Preparation, properties, and chemical reactivity of α-nitrosulfoximines, chiral analogues of α-nitrosulfones

Article abstract of DOI:10.1021/jo010924k

Racemic N-methyl-S-(nitromethyl)-S-phenylsulfoximine (2) was prepared in 87% yield via alkaline nitration of N,S-dimethyl-S-phenylsulfoximine. Optically active N-methyl-S-(nitromethyl)-S-phenylsulfoximine (both enantiomers) was prepared in similar fashion. Reaction of racemic 2 with p-chlorophenyl isocyanate and a catalytic quantity of triethylamine in the presence of furan afforded dihydrofuroisoxazole 5, the product of nitrile oxide cycloaddition, in 42% yield (65:35 diastereomer ratio). Reaction of the dihydrofuroisoxazole 5 with phenyllithium and methyllithium afforded replacement of the sulfoximine group by phenyl and methyl, respectively. Reaction of racemic 2 with aromatic isocyanates and potassium carbonate afforded C-acylation products in 70-78% yield which existed as the ylide tautomers 9a,b. Methylation of racemic 2 afforded the C-alkylate N-methyl-S-(1-nitroethyl)-S-phenylsulfoximine (13), existing as the neutral tautomer.

Full text of DOI:10.1021/jo010924k

J . Org. Chem. 2002, 67, 2859-2863
2859
P r ep a r a tion , P r op er ties, a n d Ch em ica l Rea ctivity of
r-Nitr osu lfoxim in es, Ch ir a l An a logu es of r-Nitr osu lfon es
Peter A. Wade,* Hung Le, and Nayan V. Amin
Department of Chemistry, Drexel University, Philadelphia, Pennsylvania 19104
Received September 17, 2001
Racemic N-methyl-S-(nitromethyl)-S-phenylsulfoximine (2) was prepared in 87% yield via alkaline
nitration of N,S-dimethyl-S-phenylsulfoximine. Optically active N-methyl-S-(nitromethyl)-S-phen-
ylsulfoximine (both enantiomers) was prepared in similar fashion. Reaction of racemic 2 with
p-chlorophenyl isocyanate and a catalytic quantity of triethylamine in the presence of furan afforded
dihydrofuroisoxazole 5, the product of nitrile oxide cycloaddition, in 42% yield (65:35 diastereomer
ratio). Reaction of the dihydrofuroisoxazole 5 with phenyllithium and methyllithium afforded
replacement of the sulfoximine group by phenyl and methyl, respectively. Reaction of racemic 2
with aromatic isocyanates and potassium carbonate afforded C-acylation products in 70-78% yield
which existed as the ylide tautomers 9a ,b. Methylation of racemic 2 afforded the C-alkylate
N-methyl-S-(1-nitroethyl)-S-phenylsulfoximine (13), existing as the neutral tautomer.
R-Nitrosulfoximines, chiral analogues of R-nitrosul-
fones, have never been reported in the literature. Here
we report the synthesis, properties, and chemical reactiv-
ity of several members of this new class of compounds.
Racemic N,S-dimethyl-S-phenylsulfoximine (1), avail-
able via the procedure of J ohnson et al.,1 underwent
alkaline nitration to afford N-methyl-S-(nitromethyl)-S-
phenylsulfoximine (2), the parent R-nitrosulfoximine. Our
initial studies employed butyllithium and LDA as bases
with commercially available isobutyl nitrate as the
nitrating agent. R-Nitrosulfoximine 2 was obtained under
these conditions but only in 10-20% yield.
The proton NMR spectra of R-nitrosulfoximine 2 were
strongly reminiscent of alcohol spectra (Figure 1). Like
the O-H proton of an alcohol, the diastereotopic meth-
ylene protons of R-nitrosulfoximine 2 showed a significant
concentration dependence. In dilute (0.06 M) deuterio-
chloroform solution, 2 exhibited two sharp doublets at δ
5.70 and 5.60 (J ) 11.1 Hz) attributed to the methylene
protons. In more concentrated solution (3.5 M), both
signals occurred at lower field (δ 5.83 and 5.76, respec-
tively) with little or no apparent broadening or change
in the coupling constant. However, impure samples of 2
did show appreciable line broadening of the methylene
proton signals. Furthermore, the methylene protons of
2 underwent relatively rapid exchange (<2 min) at pH 7
when a deuteriochloroform solution of 2 was brought into
contact with deuterium oxide. In contrast, the more acidic
(phenylsulfonyl)nitromethane (pKa 5.74), which lacks a
basic site, did not undergo appreciable exchange under
these conditions.
Truce and Feuer et al.2 have reported the similar
alkaline nitration of sulfones. They attributed higher
yields to avoidance of overly strong bases and suggested
a possible preference for the potassium rather than
lithium counterion. We were gratified to obtain R-nitro-
sulfoximine 2 in 87% yield using commercially available
potassium hexamethyldisilamide (KHMDS) rather than
LDA or butyllithium as the base. In similar fashion,
alkaline nitration of (R)-(-)-1 afforded (S)-(+)-N-methyl-
S-(nitromethyl)-S-phenylsulfoximine (2) and alkaline
nitration of (S)-(+)-1 afforded (R)-(-)-2. Optically pure
samples of the starting sulfoximine 1 were prepared by
the excellent procedure of Brandt and Gais.3
Sulfoximines as a class are known to be basic, the
imine N-atom undergoing protonation and also meth-
ylation.1 The R-nitrosulfoximine 2 is also relatively
acidic: its first pKa, measured in 50:50 methanol/water,
was 6.3. Thus, R-nitrosulfoximine 2 is an amphoteric
compound.
The diastereotopic methylene protons of R-nitrosulfox-
imine 2 also showed clear indication of rapid exchange
under both acidic and basic conditions. In the presence
of a trace of acetic acid, line broadening and partial
coalescence of the methylene proton signals were ob-
served. Formation of an iminium ion and subsequent
formation of the transient ylide 3 from the imminium ion
would explain these observations (Scheme 1). The effect
of a small amount of triethylamine on 2 was even more
pronounced than the effect of acid: line broadening was
more severe for the same quantity of catalyst. Here
equilibration must have occurred via formation and
reprotonation of the nitronate.
Our original interest in preparing 2 was its potential
for conversion to a chiral nitrile oxide analogous to
achiral (phenylsulfonyl)carbonitrile oxide5 (Scheme 2). It
has previously been shown that (phenylsulfonyl)carbo-
nitrile oxide is an effective 1,3-dipole undergoing cycload-
dition to a wide variety of alkenes, even alkenes that are
(1) J ohnson, C. R.; Haake, M.; Schroeck, C. W. J . Am. Chem. Soc.
1970, 92, 6594. J ohnson, C. R.; Schroeck, C. W.; Shanklin, J . R. J .
Am. Chem. Soc. 1973, 95, 7424.
(2) Truce, W. E.; Klingler, T. C.; Paar, J . E.; Feuer, H.; Wu, D. K. J .
Org. Chem. 1969, 34, 3104.
(3) Brandt, J .; Gais, H.-J . Tetrahedron: Asymmetry 1997, 8, 909.
(4) Bordwell, F. G.; Bartmess, J . E. J . Org. Chem. 1978, 43, 3101.
(5) Wade, P. A.; Hinney, H. R. J . Am. Chem. Soc. 1979, 101, 1319.
Wade, P. A.; Pillay, M. K. J . Org. Chem. 1981, 46, 5425.
10.1021/jo010924k CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/27/2002

2860 J . Org. Chem., Vol. 67, No. 9, 2002
Wade et al.
F igu r e 1. Stacked 1H NMR spectra of R-nitrosulfoximine 2.
Sch em e 1
Sch em e 2
sluggish in reaction with other nitrile oxides.5 Further-
more, the sulfone group present in the resulting dihy-
droisoxazoles can be readily replaced by nucleophiles,
thus affording a general synthesis of dihydroisoxazoles
from a single nitrile oxide precursor.6
It was anticipated that a general asymmetric synthesis
of dihydroisoxazoles based on optically active 2 might be
possible. This matter has been tested with racemic 2
pursuant to the development of an actual asymmetric
synthesis. Furan, a well-known sluggish dipolarophile,
was chosen as the olefinic component for examination.
Warming a solution of racemic 2, p-chlorophenyl isocy-
anate, furan, and a catalytic quantity of triethylamine
in chloroform did indeed afford a 42% yield of the nitrile
oxide cycloaddition product dihydrofuroisoxazole 5. Ster-
eochemical induction was moderate: a mixture of dia-
stereomers (65:35 isomer ratio, major isomer not deter-
mined) was obtained. These diastereomers could be
partially separated into enriched fractions by thin-layer
(6) Wade, P. A.; Yen, H.-K.; Hardinger, S. A.; Pillay, M. K.; Vail, P.
D.; Morrow, S. D. J . Org. Chem. 1983, 48, 1796.

Preparation of R-Nitrosulfoximines
J . Org. Chem., Vol. 67, No. 9, 2002 2861
metric NO2 stretching bands (νas 1425 cm-1 and νs 1327
cm-1) characteristic of a nitronate rather than a nitro
group.
Sch em e 3
It seems unusual for the zwitterionic ylide tautomers
9a ,b to be favored over the neutral tautomers 8a ,b.
Formation of the ylide tautomers 9a ,b might well be
driven by intramolecular H-bonding. Perhaps H-bonding
from the amide proton to one nitronate O-atom and from
the iminium proton to the other nitronate O-atom occurs,
resulting in stabilization of the ylide tautomer. Such
double stabilization of nitronates has a precedent.9
The nitro group is especially capable of stabilizing
adjacent carbanions. Thus, there are a number of known
stable nontautomerizable ylides (e.g., 11a -c) involving
sulfonium cations adjacent to nitronate centers.10 It was
desired to prepare examples of this class for comparison
to ylides 9a ,b. Consequently, the previously unreported
ylides 12a ,b were synthesized from (phenylsulfonyl)-
nitromethane using oxalyl chloride under Swern11 condi-
tions.
chromatography, but complete separation has not yet
been obtained.
There can be little doubt that nitrile oxide 4, the first
sulfoximinyl nitrile oxide, was an intermediate in the
formation of dihydrofuroisoxazole 5. Apparently, O-
acylation of 2 occurred followed by elimination. However,
if more than a catalytic amount of triethylamine was
employed, there was a competing side reaction. For
example, in the presence of 0.25 molar equiv of triethyl-
amine, ylide 9a was obtained in 20% yield (Scheme 3).
Apparently 9a was derived from C-acylation of the anion
of 2 and ensuing tautomerization.
To complete the initial test of the generality of dihy-
droisoxazole synthesis using nitrosulfoximine 2, the
replacement of the sulfoximine group was investigated.
Reaction of 5 with phenyllithium in THF at -78 °C
afforded the dihydrofuroisoxazole 6a in 48% yield as well
as the sulfinamide 77 as a byproduct. Similarly, reaction
of 5 with methyllithium afforded 6b in 54% yield.
Thus, the initial test demonstrates that 2 is capable
of affording the sulfoximinyl nitrile oxide and cycload-
ducts derived from it. If optically active 2 were used, the
cycloadducts that would be formed should be nonracemic
diastereomers. Furthermore, the sulfoximine group can
be readily replaced to provide dihydroisoxazoles with an
alkyl or aryl group on the C-atom of the C,N-double bond.
Elaboration of these initial results is still required:
improved cycloaddition procedures with a higher stereo-
selectivity and better overall yield need to be developed
and applied to the optically active nitrile oxide precursor.
The formation of the novel ylide 9a has been further
investigated. Heating a benzene solution of R-nitrosul-
foximine 2 and p-chlorophenyl isocyanate in the presence
of solid potassium carbonate afforded 9a in 78% yield.
R-Nitrosulfoximine 2 also underwent reaction with R-naph-
thyl isocyanate under similar conditions to afford ylide
9b in 70% yield.
Spectra of the ylides 12a ,b resembled the reported
spectra of ylides 11a -c.10 Infrared bands for the ni-
tronate group of 12a (νas 1403 cm-1 and νs 1273 cm-1
)
and of 12b (νas 1408 cm-1 and νs 1293 cm-1) are consistent
with similar values reported for ylides 11b (νas 1385 cm-1
and νs 1279 cm-1) and 11c (νas 1412 cm-1 and νs 1290
cm-1) as well as the R-nitrosulfoximine ylides 9a ,b. The
13C NMR signals at δ 99.2 for 12a and δ 99.6 for 12b
were attributed to the nitronate C-atoms, similar to the
reported values for 11a , 11b, and 11c (δ 121.5, 94.2, and
98.9, respectively) but at somewhat higher field than the
nitronate C-atoms of 9a ,b (δ 112.3 and 112.5, respec-
tively). Presumably the higher oxidation state of the
sulfoximinium ion is responsible for the lower field
chemical shift of 9a ,b.
After the observation of ylide tautomers 9a ,b as the
products of C-acylation, the question of what products
would be formed from alkylation was addressed. The
methylation of R-nitrosulfoximine 2 occurred predomi-
nantly on the nitronate C-atom rather than the nitronate
O-atom (Scheme 4). Thus, reaction of 2 in THF with
KHMDS afforded the anion, which was methylated with
excess methyl iodide. The crude product contained the
neutral C-alkylate 13 as the major product (55:45 mix-
ture of diastereomers), contaminated with a small amount
of starting 2. The starting material could not be sepa-
rated by simple chromatography (TLC or column) but
could be removed by making use of its higher kinetic
acidity.12 Unfortunately, some of the 13 (and likely also
There is a literature report8 concerning the C-acylation
of ethyl nitroacetate by p-chlorophenyl isocyanate. The
resulting product is the neutral C-acylate, nitro ester 10,
and not the ylide tautomer. However, the ylide tautomers
9a ,b rather than the neutral tautomers 8a ,b were clearly
1
formed from C-acylation of 2. The H NMR spectrum of
9a showed coupling between the N-methyl group and the
N-H (located at δ 12.04). The 13C NMR spectrum of 9a
exhibited a signal at δ 112.3 attributed to the nitronate
C-atom. Infrared spectra showed asymmetric and sym-
(9) Herman, L. W.; ApSimon, J . W. Tetrahedron Lett. 1985, 26, 1423.
(10) Hochrainer, A. Monatsh. Chem. 1966, 97, 823. Shitov, O. P.;
Kondrat’ev, V. N.; Seleznev, A. P.; Tartakovskii, V. A. Izv. Akad. Nauk
SSSR, Ser. Khim. 1976, 2, 479. Rezchikova, K. I.; Shitov, O. P.;
Tartakovskii, V. A.; Shlyapochnikov, V. A. Izv. Akad. Nauk SSSR, Ser.
Khim. 1981, 6, 1407. Bogdanov, V. S.; Semenov, V. V.; Shitov, O. P.;
Shevelev, S. A.; Burshtein, K. Ya. Izv. Akad. Nauk SSSR, Ser. Khim.
1983, 7, 1528.
(7) Pyne, S. G.; Dong, Z. J . Org. Chem. 1996, 61, 5517.
(8) Shimizu, T.; Hayashi, Y.; Ito, T.; Teramura, K. Synthesis 1986,
488.
(11) Mancuso, A. J .; Swern, D. Synthesis 1981, 3, 165.

2862 J . Org. Chem., Vol. 67, No. 9, 2002
Wade et al.
mL, 0.05 mmol) in furan (10 mL). The resulting stirred solution
was heated at 40-45 °C for 2 d. The cooled (20 °C) solution
was poured into 50 mL of aqueous 10% HOAc. Workup
afforded the crude product which was purified by flash column
chromatography (CH2Cl2/MeOH, 99:1) and subsequent pre-
parative thin-layer chromatography (EtOAc/hexanes, 50:50)
to give 0.10 g (42% yield) of 5 as an oil which was an otherwise
pure 65:35 diastereomeric mixture: 1H NMR δ 7.5-8.1 (m,
5H), 6.62 (dm, 1H min, J ) 2.6 Hz), 6.47 (dm, 1H maj, J ) 2.6
Hz), 6.0-6.1 (m, 2H), 5.37 (m, 1H min), 5.31 (dd, 1H maj, J )
1.3, 2.6 Hz), 3.00 (s, 3H maj), 2.96 (s, 3H min); HRMS (CI)
m/z calcd for C12H13N2O3S [M + H]+ 265.0647, found 265.0655.
Further preparative thin-layer chromatography (CH2Cl2/
MeOH, 98:2) afforded enriched fractions of the diastereo-
mers: 70:30 (top half of the band) and 45:55 (bottom half of
the band).
Con ver sion of Dih yd r ofu r oisoxa zole 5 to cis-3a ,6a -
Dih yd r o-3-p h en ylfu r o[2,3-d ]isoxa zole (6a ). A solution of
PhLi (1.8 M in cyclohexanes/ether, 0.41 mL, 0.68 mmol) was
added dropwise to a cold solution (-75 to -78 °C) of dihydro-
furoisoxazole 5 (78 mg, 0.29 mmol) in THF (25 mL). The
resulting cold solution was stirred for 30 min and poured into
water, and 5% HCl (20 mL) was added. Further workup
afforded the crude product which was purified by preparative
thin-layer chromatography (EtOAc/hexanes, 20:80 elution)
followed by a second preparative thin-layer chromatography
(benzene elution) to afford 26 mg (48% yield) of 6a , the more
mobile fraction, as an oil. The spectra (1H NMR, IR, 13C NMR)
matched reported spectra14 for 6a . The oil crystallized very
slowly and only when pure: mp 44-46 °C (lit.14b mp 45-46
°C).
Sch em e 4
2) underwent hydrolysis to N-methylbenzenesulfonamide
during the extraction. The new contaminants were,
however, readily removed by chromatography to afford
pure 13. It would seem that base readily attacks the
S-atom of R-nitrosulfoximines with ensuing fragmenta-
tion. However, a catalytic quantity (5 mol %) of triethyl-
amine neither destroyed nor racemized a sample of
optically active R-nitrosulfoximine 2. Chloroform solu-
tions of optically active 2 also developed N-methylben-
zenesulfonamide over time, indicative of slow acid-
catalyzed hydrolysis.
Exp er im en ta l Section
Gen er a l P r oced u r es. NMR spectra (250 MHz for 1H in
CDCl3 unless otherwise noted) were obtained as previously
described.13 Microanalyses were performed at the microana-
lytical facility, Department of Chemistry, University of Penn-
sylvania. N,S-Dimethyl-S-phenylsulfoximine (1) was prepared
from S-methyl-S-phenylsulfoximine according to the reported
method of J ohnson et al.1 Resolution of racemic S-methyl-S-
phenylsulfoximine was accomplished using the method of
Brandt and Gais.3 All reactions were run under nitrogen and
were routinely worked up by extracting with CH2Cl2 (three
25 mL portions), washing of the combined organic layers with
water (three 50 mL portions), drying over anhydrous Na2SO4,
filtering, and concentrating under reduced pressure. Flash
chromatography was carried out using 30 g portions of silica
gel.
Con ver sion of Dih yd r ofu r oisoxa zole 5 to cis-3a ,6a -
Dih yd r o-3-m eth ylfu r o[2,3-d ]isoxa zole (6b). 6b was pre-
pared in 54% yield similarly to 6a using MeLi rather than PhLi
and purification by preparative thin-layer chromatography
(CH2Cl2/MeOH, 99:1 elution). The spectra (1H NMR, IR, 13C
NMR) matched reported spectra14a except that the literature
1H NMR value attributable to the methyl group (δ 1.3) was
found to actually be δ 2.09, consistent with other related
3-methyl-4,5-dihydroisoxazoles (e.g., δ 1.98 for 5-butyl-3-
methyl-4,5-dihydroisoxazole15). Also isolated was N-methyl-
benzenesulfinamide16 (6.3 mg), obtained from the least mobile
phase of the first chromatography.
P r ep a r a tion of (+)-N-Meth yl-S-(n itr om eth yl)-S-p h en -
ylsu lfoxim in e (2). A 0.5 M toluene solution of KHMDS (16.1
mL, 8.1 mmol of KHMDS) was added to a cold (dry ice) solution
of (-)-sulfoximine 1 (0.54 g, 3.2 mmol) in THF (20 mL). The
resulting solution was allowed to warm to -40 °C and was
stirred for 30 min. A second solution containing isobutyl nitrate
(1.3 mL, 10.8 mmol) in THF (5 mL) was then added dropwise
over 1 h. The resulting solution was stirred for 6 h at -35 to
-40 °C and was subsequently poured into aqueous 10% HOAc
(100 mL). Workup afforded an oil which was purified by flash
column chromatography (CH2Cl2 and then 99:1 CH2Cl2/MeOH
elution) to give pure 2 (0.60 g, 87% yield) as an amber oil:
[R]25 +32.73° (c 3.0, MeOH); [R]25 +53.07° (c 0.98, CHCl3).
P r ep a r a tion of Ylid e 9b. A stirred mixture containing
R-nitrosulfoximine 2 (0.086 g, 0.40 mmol), 1-naphthyl isocy-
anate (0.068 g, 0.40 mmol), anhydrous K2CO3 (0.056 g, 0.40
mmol), and benzene (10 mL) was heated at reflux for 12 h.
Solids were filtered from the cooled mixture and washed with
CH2Cl2. The combined organic layers were further worked up,
giving an oil which was purified by flash column chromatog-
raphy to afford 0.14 g of crystals from the most mobile
fractions. Recrystallization from EtOH afforded 0.11 g (70%
yield) of 9b as a yellow crystalline solid: mp 149-151 °C dec;
IR (KBr) 3237 (NsH), 1619 (CdO) 1559 (amide II), 1418
(νas(nitronate)), and 1318 (νs(nitronate)) cm-1; 1H NMR δ 12.39
(br q, 1H, J ) 4.8 Hz), 11.75 (br s, 1H), 7.5-8.1 (m, 12H), 2.69
(d, 3H, J ) 4.8 Hz); 13C NMR δ 161.1, 135.1, 134.4, 134.1,
131.8, 129.5, 129.4, 128.6, 127.5, 126.8, 126.3,126.2, 125.5,
121.4, 121.1, 112.5, 25.5; HRMS (M + Na+) m/z calcd for
D
D
Prepared in a similar fashion was (-)-2: [R]25 -52.92° (c
D
0.98, CHCl3).
Prepared in a similar fashion was (()-2: IR (film) 1554
(νas(NO2)), 1358 (νs(NO2)), 1273 (νas(NdSdO)), and 1152
C
19H17N3O4SNa 406.0837, found 406.0852.
(νs(NdSdO)) cm-1 1H NMR (0.06 M in CDCl3) δ 7.56-8.00
;
Anal. Calcd for C17H17N3O4S: C, 59.52; H, 4.47; N, 10.96.
Found: C, 59.72; H, 4.51; N, 10.90.
(m, 5H), 5.70 (d, 1H, J ) 11.1 Hz), 5.60 (d, 1H, J ) 11.1 Hz),
3.04 (s, 3H); 13C NMR δ 135.5, 134.4, 129.4, 129.1, 88.0, 29.4;
P r ep a r a tion of Ylid e 9a . Ylide 9a was obtained in 78%
yield following the procedure used for the preparation of 9b
except that p-chlorophenyl isocyanate replaced 1-naphthyl
isocyanate: mp 149-149.5 °C; IR (KBr) 3259 (NsH), 1605 (Cd
O) 1513 (amide II), 1425 (νas(nitronate)), and 1327 (νs(ni-
+
MS (CI) m/z 215 [M + H]
.
Anal. Calcd for C8H10N2O3S: C, 44.85; H, 4.70; N, 13.08.
Found: C, 44.71; H, 4.90; N, 13.09.
F or m a tion of Dih yd r ofu r oisoxa zole 5. A solution of
4-chlorophenyl isocyanate (0.35 g, 2.25 mmol) in furan (2 mL)
was added dropwise over 5 min to a solution of (()-R-
nitrosulfoximine 2 (0.19 g, 0.90 mmol) and triethylamine (6
(14) (a) J aeger, V.; Mueller, I. Tetrahedron 1985, 41, 3519. (b)
Caramella, P.; Cellerino, G.; Corsico Coda, A.; Gamba Invernizzi, A.;
Gruenanger, P.; Houk, K. N.; Marinone Albini, F. J . Org. Chem. 1976,
41, 3349.
(15) Curran, D. P. J . Am. Chem. Soc. 1983, 105, 5826.
(16) J ohnson, C. R.; J onsson, E. U.; Wambsgans, A. J . Org. Chem.
1979, 44, 2061.
(12) Wade, P. A.; Hinney, H. R.; Amin, N. V.; Vail, P. D.; Morrow,
S. D.; Hardinger, S. A.; Saft, M. S. J . Org. Chem. 1981, 46, 765.
(13) Wade, P. A.; Kondracki, P. A.; Carroll, P. J . J . Am. Chem. Soc.
1991, 113, 8807.

Preparation of R-Nitrosulfoximines
J . Org. Chem., Vol. 67, No. 9, 2002 2863
1
tronate)) cm-1; H NMR δ 12.04 (br q, 1H, J ) 4.8 Hz), 11.25
into 50 mL of aqueous 10% HCl, and the mixture was worked
up to afford the crude product, containing a small portion of
starting material 2, which was dissolved in CH2Cl2 (50 mL).
Rapid extraction with 5% aqueous NaHCO3 (50 mL) removed
most of the 2 that could be recovered by acidification of the
aqueous layer with 5% HCl followed by further workup. The
organic layer contained mostly 13. Three iterations of this
procedure as previously reported for 1-(phenylsulfonyl)-1-
nitroethane10 afforded 10 mg of recovered starting R-nitrosul-
foximine 2 and 13 free of 2 but contaminated by N-methyl-
benzenesulfonamide, apparently formed from hydrolysis of 13
during the purification. Thin-layer chromatography afforded
0.04 g (44% yield) of an oil which was pure 13, a 57:43 mixture
of two diastereomers: IR (film) 1549 (νas(NO2)), 1343 (νs(NO2)),
(br s, 1H), 7.5-8.0 (m, 5H), 7.41 (dm, 2H, J ) 8.8 Hz), 7.25
(dm, 2H, J ) 8.8 Hz), 2.61 (d, 3H, J ) 4.8 Hz); 13C NMR δ
160.5, 135.4, 135.0, 134.5, 130.1, 129.5, 129.3, 129.1, 122.7,
112.3, 25.5; HRMS (FAB, M + H+) m/z calcd for C15H15N3O4-
S35Cl 368.0472, found 368.0464.
Anal. Calcd for C15H14N3O4SCl: C, 48.98; H, 3.84; N, 11.42.
Found: C, 49.03; H, 3.68; N, 11.48.
P r ep a r a tion of Ylid e 12a . A solution of anhydrous DMSO
(1.1 mL, 15.24 mmol) in CH2Cl2 (12 mL) was added dropwise
to a cold (dry ice) solution of 98% oxalyl chloride (0.44 mL,
5.08 mmol) in CH2Cl2 (12 mL). The resulting solution was
allowed to stir for 1 min, and a solution of (phenylsulfonyl)-
nitromethane (0.51 g, 2.54 mmol) and pyridine (0.51 mL, 6.35
mmol) in CH2Cl2 (12 mL) was added dropwise over a 15 min
period. Stirring was continued for an additional 15 min, and
the cold reaction solution was poured into ice/water (100 mL).
Extraction with CH2Cl2 (three 25 mL portions) afforded a
combined organic layer which was washed with 5% aqueous
NaOH (100 mL). Further workup of the organic layer afforded
a solid which was recrystallized from 95% EtOH to give 0.45
g (68% yield) of 12a as colorless needles: mp 184-86 °C; IR
(KBr) 1403 (νas(nitronate)),1333 (νas(SO2)), 1273 (νs(nitronate)),
1
1263 (νas(NdSdO)), and 1152 (νs(NdSdO)) cm-1; H NMR δ
7.5-7.95 (m, 5H), 5.82 (q, 1H maj, J ) 6.9 Hz), 5.71 (q, 1H
min, J ) 7.0 Hz), 3.00 (s, 3H maj), 2.97 (s, 3H min),1.83 (d,
3H min, J ) 7 Hz), 1.77 (d, 3H maj, J ) 6.9 Hz); 13C NMR δ
134.3, 132.8, 130.3. 130.2, 129.3, 129.2, 97.2, 96.3, 29.6, 29.4,
14.83, 14.78; HRMS (FAB) m/z calcd for C9H13N2O3S [M + H]+,
229.0647, found 229.0651.
Deter m in a tion of th e F ir st p Ka for r-Nitr osu lfoxim in e
2. The general procedure of Bordwell et al.17 was followed using
a Fisher Accumet AB15 pH meter equipped with a standard
Accumet 3-in-1 pH/ATC combination electrode (Ag/AgCl in-
ternal reference; Fisher catalog no. 13-620-530) to measure
pH values. Standard buffer solutions (Fisher Scientific) of pH
7.00 and 4.00 were used for calibration. (Phenylsulfonyl)-
nitromethane, nitromethane, and benzoylnitromethane were
used as control substances. In all cases, the electrode was
immersed in a blank solution of MeOH/H2O, 50:50, for 2 h or
longer prior to a pH measurement. The average pKa was
determined to be 6.30 after a recommended correction factor
of -0.10 pH unit was applied for measurements in MeOH/
H2O, 50:50.
and 1142 (νs(SO2)) cm-1 1H NMR (DMSO-d6) δ 7.5-8.0 (m,
;
5H), 3.18 (s, 6H); 13C NMR (DMSO-d6) δ 141.9, 132.8, 128.8,
127.5, 99.2, 27.5; MS (FAB) m/z (M + Na)+ 284, (M + H)+ 262.
Anal. Calcd for C9H11NO4S: C, 41.38; H, 4.21; N, 5.36.
Found: C, 41.31; H, 4.13; N, 5.31.
P r ep a r a tion of Ylid e 12b. 12b was prepared in 58% yield
similarly to 12a employing benzyl sulfoxide rather than
DMSO: mp 170-72 °C; IR (KBr) 1408 (νas(nitronate)), 1312
(νas(SO2)), 1293 (νs(nitronate)), and 1137 (νs(SO2)) cm-1 1H
;
NMR (DMSO-d6) δ 7.15-7.4 (m, 15H), 5.12 (d, 2H, J ) 11.8
Hz), 4.51 (d, 2H, J ) 11.8 Hz); 13C NMR (DMSO-d6) δ 146.5,
137.3, 135.6, 134.6, 134.5, 133.5, 132.3, 99.6, 50.9; MS (FAB)
m/z (M + Na)+ 436, (M + H)+ 414.
Anal. Calcd for C21H19NO4S: C, 60.79; H, 4.63. Found: C,
60.73; H, 4.30.
Ack n ow led gm en t. We thank Dr. J effrey Honovich
(Drexel University) for obtaining the mass spectra.
P r ep a r a tion of (()-N-Meth yl-S-(1-n itr oeth yl)-S-p h en -
ylsu lfoxim in e (13). A 0.5 M toluene solution of KHMDS (1.94
mL, 0.97 mmol of KHMDS) was added to a cold (dry ice)
solution of (()-R-nitrosulfoximine 2 (94 mg, 0.44 mmol) in THF
(10 mL). The resulting solution was allowed to warm to -40
°C and was stirred for 5 min. A solution of iodomethane (75
mg, 0.53 mmol) in THF (1 mL) was added dropwise to the first
solution over 5 min, and the resulting solution was stirred for
24 h at ambient temperature. The reaction solution was poured
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
5 and 13. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O010924K
(17) Bordwell, F. G.; Boyle, W. J .; Yee, K. C. J . Am. Chem. Soc. 1970,
92, 5926.