Generation and characterization of phenylsulfanylcarbene

Article abstract of DOI:10.1021/ol036524w

A photosensitive precursor (1) to phenylsulfanylcarbene 2 has been synthesized. Laser flash photolysis (308 nm) of 1 and chemical trapping studies of 2 are reported.

Full text of DOI:10.1021/ol036524w

ORGANIC
LETTERS
2004
Vol. 6, No. 5
815-818
Generation and Characterization of
Phenylsulfanylcarbene
Shannon E. Condon, Christophe Buron, Eric M. Tippmann, Courtney Tinner, and
Matthew S. Platz*
Department of Chemistry, The Ohio State UniVersity, 1118 Newman-Wolfrom,
100 W. 18th AVenue, Columbus, Ohio 43210
platz.1@osu.edu
Received December 30, 2003
ABSTRACT
A photosensitive precursor (1) to phenylsulfanylcarbene 2 has been synthesized. Laser flash photolysis (308 nm) of 1 and chemical trapping
studies of 2 are reported.
Carbenes bearing heteroatoms in the R position are of interest
as a result of intriguing electronic and inductive interactions
between the substituent and the carbene center.1 These
interactions are expected to dramatically influence the
lifetime, reactivity, and spectroscopy of the carbene. Fluo-
rophenylsulfanylcarbene was recently generated and char-
acterized in our group.2 Because halogen atoms can signifi-
cantly influence the chemical properties of carbenes,3 we
decided to focus our efforts on the parent phenylsulfanyl-
carbene in order to isolate the influence of the sulfur
substituent. In general, carbenes with a single heteroatom
substituent have not been widely studied by time-resolved
spectroscopic methods because of the absence of convenient
light-sensitive precursors. To our knowledge, the only
carbene of this class (H-C-X) studied to date is chlorocar-
bene.4 Herein, we report the synthesis and photochemistry
of a new precursor 1 of phenylsulfanylcarbene 2 and contrast
its properties with chlorocarbene and fluorophenylsulfanyl-
carbene.
The synthesis of precursor 1 is described in Scheme 1.
Dihydroindan 4 was prepared by Birch reduction of indan 3
as described in the literature.5 Addition of dibromocarbene
generated from bromoform and potassium tert-butoxide in
pentane allowed us to synthesize a 30/70 mixture of 5 and
6. Even at low temperature, it is difficult to control the
addition stoichiometry of the carbene to the diene. The
mixture of the two adducts was then stirred in THF with 1
molar equiv (relative to 5) of potassium tert-butoxide. Under
basic conditions, compound 5 decomposes rapidly, allowing
ready purification of 6. Transformation of 6 into 7 is achieved
by treatment with NBS/AIBN. After reduction to the mono
bromo derivative 8 with tri-n-butyltin hydride, bromine
lithium exchange was performed with tert-butyllithium at
low temperature, allowing us to introduce the phenylsulfanyl
group on the cyclopropane ring.
(1) See, for instance: Bourissou, D.; Guerret, O.; Gabbai, F. P.; Bertrand,
G. Chem. ReV. 2000, 100, 39 and references therein.
(2) Buron, C.; Tippmann, E. M.; Platz, M. S. J. Phys Chem. A 2004,
108, 1033.
(3) (a) Skell, P. S.; Garner, A. Y. J. Am. Chem. Soc. 1958, 78, 5430. (b)
Doering, W. v. E.; Henderson, W. A., Jr. J. Am. Chem. Soc. 1958, 80,
5274. (c) Moss, R. A. Carbene Chemistry. From Fleeting Intermediates to
Powerful Reagents; Bertrand, G., Ed.; FontisMedia S.A.: Lausanne, 2002;
p 57.
Photolysis (300 nm UV lamps) of a solution of 1 in neat
tetramethylethylene (TME) for 18 h yielded the correspond-
ing adduct 9 in 80% isolated yield. This demonstrates that
diene 1 is an efficient light-activated precursor of carbene 2
(4) Robert, M.; Toscano, J. P.; Platz, M. S.; Abbot, S. C. Kirchoff, M.
M.; Johnson, R. P. J. Phys. Chem. 1996, 100, 18426.
(5) Birch, A. J.; Walkerk, A. M. Aust. J. Chem. 1971, 24, 513.
10.1021/ol036524w CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/05/2004

Scheme 1a
Figure 1. Transient UV spectra produced by LFP (308 nm) of 1
in deoxygenated solvents with 7 mM pyridine. The spectra were
recorded immediately after the laser pulse over a window of 20
ns: (1) Freon-113; (2) cyclohexane; (3) tetrahydrofuran; (4)
benzene; (5) acetonitrile.
M-1 s-1 and an intercept of k0 ) 5.0 × 105 s-1 (Table 1) in
CF2ClCFCl2 (Freon-113). This corresponds to a lifetime (τ)
of phenylsulfanylcarbene 2 of 2 µs in deoxygenated Freon-
113. Analogous LFP experiments were performed in deoxy-
genated heptane and showed a small decrease in the carbene
lifetime and no change in the carbene reactivity toward
pyridine, relative to Freon-113.
In deoxygenated Freon-113 containing 7 mM of pyridine
it is possible to resolve the growth of the ylide absorption at
several concentrations of alkene trap (2,3-dimethyl-2-butene
or tetramethylethylene TME). A plot of the observed rate
constant of ylide formation versus the concentration of TME
(constant pyridine concentration) is linear, allowing us to
extract kTME ) 8.9 × 107 M-1 s-1 in Freon-113 (Table 1).
a (a) 90% (i) Na(s)/NH3(l), -50 °C, (ii) MeOH; (b) HCBr3,
t-BuOK, pentane, -78 °C, 41%; (c) NBS, AIBN cat., cyclohexane,
reflux, 3 h, 73%; (d) Bu3SnH, Et3B cat., O2, C6H6, rt, 24 h, 73%;
(e) 70% (i) t-BuLi 3 equiv, Et2O, -100 °C, 20 min, (ii) PhSSPh.
in solution. This result is consistent with the work of
Scho¨llkopf6 and Saquet,7 who generated 2 by treatment of
PhSCH2Cl with butyllithium or sodium hydride, respectively.
These groups reported that phenylsulfanylcarbene is ef-
ficiently intercepted by simple electron-rich alkenes.
Precursor 1 was studied by laser flash photolysis (LFP)
techniques in several solvents, and the transient UV absorp-
tion was recorded just after (<10 ns) the laser pulse. No
transient absorption was observed in the absence of pyridine
between 350 and 550 nm. This result is consistent with time
dependent density functional theoretical calculations (B3LYP/
6-31 g(d)) that predict only weak vertical absorptions at 317
and 302 nm for carbene 2.8
The transient UV spectra obtained in several solvents
containing 7 mM pyridine are presented in Figure 1. We
observed a broad absorption centered at 420 nm that is
attributed to the pyridine ylide 10 by analogy to numerous
other systems.9
Ylide 10 is formed in an exponential process after the laser
pulse, which can be analyzed to yield the observed rate
constant of ylide formation, kobs. A plot (Figure 2) of the
observed rate constant of ylide growth versus the concentra-
tion of pyridine is linear with a slope (kpyr) of 2.5 × 108
Figure 2. Plots of the observed rate constant of transient growth
at 420 nm versus concentration of trapping agent produced by LFP
(308 nm) of 1: (a) trapping with pyridine in deoxygenated Freon-
113; (b) trapping with pyridine in nondeoxygenated Freon-113; (c)
trapping with 2,3-dimethyl-2-butene in deoxygenated Freon-113
containing 7 mM pyridine.
(6) Scho¨llkopf, U.; Lehmann, G. J.; Paust, J.; Ha¨rtl, H.-D. Chem. Ber.
1964, 97, 7.
(7) Saquet, M. C. R. Acad. Sci. Paris: C 1972, 283.
816
Org. Lett., Vol. 6, No. 5, 2004

Table 1. Lifetime and Rate Constants of Carbene 2 with
2,3-Dimethyl-2-butene (TME) and Pyridine in Deoxygenated
Freon-113 Containing 7 mM Pyridine
PhSCHb
PhSCF2
ClCH4
τ (CF2ClCFCl2, Ar) ns
τ (CF2ClCFCl2, air) ns
2000
800
2000
<20
<20
a
a
k
k
k
PYR, M-1 s-1
TME, M-1 s-1
AC, M-1 s-1
2.5 × 108
8.9 × 107
3.0 × 107
-10.14
2.26
2.0 × 107
5.0 × 106 b
2.0 × 106
-10.74
a
E(HOMO) eV8,c
E(LUMO) eV8,c
-10.97
0.97
Figure 3. Optimized structure (B3LYP/6-31g(d)) of phenylsulfanyl
carbene 2. Calculated selected bond lengths: d(C8S7) ) 1.66 Å;
d(C8H14) ) 1.10 Å; angle at the carbene carbon S7C8H14 ) 103.8°.
2.09
a Lifetime too short to measure, but the bimolecular rate constant is likely
∼109 M-1 s-1; see text. b This work. c Orbital energies were calculated (HF
4-31G) as described by Rondan, N. G.; Houk, K. N.; Moss R.A, J. Am.
Chem. Soc. 1980, 102, 1770 to maintain consistency with earlier studies.
The carbene lone-pair is the HOMO of ClCH but is not the HOMO of
PhSCH and PhSCF. To retain consistency with earlier work, we will use
the energy of the carbene lone pair.
phenylsulfanylcarbene is also much less reactive toward
pyridine and TME than chlorocarbene (Table 1).
These observations can be understood with the aid of DFT
calculations.8 The optimized structure of phenylsulfanylcar-
bene 2 is shown in Figure 3. A natural population analysis
(NPA)12 of carbene 2 and of chlorocarbene calculated at the
same level of theory is shown in Table 2. This analysis
The carbene lifetime in aerated samples is shortened from
2.0 to 0.8 µs. This result is somewhat surprising, as singlet
carbenes typically do not react rapidly with oxygen. This
observation is not unprecedented, however, as Liu et al. have
previously reported such behavior with p-nitrophenylchlo-
rocarbene.10 At the B3LYP/6-31G(d) level of theory singlet
2 is predicted to be 17.7 kcal/mol more stable than the
corresponding triplet state of the carbene. Thus, it seems very
unlikely that a small equilibrium quantity of triplet 2 is
responsible for the observed reaction of phenylsulfanylcar-
bene with oxygen.
Phenylsulfanylcarbene 2 is found to be a much longer-
lived species than chlorocarbene, which has a lifetime of
less than 20 ns in Freon-113 at ambient temperature.4 This
very short lifetime prevented measurement of its absolute
rate constant of reaction with pyridine. It was possible to
determine that kTME/kPYR ) 1.01 in cyclohexane at ambient
temperature. The absolute value of kPYR was assumed to be
8.0 × 109 M-1 s-1 (average of the kPYR values of chlorom-
ethyl-, chlorobenzyl-, and dichlorocarbene).11 Therefore
Table 2. Natural Population Analysis (B3LYP/6-31g(d)) for
Phenylsulfanylcarbene, Fluorophenylsulfanylcarbene, and
Chlorocarbenea
PhS-CH
PhS-CF
HCCl
atom
no.
natural
atom
no.
natural
atom
no.
natural
charge
charge
charge
C1
C2
C3
C4
C5
C6
S7
C8*
H14
-0.23
-0.23
-0.22
-0.22
-0.22
-0.23
0.47
C1*
F2
S3
C4
C5
C6
C7
C8
C9
0.11
-0.33
0.33
-0.21
-0.23
-0.22
-0.22
-0.23
-0.23
C1*
Cl2
H3
-0.15
0.024
0.13
-0.54
0.18
a Asterisk denotes carbenic carbon.
(8) (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Lee, C.; Yang,
W.; Parr, R. G. Phys. ReV. B 1998, 37, 785. (c) Frisch, M. J.; Trucks, G.
W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.;
Zakrzewski, V. G.; Montgomery, J. A., Jr.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.;
Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.;
Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala,
P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari,
K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov,
J. V.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.7; Gaussian,
Inc.: Pittsburgh, PA, 1998. (d) Casida, M. E.; Jamorski, C.; Casida, K. C.;
Salahub, D. R. J. Chem. Phys. 1998, 108, 4439.
clearly shows that there is substantial π back-bonding from
sulfur to the carbene center. The C8-S7 bond length of 1.66
Å is much closer to that of a typical carbon-sulfur double
bond (1.60 Å) than to that of a single bond (1.82 Å).13 This
leads to greater charge separation in the case of phenylsul-
fanylcarbene relative to chlorocarbene. The charge on the
carbenic center is -0.54 (versus -0.15 for chlorocarbene).
This explains in a simple way why PhSCH reacts more
rapidly with methyl acrylate than does fluorophenylsulfa-
(9) Platz, M. S. In Carbene Chemistry. From Fleeting Intermediates to
Powerful Reagents; Bertrand, G., Ed.; FontisMedia S.A.: Lausanne, 2002;
p 27.
(10) Liu, M. T. H.; Bonneau, R.; Jefford, C. W. Chem. Commun. 1990,
21, 1482.
Am. Chem. Soc. 1989, 111, 5973. (e) Jackson, J. E.; Soundarajan, N.; White,
W.; Liu, M. T. H.; Bonneau, R. J.; Platz, M. S. J. Am. Chem. Soc. 1989,
111, 6874. (f) Chateauneuf, J. E.; Johnson, R. P.; Kirehoff, M. M. J. Am.
Chem. Soc. 1990, 112, 3217.
(11) (a) Liu, M. T. H.; Bonneau, R. J. J. Am. Chem. Soc. 1989, 111,
6873. (b) Jackson, J. E.; Soundarajan, N.; Platz, M. S.; Liu, M. T. H. J.
Am. Chem. Soc. 1988, 110, 5595. (c) Liu, M. T. H.; Bonneau, R. J. J. Phys.
Chem. 1989, 93, 7298. (d) Liu, M. T. H.; Bonneau, R. J.; Rayez, M. T. J.
(12) Reed, A. E.; Weinhold, F. A.; Curtiss, C. A. Chem. ReV. 1988, 88,
899.
(13) CRC Handbook of Chemistry and Physics; Lide, D. A.; CRC
Press: Boca Raton, FL, 2003.
Org. Lett., Vol. 6, No. 5, 2004
817

both sulfur-substituted carbenes are expected to be ambiphilic
because the electrophilic term is more favorable with TME,
but the nucleophilic term is more favorable with acrylate.
Table 3. HOMO-LUMO Separations of Three Carbenes with
Tetramethylethylene and Methylacrylate in eV
In summary, we have synthesized a new light-sensitive
precursor of phenylsulfanylcarbene 2. Continuous photolysis
of 1 in the presence of tetramethylethylene (TME) releases
indan and carbene 2 as evidenced by the formation of the
anticipated carbene-TME cyclopropane adduct. Laser flash
photolysis (LFP) of precursor 1 fails to produce an observable
transient spectrum of 2, but LFP in the presence of pyridine
produces an easily detected spectrum of the ylide. The
lifetime and reactivity of carbene 2 was determined by the
pyridine ylide technique. Phenylsulfanylcarbene is less
reactive than chlorocarbene and is found to be ambiphilic.
This is in agreement with a frontier orbital analysis as
previously formulated by Moss.14
ClCH
PhSCH
PhSCF
p/π
π*/σ
p/π
π*/σ
p/π
π*/σ
TME
acrylate
9.24
11.69
13.24
11.77
10.53
12.98
12.41
10.44
10.36
12.81
13.01
11.54
nylcarbene, which has a charge of +0.11 on the carbene
carbon according to an NPA analysis.
Although the NPA analysis explains why PhSCH is more
nucleophilic than PhSCF, it does not explain why it is also
more electrophilic than the fluoro analogue. Moss14 has
demonstrated that singlet carbene reactivities are best
understood on the basis of frontier molecular orbital (FMO)
interactions. Thus, the HOMO-LUMO orbital energies of
chloro-, fluorophenylsulfanyl-, and phenylsulfanylcarbene
were calculated (HF/6-31G). As stated by Moss,14b “What
determines the carbene expressed philicity is whether, in the
transition state, it is the LUMOcarbene-HOMOalkene (p/π)
Acknowledgment. Support of this work by the National
Science Foundation and the Ohio Supercomputer Center is
gratefully acknowledged. E.M.T. gratefully acknowledges a
Graduate Assistantship in the Area of National Needs
Fellowship. The authors are indebted to Professor R. A. Moss
for useful discussions and thank Ms. Jin Liu for the
calculations of carbene orbital energies at the 4-31G level.
electrophilic (E) orbital interaction or the HOMOcarbene
LUMOalkene (σ/π*) nucleophilic (N) interaction that is
dominant.” The relevant data can be found in Table 3.
-
The data predict that chlorocarbene is electrophilic because
the p/π energy separation LUMOcarbene-HOMOalkene (E) term
Supporting Information Available: Optimized geom-
etry, energy, zero-point correction, natural population analy-
sis, IR frequencies, and TD-DFT of 2 and experimental
details for synthesis of compounds 1 and 3-9. This material
is available free of charge via the Internet at http://pubs.acs.org.
is smaller and more favorable than the HOMOcarbene
-
LUMOalkene (N) term with both TME and acrylate. However,
(14) (a) Moss, R. A. Acc. Chem. Res. 1980, 13, 58. (b) Moss, R. A.
Acc. Chem. Res. 1989, 22, 15.
OL036524W
818
Org. Lett., Vol. 6, No. 5, 2004