β-Halo-α,β-unsaturated γ-sultones

Article abstract of DOI:10.1021/jo071085q

(Chemical Equation Presented) The reaction of β-iodo-α,β- unsaturated γ-sultones (i.e., 4-halo-1,2-oxathiole 2,2-dioxides) in aprotic polar solvents such as DMSO or acetone, with 'soft' nucleophiles such as iodide or thioacetate, yields an allenesulfonate

Full text of DOI:10.1021/jo071085q

â-Halo-r,â-unsaturated γ-Sultones
Samuel Braverman,* Tatiana Pechenick-Azizi, Dan T. Major, and Milon Sprecher
Department of Chemistry, Bar-Ilan UniVersity, Ramat-Gan 52900, Israel
braVers@mail.biu.ac.il
ReceiVed May 22, 2007
The reaction of â-iodo-R,â-unsaturated γ-sultones (i.e., 4-halo-1,2-oxathiole 2,2-dioxides) in aprotic polar
solvents such as DMSO or acetone, with ‘soft’ nucleophiles such as iodide or thioacetate, yields an
allenesulfonate by a very facile halophilic ring-opening E2-elimination. The ‘harder’ nucleophile, azide
ion, reacts under the same conditions to yield the corresponding â-azido-R,â-unsaturated γ-sultone (i.e.,
4-azido-1,2-oxathiole 2,2-dioxide), displacing the â-halide by an addition-elimination mechanism. In
contrast, in the hydroxylic solvent CD3OD at ambient temperature, various nucleophiles yield neither of
the above-mentioned products, but catalyze a rapid replacement of the CR-H by deuterium. Factors
underlying this intriguing rapid exchange are proposed. Interestingly, the â-bromo analogue exhibits
similar reactivity except for the halophilic ring-opening. Calculations indicate the relative importance of
the â-halogen and the S-O(-C) bonds in enhancing the acidity of the H-CR-S(O)2- grouping.
Introduction
γ-sultones, and particularly of â-halo-substituted representatives
of this family. We therefore embarked on a systematic study of
their chemistry, and herein, we report some intriguing findings.
Our initial expectation was that a variety of â-substituents
might be introduced into the structure by nucleophilic displace-
ment of the â-halogen of the â-bromo- or â-iodo-R,â-unsatur-
ated γ-sultone via an addition-elimination mechanism (Scheme
2). Consequently, our investigations commenced in that direc-
tion. In the event, it was discovered that the loci and products
of the reactions of the title compounds with nucleophiles were
highly sensitive to the solvent and to the nature of the
nucleophile.1f,g
In a recent and in previous communications, we reported on
methods for the preparation of R,â-unsaturated γ-sultines and
their â-bromo (1, X ) Br) and â-iodo (2, X ) I) derivatives
from allenesulfinate (3) and allenethiosulfinate (4) esters.1a,c-g
These esters were accessed via [2,3]-sigmatropic rearrangements
of dipropargyl sulfoxylates (5)1a,c-g and of the novel propar-
gyloxy allyl disulfides (6),1b respectively (Scheme 1).
The R,â-unsaturated γ-sultines are of interest, inter alia,
because of their possible biological activity, since they are sulfur
analogues of γ-butenolides.2 The same may be said of R,â-
unsaturated γ-sultones (7), which are available by oxidation of
the corresponding sultines (Scheme 2). Though there is recent
chemical literature on γ-sultones in general,3 there is a relative
dearth of information on the reactivity of R,â-unsaturated
Results and Discussion
The sultones used in this investigation were obtained by
oxidation of the corresponding sultines with m-chloroperbenzoic
acid in CH2Cl2 solution. The sultines were prepared by one of
the paths reported previously (Scheme 1).1a, c-g The substitution
pattern of the various compounds and their designations are
shown in Table 1. The sultones listed in Table 2 were reacted
in d6-DMSO or in d6-acetone solution with the specified
nucleophiles under the stated conditions. The reactions were
* Corresponding author. Fax, 972-3-7384053.
(1) (a) Braverman, S.; Pechenick, T.; Sprecher, M. J. Org. Chem. 2006,
71, 2147-2150. (b) Braverman, S.; Pechenick, T.; Gottlieb, H. E.; Sprecher,
M. Tetrahedron Lett. 2004, 45, 8235-8238. (c) Braverman, S.; Reisman,
D. J. Am. Chem. Soc. 1977, 99, 605-607. (d) Braverman, S.; Reisman, D.
Tetrahedron Lett. 1977, 20, 1753-1756. (e) Braverman, S.; Duar, Y. J.
Am. Chem. Soc. 1983, 105, 1061-1063.(f) Braverman, S.; Pechenick-Azizi,
T.; Sprecher, M. 1st European Chemistry Congress, Budapest, Hungary,
Aug. 27-31, 2006, abstract, p 308. (g) Braverman, S.; Pechenick-Azizi,
T.; Sprecher, M. 18th Conference on Physical Organic Chemistry, Warsaw,
Poland, Aug. 20-25, 2006, abstract, p 39.
(3) For example, Enders, D.; Harnying, W.; Raabe, G. Synthesis 2004,
590-594.
(2) Ma, S.; Shi, Z. J. Org. Chem. 1998, 63, 6387-6389.
10.1021/jo071085q CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/04/2007
6824
J. Org. Chem. 2007, 72, 6824-6831

â-Halo-R,â-unsaturated γ-Sultones
SCHEME 1
SCHEME 2
Thus, the four â-halo-R,â-unsaturated γ-sultones, 7b, 7c, 8a,
and 8b, were each quantitatively converted to the corresponding
â-azido-R,â-unsaturated γ-sultones 10b, 10c, 10a, and 10b,
respectively, under the conditions and in the times stated. The
fact that the bromo sultone 7b reacted about twice as fast as
the iodo sultone 8b (t1/2 15 vs 29 min) suggests that the reaction
proceeds via an addition-elimination mechanism in which the
first step is rate-determining. In the reaction of the â-iodo
γ-sultone 8c, dimethyl substituted on C-γ, the halophilic
â-elimination competed with the nucleophilic displacement
(Table 3, lines 5). Relating to the rate of displacement only,
the bromo compound 7c reacted approximately 120 times as
fast as the corresponding iodo compound 8c, in agreement with
the aforementioned conclusion as to mechanism. Steric hin-
drance to approach to the â-carbon is presumably responsible
for the fact that nucleophilic displacement on the γ,γ-dimethyl
sultone is significantly slower than on the γ-monoalkyl sultones.
Reaction of â-Halo-r,â-unsaturated γ-Sultones with Nu-
cleophiles in Methanol. Our most surprising finding, at first
sight, was when we reacted the iodo and the bromo sultones
with nucleophiles in CD3OD solution at ambient temperature.
Under these conditions, neither carbophilic nucleophilic dis-
placement of the halide nor halophilic â-elimination occurred
(except in one case; Table 4, line 16). Rather, a complete
exchange of the R-hydrogen of the sultones for deuterium took
place. In some cases, this exchange was extremely rapid, though
the nucleophiles involved are very weak bases. The data are
summarized in Table 4. Be it noted that the γ-phenyl sultone,
8e, exchanged its R-hydrogen, but not its benzylic hydrogen,
though it is also vinylogously R to the sulfonate function (line
17). In control experiments (CD3OD, NaN3 2 equiv, room
temperature), it was found that neither the sultine 2b (corre-
sponding to sultone 8b), the sodium allenesulfonate salts (9),
nor divinyl sulfone suffered H-D exchange.
It is well-known, and rationalized in terms of solvation and
hydrogen bonding, that nucleophilicity is significantly attenuated
in going from an aprotic solvent to a hydroxylic one. However,
the same is true for basicity, which, in its kinetic aspect relevant
in the current context, may be viewed as nucleophilic attack on
H.6 The drastic change of reaction type observed in the present
context was therefore unexpected. Implicit in the foregoing
statements is the assumption that the observed H-D exchange
with the solvent proceeds in a simple and direct manner by
proton/deuteron transfers, starting with deprotonation (carbanion
formation) at the R-carbon of the sultone by the nucleophile
() base) in question (Scheme 4). However, a priori, two other
pathways may be considered for the exchange. One possibility
is a Michael type addition of the nucleophile to the â-carbon,
producing an R-carbanion which takes up a deuteron from the
solvent and then yields its proton to a base, thereby reverting
TABLE 1. Designation of γ-substituents of 1 (X ) Br), 2 (X ) I),
3, 7 (X ) Br), 8 (X ) I), 9, 10 (Y ) N3), and 11 (X ) H)
R1
R2
a
b
c
d
e
H
H
CH3
H
CH3
CH3
-(CH2)5-
H
Ph
monitored by NMR spectroscopy and, unless otherwise stated,
were allowed to proceed until the starting sultone was com-
pletely converted to product. In cases in which a defined product
was obtained (lines 1-8), the only product formed (and isolated)
was the corresponding allenesulfonate salt (9), resulting from a
ring-opening halophilic 1,2-elimination reaction (Scheme 2).
Such reaction was observed only with â-iodo sultones and not
with a â-bromo sultone (line 13).
Such elimination reactions are well-known,4 and these
particular examples are noteworthy only for the mild conditions
under which they occur. Presumably, the combination of the
preexistence of the anti-periplanar location of the vicinal iodide
and sulfonate ester functions, the propensity of the sulfonate
anion to act as a leaving group, and the release of ring strain
results in a facile E2-type elimination involving a ‘soft-soft’
interaction. The formation of I2 in this reaction is evidenced by
the appearance of iodine color which is discharged upon addition
of Na2S2O3 solution. The elimination is very rapid in the case
of sultone 8e (Table 2, lines 6 and 7), in which the γ-carbon is
benzylic, and is faster in the cases of 8c (line 4) and 8d (line 5)
in which the γ-carbon is tertiary, than in the case of 8b (lines
1-3), in which it is secondary. However, such a comparison
of rates must take into account that, in the reactions of the three
mentioned γ-alkyl-substituted sultones with NaI, the presence
of 25 equiv of the latter were found necessary to drive (and
-
‘pull’, by I3 formation) the elimination to completion. This
indicated that the halophilic elimination was reversible, a
conclusion which was confirmed by the finding that the addition
of I2 (25 equiv) + NaI (25 equiv) to a DMSO solution of the
3,3-dimethylallenesulfonate salt 9c at ambient temperature
converted it quantitatively to the iodo sultone 8c.
The nucleophilic displacement of the â-halogen, a carbophilic
reaction, was achieved in d6-DMSO at ambient temperature only
with the ‘harder’ nucleophile, azide ion.5 The reaction is
illustrated in Scheme 3, and the findings are summarized in
Table 3.
(6) (a) Pearson, R. G.; Dillon, R. L. J. Am. Chem. Soc. 1953, 75, 2439-
2443.(b) Gordon, A. J.; Ford, R. A. A Chemist’s Companion. A. Handbook
of Practical Data, Techniques, and References; Wiley-Interscince: New
York, 1972. (c) Bordwell, F. G.; Imes, R. H.; Steiner, E. C. J. Am. Chem.
Soc. 1967, 89, 3905-3906.
(4) Zefirov, N. S.; Makhon’kov, D. I. Chem. ReV. 1982, 82, 615-624.
(5) (a) Tse-Lok Ho Chem. ReV. 1975, 75, 1-20. (b) AdVanced Organic
Chemistry, Part A. Structure and Mechanisms, 4th ed.; Carey, F. A.,
Sundberg, R. J., Eds.; Kluwer Academic, New York, 2000; Chapter 5.
J. Org. Chem, Vol. 72, No. 18, 2007 6825

Braverman et al.
TABLE 2. Conversion of â-Iodo γ-Sultones (8)a to Allenesulfonates (9)
sultone
nucleophile
T, °C; solvent
time
2 days
product
1
2
3
4
8b
8b
8b
8c
NaI 25 equiv
NaCN 2 equiv
CH3C(O)SK 2 equiv
NaI 25 equiv
56 °C; DMSO
RT; DMSO
RT; DMSO
RT; DMSO
RT; acetone
RT; DMSO
RT; acetone
RT; DMSO
RT; acetone
RT; DMSO
RT; DMSO
RT; DMSO
RT; DMSO
RT; DMSO
RT; DMSO
RT; DMSO
9b
9b
9b
9cb
∼2 h
1 h
3.5 h
e3.5 h
3 h
5
6
8d
8e
NaI 25 equiv
NaI 3 equiv
9db
9eb
9e
e3 h
e1 min
e1 min
e1 min
1h 20 min
after18 h
after 2 h
<3 h
7
8
9
10
11
12
13
8e
8e
8b
8b
8b
8c
7c
NaBr 5 equiv
NaN3 2 equiv
KSCN 2 equiv
NaNO2 2 equiv
Na2S 1 equiv
KSCN 2 equiv
NaI 25 equiv
9e, subsequent decomposition
no reaction
no reaction
decomposition
no reaction
decomposition
after 5 days
a The sultone concentration was ∼0.05 ( 0.01 M. b The pure sodium allenesulfonate salts precipitated from the acetone solutions in quantitative yield.
SCHEME 3
SCHEME 6
TABLE 3. Reaction of the â-Halo γ-Sultonesa with NaN3 (2 equiv)
in DMSO
â-halo
γ-sultone
time
(RT)
product
(% yield)b
1
2
3
4
5
7b
7c
8a
8b
8c
1 h
4 h
1 h
2 h
10b (100)
10c (100)
10a (100)
10b (100)
10c (61) + 9c (27)
+ 8c (12)
(i.e., an SN1 reaction), but no such solvolysis product is
observed. Furthermore, assuming reasonably that in such a
mechanism the ionization step would be rate-determining, the
higher reactivity of the bromo derivatives as compared to the
iodo ones, as well as the lack of exchange at ambient
temperature of the R,â-unsaturated-γ,γ-dimethyl γ-sultone lack-
ing a â iodine, 11c, (Table 4, line 18), would seem incongruent.
The influence of Cγ alkyl substitution on the CR-H exchange
reaction is shown by comparison of the entries on lines 8, 11,
and 15 in Table 4. Whereas the unsubstituted (8a) and the
dimethyl-substituted (8c) â-iodo γ-sultones fully exchange
CR-H under acetate ion catalysis in 5 min, the reaction time
for the monomethyl derivative (8b) is 1.5 h. The higher
activation energy upon monomethyl substitution may be the
result of an inductive effect and/or steric inhibition to solvation,
while the reduction of the activation energy in the gem-dimethyl
derivative 8c is possibly a manifestation of an Ingold-Thorpe
effect, since the formation of the anion is accompanied by
changes in the ring angles. Interestingly, in the reaction of the
‘soft’ thioacetate nucleophile with 8c, the halophilic elimination
to give a fully substituted double bond preempts H-D exchange
even in methanol solution (line 16, Table 4).
12 days
a The sultone concentration was ∼0.06 ( 0.01 M. b Products were
isolated, and mixtures were separated.
SCHEME 4
SCHEME 5
to a carbanion which expels the nucleophile at Câ (Scheme 5).
However, such a pathway seems most unlikely. One of the two
intermediate R-carbanions would be expected to expel the
â-iodide, which is a much better leaving group than the added
nucleophile (other than iodide). In fact, no displacement of the
iodide was observed.
Another possibility might be ionization of the sulfonate
function at Cγ to yield a zwitterion, whose cation moiety is an
allyl carbenium ion. Deprotonation of the latter at CR would
produce an allyl carbene. Capture of a deuteron at CR and
collapse of the zwitterion at Cγ would complete the exchange
process (Scheme 6). This mechanism also appears not to be
operative, since one would certainly expect capture of the
intermediate allyl carbenion species by the methanol solvent
Reverting to the consideration of the simple overall CR
deprotonation-protonation mechanism (Scheme 4), without
going into the details of possible hydrogen-bonded intermediate
complexes, it must be recalled that, in contrast to the findings
for -CHNO2 groupings, proton transfer from -CH-SO2- is
close to ‘normal’ in terms of the Eigen classification.7 In an
isoergonic reaction, it occurs with a rate constant within 2 orders
of magnitude of diffusion control. This has been taken as
(7) Eigen, M. Angew. Chem., Int. Ed. Engl. 1964, 3, 1-19.
6826 J. Org. Chem., Vol. 72, No. 18, 2007

â-Halo-R,â-unsaturated γ-Sultones
TABLE 4. H-D Exchange of the γ-Sultones in CD3OD
t
1/2 (min)
γ-sultone
(0.05 ( 0.01 M)
at ambient
temperature
approximate
basea
k2 (M-1 s-1
)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
7b
7b
7b
7b
7c
7c
8a
8a
8b
8b
8b
8b
8b
8c
8c
8c
NaN3, 2 equiv
,1
7.7
,1
∼6
,1
∼1
,1
∼1
,1
,1
11.6
58
NaN3, 0.05 equiv
CH3C(O)ONa, 2 equiv
CH3C(O)SK, 2 equiv
NaN3, 2 equiv
CH3C(O)SK, 2 equiv
NaN3, 2 equiv
CH3C(O) ONa, 2 equiv
NaN3, 2 equiv
Et3N, 2 equiv
CH3C(O) ONa, 2 equiv
CH3C(O)SK, 2 equiv
NaI, 2 equiv
NaN3, 2 equiv
CH3C(O) ONa, 2 equiv
CH3C(O)SK, 2 equiv
0.6
0.01
0.002
0.001
115
,1
∼1
∼25; only allenesulfonate formed;
no H-D exchange
17
18
8e
11c
NaN3, 2 equiv
NaN3, 2 equiv
,1
∼2300; 55 °C; No reaction at RT
a The pKa values in water at 25 °C for the conjugate acids of the bases are -5.2 for HI, 4.68 for HN3, 3.33 for CH3C(O)SH, 4.74 for CH3C(O)OH, and
11.01 (at 18 °C) for Et3NH+. The pKa value for MeOH is 15.5.
evidence that stabilization of a carbanion R to a SO2 function
is primarily electrostatic, and its formation involves little
structural change due to charge delocalization. Alternatively,
in terms of the Bernasconi formulation,8 the carbanion stabiliza-
tion in the transition state does not lag significantly behind the
proton transfer. Though the intrinsic barrier to proton transfer
from a -CH-SO2- group is, as indicated, very low, yet in an
endergonic process of this type, the specific rate constant is
abstraction does not involve significant conformational adjust-
ment or restriction. (3) Compounds 7 and 8 are sultones, that
is, sulfonate esters, rather than sulfones, and from the Table
presented by Bordwell,10b it appears that CR-H in a linear
sulfonate esters is some 2-3.5 pKa units more acidic on the
DMSO scale than that in the analogous sulfone. In the present
cases of the R,â-unsaturated five-membered ring sultones, the
CR-H and the S-O(-C) bonds of the sultones are fixed anti-
periplanar to each other. The Cσ anion would therefore be
expected to be stabilized by sp2(C)-σ*(S-O) overlap, in addition
to the inductive effect of the third oxygen.14 (4) The CR-H
and Câ-X bonds are coplanar. The vicinal halogen is therefore
expected to enhance CR-H acidity by stabilization of the
resultant CR-carbanion by sp2(C)-σ*(C-X) overlap and by an
inductive effect.15 In fact, the more electronegative Câ-Br is
more effective than Câ-I in enhancing the proton exchange
(compare Table 4, lines 3 and 4 with lines 11 and 12).
reduced by a factor of 10∆pK , where ∆pKa is the difference
a
between the pKa’s of the conjugate acids of the bases between
which the proton transfer is taking place,7 and modified by the
value of the relevant Brønsted coefficient.9 Relating to the
acidity scale in water, the pKa of sulfones lacking additional
activating groups is reported to be about 23,6c while that of
hydrazoic acid and acetic acid (at 25 °C) is 4.59 and 4.76,
respectively,10 Though our observations are for methanol
solution, it is abundantly clear that the rates of proton exchange
found for compounds 7 and 8 are many orders of magnitude
greater than those expected for simple sulfones. In fact,
experimental findings for sulfones in methanol solution con-
firming this conclusion have been reported in the literature.
Thus, 2-octyl-2-d phenyl sulfone in methanol at 100.6 °C in
the presence of methoxide as base (pKa of methanol ) 15.5)
exchanged its isotope with the second-order specific rate
It appears that it is the addition of all four effects to the ability
of an -SO2- function to stabilize an R-carbanion which permits
the observed proton exchange under the mild conditions
described. Thus, as mentioned above, in the absence of a Câ
halogen, 11c, there is no exchange at ambient temperature.
Neither does the γ-sultine 2b show exchange under said
conditions.
constant, k2 ) 7.62 × 10-4 M-1 s-1 11
.
The authors estimated
that at 25 °C k2 ≈ 3 × 10-7 M-1 s-1. Similarly, for 2-methyl-
2,3-dihydrobenzo[b]thiophene 1,1-dioxide in CH3OD solution
in the presence of methoxide at 75.1 °C, k2 of proton exchange
(8) (a) Bernasconi, C. F. Acc. Chem. Res. 1987, 20, 301-308. (b)
Bernasconi, C. F. Acc. Chem. Res. 1992, 25, 9-16.
(9) Unknown, but probably in the region 0.85 ( 0.05; compare Bordwell,
F. G.; Boyle, W. J.; Hautala, J. A.; Yee, K. C. J. Am. Chem. Soc. 1969, 91,
4002-4003, footnote 5.
is 1.79 × 10-4 M-1 s-1 12
.
Clearly, compounds 7 and 8 possess structural features which
contribute to the stabilization of the CR-carbanion, and conse-
quently the acidity of the CR-H, above and beyond the
stabilization afforded by an -SO2- group, to an extent that
very weak bases are capable of abstracting that proton and cause
its rapid exchange. These features are the following. (1) CR is
trigonal and a C(sp2)-H is more acidic than a C(sp3)-H by more
than 5 pKa units. (2) It has been determined that the most stable
conformation of a carbanion R to an SO2 grouping is one in
which the ‘anion orbital’ bisects the OSO angle.13 In the present
case, the CR-H is already located in that position, and its
(10) (a) On the DMSO scale, Bordwell6 reports a pKa value of 28.5 for
dimethyl sulfone and of >31 for tetrahydrothiophene 1,1-dioxide, while
Bordwell,10b quotes a value of 31.1 for dimethyl sulfone. The value for
acetic acid is given as 12.3. (b) Bordwell, F. G. Acc. Chem. Res. 1988, 21,
456-463.
(11) Cram, D. J.; Scott, D. A.; Nielsen, W. D. J. Am. Chem. Soc. 1961,
83, 8696-8707.
(12) Cram, D. J.; Roitman, J. N. J. Am. Chem. Soc. 1971, 93, 2225-
2231.
(13) Cram, D. J. Fundamental of Carbanion Chemistry (Organic
Chemistry, Vol. 4); Academic Press: New York, 1965; Chapter II.
(14) The two effects are of course interrelated.
(15) As for effect 3.
J. Org. Chem, Vol. 72, No. 18, 2007 6827

Braverman et al.
TABLE 5. Relative Proton Affinity (PA), Gas-Phase Basicity (GB), and Relative Protonation Free Energy in Methanol Solution (kcal/mol)
a PA ) -∆Hprot b GB ) -∆Gprot c Gas-phase - mPW1PW91/6-311++G(3df,2p)//mPW1PW91/6-31+G(d) and Cosmo continuum model (Methanol)
. .
with PW1/DND at PW1/DND gas-phase geometry. d Single conformation only.
To investigate the inherent (free of solvation effects) relative
contributions of the above-mentioned factors to the stabilization
of the R-carbanion, we turned to theoretical calculations. As
reference point, we took the R-carbanion of the â-bromo
γ-sultone 7a and calculated the relative proton affinity (PA )
-∆Hprotonation) and gas-phase basicity (GB ) -∆Gprotonation) of
the R-carbanions of the molecules listed in Table 5. All
geometries were optimized employing the mPW91PW91
density functional with the 6-31+G(d) basis set. When these
optimized geometries were used, single-point energy calculations
were performed at the mPW91PW91/6-311++G(3df,2p)//
mPW91PW91/6-31+G(d) level. All gas-phase calculations
employed the Gaussian 03 program. The last column in Table
5 presents the calculated relative -∆G of protonation in solution
of dielectric constant 32.6, corresponding to methanol, using
the COSMO continuum model (Accelrys Inc). Additional details
of calculations, as well as coordinates for the neutral molecules
and their anions are to be found in the Supporting Information.
Calculations for dimethyl sulfone (16) are included in Table 5
for the purpose of “order of magnitude” comparison, as its pKa
in DMSO has been reported as 31.1.10b
between the O-S-O bonds.16 Effect (3) finds expression in
the differences [∆GB(13) - ∆GB(7a)] ) 8.2 kcal/mol, [∆GB-
(14) - ∆GB(11a)] ) 7.9 kcal/mol, and [∆GB(15) - ∆GB-
(12)] ) 7.8 kcal/mol. Effect (4), the contribution of a â-halogen,
exemplified by that of the â-bromine, is given by [∆GB(11a)
- ∆GB(7a)] ) 13.4 kcal/mol and by [∆GB(14) - ∆GB(13)]
) 13.1 kcal/mol. The near equality of the free energy values
attributable to each one of the effects, even though arrived at
from the comparison of different molecules, is impressive. Even
more so is the near additivity of these values. Effects (1) + (2)
+ (3) are represented by [∆GB(15) - ∆GB(11a)] ) 14.9 kcal/
mol, while addition (7.0/7.1 + 8.2/7.9/7.8) yields a value of
14.8-15.3 kcal/mol. For effect (1) + (2) + (4), represented by
[∆GB(12) - ∆GB(7a)] ) 20.5 kcal/mol or [∆GB(15) - ∆GB-
(13)] ) 20.1 kcal/mol, addition (7.0/7.1 + 13.1/13.4) gives
20.1-20.5 kcal/mol. The combination of effects (3) + (4) is
available from [∆GB(14) - ∆GB(7a)] ) 21.3 kcal/mol, while
addition (8.2/7.9/7.8 + 13.1/13.4) leads to 20.9-21.6 kcal/mol.
The sum of all four effects is given by [∆GB(15) - ∆GB(7a)]
) 28.3 kcal/mol, and addition (7.0/7.1 + 8.2/7.9/7.8 + 13.1/
13.4) gives the range of 27.9-28.7 kcal/mol. It seems intuitively
Referring to the gas-phase data for the cyclic molecules in
Table 5, the combined effect of factors (1) and (2) above is
expressed by the difference [∆GB(12) - ∆GB(11a)] ) 7.1 kcal/
mol, and by the difference [∆GB(15) - ∆GB(14)] ) 7.0 kcal/
mol. In the anions of both 12 and 15, the CR has a distorted
tetrahedral geometry, and the remaining CR-H is out of ‘the
plane’ of the ring, positioning the ‘anion orbital’ staggered
(16) For 12, the angles are (S-CR-H) ) 106.25°, (Câ-CR-H) )
112.79°. The torsional angles are (O-S-CR-H) ) 92.37°, (Cγ-Câ-
CR-H) ) -74.14°, (O′-S-CR-H) ) -20.98° (O′-sulfonyl oxygen),
(O′′-S-CR-H) ) -160.75° (O′′-sulfonyl oxygen). For 15, the angles are
(S-CR-H) ) 107.14°, (Câ-CR-H) ) 113.26°. The torsional angles are
(Cδ-S-CR-H) ) 94.30°, (Cγ-Câ-CR-H) ) -73.22°, (O′-S-CR-
H) ) -21.80° (O′-sulfonyl oxygen), (O′′-S-CR-H) ) -157.26° (O′′-
sulfonyl oxygen).
6828 J. Org. Chem., Vol. 72, No. 18, 2007

â-Halo-R,â-unsaturated γ-Sultones
TABLE 6. Changes in Bond Lengths upon r-Carbanion Formation (Å)a
bond
7a
11a
12
bond
S-CR
CR-Câ
Câ-Cγ
Cγ-Cδ
Cδ-S(O)2
S-O
13
14
15
S-CR
-0.030
+0.002
+0.012
-0.012
+0.073
+0.017
+0.017
+0.070
-0.022
+0.021
+0.021
-0.015
+0.080
+0.019
+0.019
-0.129
-0.012
+0.022
-0.021
+0.120
+0.023
+0.019
-0.031
0.000
-0.019
+0.020
+0.026
-0.007
+0.035
+0.019
+0.021
-0.117
-0.011
+0.027
+0.002
+0.052
+0.022
+0.022
CR-Câ
Câ-Cγ
Cγ-O
+0.014
-0.003
+0.034
+0.016
+0.018
+0.080
O-S(O)2
S-O
sulfonyl
Câ-Br
sulfonyl
Câ-Br
a For 16, ∆ S-CR ) -0.126 Å; ∆ S-CR′ ) +0.048 Å; ∆ S-O ) +0.026 Å.
reasonable that such additivity is evidence for a high degree of
charge localization and would not pertain if the negative charge
were highly delocalized into the -SO2- grouping. In any case,
it is clear that of the four effects postulated above, it is the anion
stabilizing effect of the vicinal halogen which is the dominant
one.
which the ring structure is more inflexible. In keeping with the
analysis of the energy data, the other major changes are
lengthening of the Câ-Br bonds and the O-S(O)2 and Cδ-
S(O)2 bonds.
Experimental Section
The assumptions inherent in the solvation energy calculations
make even relative values much less reliable than those of gas-
phase calculations, especially in case of hydrogen-bonding
solvents such as methanol. However, they remain informative.
In the present case, the free energies of solvation of the neutral
molecules in Table 5 all lie within the range of -11.3 (for 7a)
to -12.7 kcal/mol (for 11a), while for the anions, the values
range from -57.8 (for 7a anion) to -66.6 kcal/mol (for 14
anion), as detailed in the Supporting Information (Table S2).
The derived free energies of protonation in methanol solution
listed in column 5 of Table 5 may be analyzed with regard to
the contributions of the above-mentioned effects to anion
stability, in the manner done for the gas-phase data. Not
surprisingly, the values derived for a particular effect from two
pairs of compounds are less precise varying by up to 1.7 kcal/
mol. Thus, for factors (1) + (2), [∆∆Gsol(12) - ∆∆Gsol(11a)]
) 5.9 kcal/mol, while [∆∆Gsol(15) - ∆∆Gsol(14)] ) 7.5 kcal/
mol. For effect (3), [∆∆Gsol(13) - ∆∆Gsol(7a)] ) 5.1 kcal/
mol, [∆∆Gsol(14) - ∆∆Gsol(11a)] ) 3.4 kcal/mol, and [∆∆Gsol-
(15) - ∆∆Gsol(12)] ) 5.0 kcal/mol. For effect (4), [∆∆Gsol(11a)
- ∆∆Gsol(7a)] ) 10.4 kcal/mol and [∆∆Gsol(14) - ∆∆Gsol-
(13)] ) 8.7 kcal/mol. However, if for each effect an average of
its values is taken, near additivity remains. Thus, for effects
(1) + (2) + (3), [∆∆Gsol(15) - ∆∆Gsol(11a)] ) 10.9 kcal/
mol, while addition of averages gives 11.2 kcal/mol. For effects
(1) + (2) + (4), [∆∆Gsol(12) - ∆∆Gsol(7a)] ) 16.3 kcal/mol
and [∆∆Gsol(15) - ∆∆Gsol (13)] ) 16.2 kcal/mol, while
addition of averages yields 16.25 kcal/mol. For effects (3) +
(4), [∆∆Gsol(14) - ∆∆Gsol(7a)] ) 13.8 kcal/mol, while addition
of averages yields 14.05 kcal/mol. The sum of all four effects,
given by [∆GB(15) - ∆GB(7a)] ) 21.3 kcal/mol and addition
of averages lead to 20.75 kcal/mol. Predictably, solvation has
but little influence on effects (1) + (2), and most influence on
effect (3). Though the energy value of effect (4) is reduced, it
remains dominant.
General procedure for the preparation of γ-sultines, including
characterization data for compounds 2a-c were recently reported
by us.1a
4-Iodo-1-oxa-2-thiaspiro[4.5]dec-3-ene 2-oxide (2d). (Yield
70%) Was purified by column chromatography using silica gel and
hexane/ethyl acetate in the ratio 5:1, respectively, as eluent, and
was obtained as a yellow liquid.
1H NMR (300 MHz, CDCl3): δ 6.89 (s, 1H), 2.14-1.95 (m,
2H), 1.90-1.82 (m, 1H), 1.81-1.72 (m, 5H), 1.52-1.48 (m, 1H),
1.31-1.17 (m, 1H). 13C NMR (150 MHz, CDCl3): δ 139.9 (d
CH-), 116.2 (dC-), 103.2 (-C-), 36.8 (-CH2-), 35.5 (-CH2-
), 24.3 (-CH2-), 21.7 (-CH2-), 21.6 (-CH2-). IR (neat): 1124,
1575, 2936 cm-1. MS (CI/CH4): m/z 299 (MH+, 41%), 250 (6%),
171 (8%), 79 (100%). HRMS (elemental composition): calcd
(C8H12O2SI) 298.9603; found 298.9600.
4-Iodo-5-phenyl-5H-1,2-oxathiole 2-oxide (2e). (Yield 54%)
The two diastereoisomers were separated by column chromatog-
raphy using silica gel and hexane/ethyl acetate in the ratio 200:5,
respectively, as eluent. The crystals were white needles.
For the first isomer (less polar), mp 105-106 °C. 1H NMR (300
MHz, CDCl3): δ 7.49-7.40 (m, 5H), 7.07 (d, J ) 2.1 Hz, 1H),
6.03 (d, J ) 2.1 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 141.6
(dCH-), 133.7 (dC- ipso), 129.8, 130.0, 128.8 (dCH-, Ph),
108.6 (dC-), 102.0 (-CH-). For the second isomer (more polar),
1
mp 117-118 °C. H NMR (300 MHz, CDCl3): δ 7.46-7.42 (m,
3H), 7.27-7.24 (m, 2H), 7.13 (d, J ) 2.1 Hz, 1H), 6.45 (d, J )
2.1 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 142.9 (dCH-), 133.4
(dC-, ipso), 130.2, 129.0, 128.2 (dCH-, Ph), 109.7 (dC-), 99.6
(-CH-). For the mixture of isomers, IR (neat): 1123, 1127 1574,
1578 cm-1. MS (CI/CH4): m/z 307 (MH+, 0.8%), 306 (M+, 0.7%),
258 ((M-SO)+, 2%), 241 (3%). HRMS (elemental composition):
calcd (C9H8O2SI) 306.9290; found 306.9290.
Oxidation of γ-Sultines to γ-Sultones: General Procedure.
To 20 mL of a cooled (0 °C) CH2Cl2 solution of the appropriate
γ-sultine (5 mmol), a solution of m-CPBA (12.5 mmol) in 20 mL
of CH2Cl2 was added dropwise with stirring. After a further 30
min at 0 °C, the reaction mixture was stirred for 24 h at ambient
temperature. The CH2Cl2 solution was washed with aqueous
solutions of KI/Na2S2O3 (3 times), NaHCO3 (3 times), and then
with water. After drying (MgSO4) and removal of the solvent, the
products were recrystallized from ether or were separated by column
chromatography using silica gel with hexane/ethyl acetate as eluent.
γ-Sultones 7b,1d 7c,1c,d and 11c1c were reported previously.
4-Iodo-5H-1,2-oxathiole 2,2-dioxide (8a). (Yield 76%) Was
obtained as a white solid upon silica gel chromatography, using
hexane/ethyl acetate in the ratio 3:1, respectively, as eluent.
Mp 96-98 °C. 1H NMR (300 MHz, CDCl3): δ 7.12 (t, J ) 2.1
Hz, 1H), 5.03 (d, J ) 2.1 Hz, 2H). 13C NMR (75 MHz, CDCl3):
As the molecules under consideration are cyclic, a change in
one of the geometric parameters of the ring, bond length or
angle, necessarily induces a change in some others, and unless
the change is large, one cannot be sure if it is of primary
significance or if it is a secondary adjustment. Perusing the
geometric changes accompanying the conversion of the neutral
sultones and sulfones to their R-anions in Table 6, one finds
the expected S-CR bond lengthening to be much greater in the
saturated structures, 12 and 15, where CR is sp3 hybridized, than
in the unsaturated structures where it is sp2 hybridized, and in
J. Org. Chem, Vol. 72, No. 18, 2007 6829

Braverman et al.
δ 130.2 (dCH-), 102.2 (dC-), 78.6 (-CH2-). IR (neat): 1165,
1220, 1354, 1597, 3105 cm-1. MS (CI/CH4): m/z 246 (M+, 100%),
182 ((M-SO2)+, 6%), 152 ((I-CtC-H)+, 33%), 127 (I+, 27%),
119 ((M-I)+, 55%). HRMS (elemental composition): calcd
(C3H3O3SI) 245.8848; found 245.8850.
4-Iodo-5-methyl-5H-1,2-oxathiole 2,2-dioxide (8b). (Yield
82%) Was obtained as a white solid after recrystallization from
cold ether/pentane.
Mp 86-87 °C. 1H NMR (300 MHz, CDCl3): δ 7.04 (d, J ) 2.0
Hz, 1H), 5.27 (qd, J ) 7.0, 2.0 Hz, 1H), 1.68 (d, J ) 7.0 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 131.1 (dCH-), 110.1 (dC-),
86.8 (-CH-), 20.2 (-CH3). IR (neat): 1165, 1218, 1342, 1591,
3094 cm-1. MS (CI/CH4): m/z 261 (MH+, 26%), 260 (M+, 95%),
245 ((M- CH3)+, 33%), 181 ((C4H6I+), 11%), 152 ((I-CtC-
H)+, 38%), 133 ((M-I)+, 100%), 127 (I+, 15%). HRMS (elemental
composition): calcd (C4H5O3SI) 259.9004; found 259.9004.
4-Iodo-5,5-dimethyl-5H-1,2-oxathiole 2,2-dioxide (8c). (Yield
89%) Was obtained as a white solid after recrystallization from
cold ether/pentane.
Mp 95-96.5 °C. 1H NMR (300 MHz, CDCl3): δ 6.93 (s, 1H),
1.67 (s, 6H). 13C NMR (75 MHz, CDCl3): δ 131.2 (dCH-), 116.3
(dC-), 94.7 (-C-), 26.9 (2×(-CH3)). IR (neat): 1151, 1216,
1346, 1591 cm-1. MS (CI/CH4): m/z 274 (MH+, 42%), 259 ((M-
CH3)+, 100%), 86 (36%), 84 (58%). HRMS (elemental composi-
tion): calcd (C5H7O3SI) 273.9161; found 273.9159.
4-Iodo-1-oxa-2-thiaspiro[4.5]dec-3-ene 2,2-dioxide (8d). (Yield
78%) Was obtained as a white solid upon silica gel chromatography,
using hexane/ethyl acetate in the ratio 5:1, respectively, as eluent,
of the cold ether soluble portion of the crude oxidation product.
Mp 114-115 °C. 1H NMR (300 MHz, CDCl3): δ 6.95 (s, 1H),
1.99-1.67 (m, 9H), 1.31-1.18 (m, 1H). 13C NMR (75 MHz,
CDCl3): δ 130.6 (dCH-), 117.0 (dC-), 96.5 (-C-), 34.6
(-CH2-), 23.9 (-CH2-), 21.3 (-CH2-). IR (neat): 1171, 1223,
1339, 1514 cm-1. MS (CI/CH4): m/z 314 (M+, 2%), 187 (50%),
139 (100%). HRMS (elemental composition): calcd (C8H11O3SI)
313.9474; found 313.9459.
Sodium 2-Cyclohexylideneethylenesulfonate (9d, R ) Na+
Salt). (Yield 100%) Was obtained as a white solid.
1H NMR (600 MHz, CD3OD): δ 5.94 (quint, J ) 1.8 Hz, 1H),
2.26-2.21 (m, 4H), 1.75-1.67 (m, 2H), 1.62-1.54 (m, 4H). 13C
NMR (150 MHz, CD3OD): δ 198.1 (dCd), 110.3 (dC-),
98.3 (dCH-), 31.7 (2×(-CH2-)), 28.0 (2×(-CH2-)), 26.9
(-CH2-). MS (ES-): m/z 187 (M-, 100%). HRMS FB- (elemental
composition): calcd (C8H11O3S) 187.0429; found 187.0428.
Sodium 3-Phenylallene-1-sulfonate (9e, R ) Na+ Salt). (Yield
100%) Was obtained as a white solid.
1H NMR (300 MHz, CD3OD): δ 7.39-7.20 (m, 5H), ABq: 6.63
and 6.55 (d, J ) 6.3 Hz, 1H each). 13C NMR (75 MHz, CD3OD):
δ 205.3 (dCd), 134.0 (dC-, ipso), 129.7 (dCH-), 128.8 (d
CH-), 128.5 (dCH-) (Ar), 104.0 (dCH-), 100.6 (dCH-). MS
(ES-): m/z 195 (M-, 100%). HRMS FB- (elemental composi-
tion): calcd (C9H7O3S) 195.0116; found 195.0126.
Reaction of â-Halo γ-Sultones with NaN3 (2 equiv) in DMSO.
To a solution of the appropriate γ-sultone (∼0.06 ( 0.01 M) in
d6-DMSO in an NMR tube at room temperature, was added sodium
azide (2 equiv). The reaction mixture was shaken and kept at room
temperature for the appropriate time, determined by 1H NMR (Table
3). Then, methylene chloride was added, and the organic mixture
was washed with water 10 times. After drying over anhydrous
MgSO4 and removal of the solvent under reduced pressure, the
products were isolated and mixtures separated by column chroma-
tography using silica gel with chloroform as eluent.
2,2-Dioxido-5H-1,2-oxathiol-4-yl azide (10a). (Yield 100%)
Was obtained as a colorless liquid.
1H NMR (300 MHz, CDCl3): δ 6.43 (t, J ) 1.8 Hz, 1H), 4.83
(d, J ) 1.8 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 150.3
(dC-), 106.4 (dCH-), 69.2 (-CH2-). IR (neat): 1171, 1288,
1347, 1617, 2129, 2164, 3104 cm-1. MS (CI/CH4): m/z 162 (MH+,
70%), 119 (26%), 104 (100%), 103 (92%), 69 (64%). HRMS
(elemental composition): calcd (C3H4N3O3S) 161.9973; found
161.9969.
4-Azido-5-methyl-5H-1,2-oxathiole 2,2-dioxide (10b). (Yield
100%) Was obtained as a colorless liquid.
4-Iodo-5-phenyl-5H-1,2-oxathiole 2,2-dioxide (8e). (Yield 82%)
Was obtained as a white crystals after recrystallization from cold
ether and washing with pentane.
1H NMR (300 MHz, CDCl3): δ 6.39 (d, J ) 1.5 Hz, 1H), 5.06
(qd, J ) 6.6, 1.5 Hz, 1H), 1.58 (d, J ) 6.6 Hz, 3H). 13C NMR (75
MHz, CDCl3): δ 154.2 (dC-), 106.0 (dCH-), 78.8 (-CH-),
18.5 (-CH3). IR (neat): 1170, 1271, 1344, 1614, 2125, 2158, 3092
cm-1. MS (CI/CH4): m/z 176 (MH+, 99%), 104 (55%), 84 (100%).
HRMS (elemental composition): calcd (C4H6N3O3S) 176.0129;
found 176.0130.
1
Mp 149.5-150.5 °C. H NMR (300 MHz, CDCl3): δ 7.49-
7.46 (m, 3H), 7.40-7.37 (m, 2H), 6.18 (d, J ) 2.1 Hz, 1H), 6.02
(d, J ) 2.1 Hz, 1H). 13C NMR (75 MHz, CDCl3): δ 132.4 (dC-
ipso), 130.7 (dCH-), 130.7 (dCH-), 129.2 (dCH-), 128.1 (d
CH-), 109.6 (dC-), 91.4 (-CH-). IR (neat): 1160, 1213, 1340,
1646 cm-1. MS (CI/CH4): m/z 322 (M+, 11%), 241 (39%), 195
(21%), 131 (60%), 115 (100%). HRMS (elemental composition):
calcd (C9H7O3SI) 321.9161; found 321.9178.
4-Azido-5,5-dimethyl-5H-1,2-oxathiole 2,2-dioxide (10c). (Yield
100%) Was obtained as a white solid.
1
Mp 93-94 °C. H NMR (300 MHz, CDCl3): δ 6.29 (s, 1H),
1.61 (s, 6H). 13C NMR (75 MHz, CDCl3): δ 157.4 (dC-), 105.4
(dCH-), 88.3 (-C-), 25.5 (2×(-CH3)). IR (neat): 1154, 1248,
1326, 1614, 2150, 3085 cm-1. MS (CI/CH4): m/z 190 (MH+, 3%),
86 (68%), 84 (100%). HRMS (elemental composition): calcd
(C5H8N3O3S) 190.0278; found 190.0286.
Conversion of â-Iodo γ-Sultones (8) to Allenesulfonates (9).
To a solution of the appropriate γ-sultone (∼0.05 ( 0.01 M) in
d6-DMSO or d6-acetone in an NMR tube was added the appropriate
nucleophile (Table 2), and the reaction mixture was shaken. After
the appropriate time at room temperature (except in one case, 8b
with NaI at 56 °C), determined by 1H NMR, the pure sodium
allenesulfonate salts were precipitated from the acetone solutions,
washed with d6-acetone, and dried in the air.
H-D Exchange of the γ-Sultones in CD3OD. To a solution of
the appropriate γ-sultone (∼0.05 ( 0.01 M) in CD3OD in an NMR
tube at room temperature (except in one case, 11c at 55 °C) was
added the appropriate base (Table 4), and the reaction mixture was
Sodium Buta-1,2-diene-1-sulfonate (9b, R ) Na+ Salt). (Yield
100%).
1
shaken. After the appropriate time, determined by H NMR, the
solvent was removed under reduced pressure, and the products were
isolated.
1H NMR (300 MHz, d6-DMSO): δ 5.86 (dq, J ) 6.0, 3.0 Hz,
1H), 5.33 (qd, J ) 7.2, 6.0 Hz, 1H), 1.63 (dd, J ) 7.2, 3.0 Hz,
3H). 13C NMR (150 MHz, d6-DMSO): δ 201.3 (dCd), 101.4
(dCH-), 89.1 (dCH-), 21.1 (-CH3).
Computational Methods. All species were optimized employing
the mPW91PW91 density functional17 with the 6-31+G(d) basis
set.18 Frequency calculations were performed to analyze the
stationary points on the potential energy surface, and these
confirmed the location of minimum energy structures. Subsequently,
single-point calculations were performed at the mPW91PW91/6-
Sodium 3-Methylbuta-1,2-diene-1-sulfonate (9c, R ) Na+
Salt). (Yield 100%) Was obtained as a white solid.
1H NMR (600 MHz, CD3OD): δ 5.94 (septet, J ) 2.7 Hz, 1H),
1.79 (d, J ) 2.7 Hz, 6H). 13C NMR (150 MHz, CD3OD): δ 201.2
(dCd), 103.4 (dC-), 98.5 (dCH-), 20.0 (2×(-CH3)). MS
(ES-): m/z 147 (M-, 100%). HRMS FB- (elemental composi-
tion): calcd (C5H7O3S) 147.0116; found 147.0121.
(17) Adamo, C.; Barone, V. J. Chem. Phys. 1998, 108, 664-675.
(18) Hehre, W. J.; Radom, L.; Schleyer, P. V. R.; Pople, J. A. Ab Initio
Molecular Orbital Theory; John Wiley & Sons: New York, 1986.
6830 J. Org. Chem., Vol. 72, No. 18, 2007

â-Halo-R,â-unsaturated γ-Sultones
311++G(3df,2p)//mPW91PW91/6-31+G(d) level. Zero-point en-
ergy and thermal corrections were obtained by employing standard
statistical mechanics expressions. These corrections were added to
the electronic energy to obtain the proton affinity (PA) and gas-
phase basicity (GB) at 298.15 K. All gas-phase calculations
employed the Gaussian 03 program.19
the PW91PW91 density functional23 and a double-ú numerical basis
set with d-functions (DND) as implemented in the DMol3 program
(Accelrys Inc).24 A dielectric constant corresponding to methanol
was employed (32.6). Both methods gave similar results.
Acknowledgment. This research was supported by THE
ISRAEL SCIENCE FOUNDATION (Grant No. 919-05).
The effect of solvent was accounted for via single-point
calculations within the continuum approximation. Initially, the
Polarizable Continuum Model (PCM)20 was employed with the
PBEPBE/6-31+G(d)21 functional and UAKS (United Atom Kohn-
Sham) atomic group radii as implemented in Gaussian 03. Ad-
ditionally, the COSMO method22 was employed in conjunction with
Supporting Information Available: 1H NMR and 13C NMR
spectra for all new compounds (2d,e, 8a-e, 9b-e, 10a-c). Spectral
data and 1H NMR spectra for deuterated γ-sultones (R-D-7b, R-D-
7c, R-D-8a, R-D-8b, R-D-8c, R-D-8e, R-D-11c). 1H NMR spectra
for known compounds 7b, 7c, and 11c. Calculation data, including
Cartesian coordinates, total energy, and number of imaginary
frequencies for molecules of Table 5 and their anions (PDF). This
material is available free of charge via the Internet at http://pubs.
acs.org.
(19) Gaussian 03, Revision C.01; Gaussian, Inc.: Pittsburgh, PA, 2003.
Complete reference is given in the Supporting Information.
(20) Miertus, S.; Scrocco, E.; Tomasi, J. Chem. Phys. 1981, 55, 117-
129.
JO071085Q
(21) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. ReV. Lett. 1996, 77,
(23) Perdew, J. P.; Burke, K.; Wang, Y. Phys. ReV. B 1996, 54, 16533-
16539.
(24) (a) Delley, B. J. Chem. Phys. 1990, 92, 508-517. (b) Delley, B. J.
Chem. Phys. 2000, 113, 7756-7764.
3865-3868.
(22) Andzelm, J.; Kolmel, C.; Klamt, A. J. Chem. Phys. 1995, 103,
9312-9320.
J. Org. Chem, Vol. 72, No. 18, 2007 6831