimate the stability of
triplet carbenes relative to singlets by 1ꢀ3 kcal/mol. B3LYP/
6-31+G(d,p) calculations on the four planar conformations of
m-carbene 2 gave ST energy gaps (positive values signifying
triplet lowest) of 3.7ꢀ4.4 kcal/mol. A calculated overstabilization of
the triplet carbene15 by as much as 3 kcal/mol would still predict a
triplet ground state. In contrast, the calculations predicted ST energy
gaps of ꢀ0.4 and ꢀ0.7 kcal/mol for the syn and anti conformers,
respectively, of p-carbene 7 (or, ca. ꢀ2.4 and ꢀ2.7 kcal/mol after
correction for ca. 2 kcal/mol overstabilization of the triplet15).
Although lone-pair π donation is well-known to stabilize
singlet carbenes,14 it is not obvious that interaction with the
p-methoxy group in 7 would be sufficient to lower the singlet below
the triplet. Calculations have predicted that the triplet and singlet
states are approximately degenerate in the corresponding parent
carbene, p-methoxyphenylcarbene.15b However, we have shown
recently that in comparison with H, CF3 groups stabilize singlet
carbenes relative to triplet carbenes by a small but systematic
amount.16 We have described calculational evidence that the
strongly electron-withdrawing trifluoromethyl group causes rehy-
bridization of the adjacent carbenic lone pair through a Bent’s
rule effect, thus selectively stabilizing singlet carbenes relative to
triplets. For example, phenyl(trifluoromethyl)carbene has an ST
energy gap of 4.0 kcal/mol (vs 5.4 kcal/mol for phenylcarbene) at the
B3LYP/6-31+G(d,p) level.16 Thus, the inherently small ST gap in
The low-temperature reactivity of 7 also was consistent with
singlet rather than triplet multiplicity. Regardless of concentra-
tion, 7 did not react on warming in O2-doped matrices up to their
degradation temperatures at ca. 35 K. Similarly, no reaction
with H2 could be observed under conditions where triplet
carbenes react. However, warming singlet 7 in HCl-doped
matrices (0.5% in N2, 32 K) caused the IR bands of 7 to disappear
and those of the corresponding trapping product 8 to grow.10
19689
dx.doi.org/10.1021/ja209613u |J. Am. Chem. Soc. 2011, 133, 19688–19690

Journal of the American Chemical Society
COMMUNICATION
Scheme 2. Isodesmotic Comparison at the B3LYP/
6-31+G(d,p) Level (Energies in kcal/mol)
of this research and to the National Science Foundation
(CHE-0809216 and CHE-0840429 for the EPR spectrometer).
’ REFERENCES
(1) For example, see: (a) Hashimoto, M.; Hatanaka, Y. Eur. J. Org.
Chem. 2008, 2513. (b) Blencowe, A.; Hayes, W. Soft Matter 2005, 1, 178.
(c) Hatanaka, Y.; Sadakane, Y. Curr. Top. Med. Chem. 2002, 2, 271.
(2) Brahms, D. L. S.; Dailey, W. P. Chem. Rev. 1996, 96, 1585.
(3) Wasserman, E.; Barash, L.; Yager, W. A. J. Am. Chem. Soc. 1965,
87, 4974.
(4) Admasu, A.; Gudmundsdottir, A. D.; Platz, M. S.; Watt, D. S.;
Kwiatkowski, S.; Crocker, P. J. J. Chem. Soc., Perkin Trans. 2 1998, 1093.
(5) (a) Wang, J.; Kubicki, J.; Gustafson, T. L.; Platz, M. S. J. Am.
Chem. Soc. 2008, 130, 2304. (b) Wang, J.; Kubicki, J.; Peng, H.; Platz,
M. S. J. Am. Chem. Soc. 2008, 130, 6604.
phenyl(trifluoromethyl)carbene enables the observed substituent
switching of the multiplicity in 2 versus 7.
(6) Sander, W. J. Org. Chem. 1988, 53, 121.
Others have shown the utility of isodesmotic calculations in
probing the relative effects of carbene substituents on the energies
of singlet versus triplet carbenes.17 Such comparisons between
m-methoxycarbene 2 and phenyl(CF3)carbene (Scheme 2) suggest
a negligible influence of the m-CH3O group on either the triplet
or singlet energies. In contrast, although the p-CH3O group
stabilizes triplet 7 relative to the phenylcarbene by a small
amount, singlet 7 is stabilized considerably. As noted similarly
by Giese and Hadad in studies of a variety of related singlet
phenylcarbenes,15b the computed geometries and natural bond
orbital (NBO) charge distributions of 2 and 7 show negligible
differences related to conjugation. However, the importance of
resonance structure 7a in the singlet carbene is reflected clearly in
the very different barriers for Arꢀcarbene and ArꢀO rotation
predicted for the para and meta isomers. Both rotational barriers
were calculated to be significantly larger for the para singlet
carbene 7 (ca. 21 and 6 kcal/mol, respectively) than for the
corresponding meta singlet 2 (ca. 14 and 3 kcal/mol).18
In summary, we have shown that appending a p-methoxy
group to phenyl(trifluoromethyl)carbene switches its ground
state from a triplet to a singlet. In contrast, the m-methoxy
isomer, where direct resonance interaction between oxygen and
the singlet carbene is precluded, is a triplet. It is the inherently
narrow ST energy gap in phenyl(trifluoromethyl)carbene that
allows the ground-state multiplicity to be toggled by substituent
effects.16 Moreover, the photochemical stability of CF3-substi-
tuted carbenes at low temperatures, relative to other substituted
phenylcarbenes,13 makes these systems particularly useful for
probing substituent effects.19 These results may have some
relevance in fine-tuning the properties of aryl(CF3)carbenes in
photoaffinity applications.
(7) Zuev, P. S.; Sheridan, R. S. J. Am. Chem. Soc. 2001, 123, 12434.
(8) Wang, J.; Sheridan, R. S. Org. Lett. 2007, 9, 3177.
(9) Hatanaka, Y.; Hashimoto, M.; Kurihara, H.; Nakayama, H.;
Kanaoka, Y. J. Org. Chem. 1994, 59, 383.
(10) See the Supporting Information for experimental details as well
as additional IR, UVꢀvis, and EPR spectra.
(11) For a general description of the matrix isolation instrumenta-
tion, see: Sheridan, R. S.; Zuev, P. S. J. Am. Chem. Soc. 2004, 126, 12220
and references cited therein. See the Supporting Information for further
matrix deposition and irradiation details.
(12) All structures were fully optimized by analytical gradient
methods using Gaussian 03 (Frisch, M. J.; et al. Gaussian 03, revision
E.01; Gaussian, Inc.: Wallingford, CT, 2004). All energies were cor-
rected for zero-point energy differences (ZPVE) (unscaled). See the
Supporting Information for calculational details and results.
(13) (a) Sander, W. W.; Bucher, G.; Wierlacher, S. Chem. Rev. 1993,
93, 1583 and references cited therein. (b) Matzinger, S.; Bally, T. J. Phys.
Chem. A 2000, 104, 3544.
(14) Sheridan, R. S. J. Phys. Org. Chem. 2010, 23, 326–332.
(15) (a) Woodcock, D. H. L.; Moran, D.; Brooks, B. R.; Schleyer,
P. v. R.; Schaefer, H. F., III. J. Am. Chem. Soc. 2007, 129, 3763. See
references cited therein for a discussion of the general tendency of DFT
to overestimate the stability of triplet states. (b) Geise, C. M.; Hadad,
C. M. J. Org. Chem. 2000, 65, 8348.
(16) Song, M.-G.; Sheridan, R. S. J. Phys. Org. Chem. 2011, 24, 889.
(17) (a) Nemirowski, A.; Schreiner, P. R. J. Org. Chem. 2007,
72, 9533. (b) Gronert, S.; Keeffe, J. R.; More O’Ferrall, R. A. J. Am.
Chem. Soc. 2011, 133, 3381 and references cited therein.
(18) The corresponding CH3 and CF3 rotational barriers for triplet
2 and 7 range from 2.3 to 3.5 kcal/mol.
(19) A referee noted the interesting differences between the UVꢀvis
spectra predicted by TD DFT for the meta and para triplet carbene
isomers shown in Figures 1 and 2. As described in depth by Matzinger
and Bally (ref 13b), the electronic excited states of triplet phenylcar-
benes are particularly mixed configurationally and complex to interpret.
As illustrated in the TD DFT molecular orbital mixing breakdowns
listed for triplet carbenes 2 and 7 in the Supporting Information,
the methoxy group adds yet another level of complexity that is
difficult to analyze through simple orbital schemes. We are continu-
ing to investigate the effect of substituents on the spectra of triplet
and singlet aryl(trifluoromethyl)carbenes.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details, spectra,
b
results of DFT calculations, and complete ref 12. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
rss@unr.edu
’ ACKNOWLEDGMENT
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for partial support
19690
dx.doi.org/10.1021/ja209613u |J. Am. Chem. Soc. 2011, 133, 19688–19690