A method for the conversion of sulfoximines to sulfones: Application to polymer-bound sulfoximines and to the synthesis of chiral sulfones

Article abstract of DOI:10.1002/(SICI)1099-0690(200004)2000:8<1457::AID-EJOC1457>3.0.CO;2-G

Reaction of N-alkyl, N-aryl, and N-H sulfoximines with m- chloroperbenzoic acid cleanly gives the corresponding sulfones in high yield. In the case of the cleavage of N-alkyl and N-arylsulfoximines, formation of the corresponding nitroso compounds as the other reaction product was proven. Starting from enantio- and diastereopure sulfoximines, a number of chiral sulfones, including the axially chiral sulfone 6 and the sulfonyl- functionalized homoallylic alcohol 8, have been prepared. Reaction of the enantiopure sulfoximine 30 with Merrifield resin gave the polymer-bound sulfoximine 32. Oxidative cleavage of 32 afforded the sulfone 16 in high yield. Deprotonation of the sulfoximine resin 32 and reaction of Li-32 with benzaldehyde and propanal furnished the β-hydroxysulfoximine resins 33a and 33b, respectively. Oxidative cleavage of 33a and 33b readily afforded the β- hydroxy sulfones 14a and 14b, respectively.

Full text of DOI:10.1002/(SICI)1099-0690(200004)2000:8<1457::AID-EJOC1457>3.0.CO;2-G

FULL PAPER
A Method for the Conversion of Sulfoximines to Sulfones: Application to
Polymer-Bound Sulfoximines and to the Synthesis of Chiral Sulfones
[a]
[a]
Jochen Hachtel and Hans-Joachim Gais*
Keywords: Sulfoximines / Oxidative cleavage / Chiral sulfones / Polymer-bound sulfoximines / Solid-phase synthesis
Reaction of N-alkyl, N-aryl, and N–H sulfoximines with m-
chloroperbenzoic acid cleanly gives the corresponding sul-
prepared. Reaction of the enantiopure sulfoximine 30 with
Merrifield resin gave the polymer-bound sulfoximine 32. Ox-
fones in high yield. In the case of the cleavage of N-alkyl and idative cleavage of 32 afforded the sulfone 16 in high yield.
N-arylsulfoximines, formation of the corresponding nitroso
compounds as the other reaction product was proven. Start-
ing from enantio- and diastereopure sulfoximines, a number
of chiral sulfones, including the axially chiral sulfone 6 and
the sulfonyl-functionalized homoallylic alcohol 8, have been
Deprotonation of the sulfoximine resin 32 and reaction of Li-
32 with benzaldehyde and propanal furnished the β-hydro-
xysulfoximine resins 33a and 33b, respectively. Oxidative
cleavage of 33a and 33b readily afforded the β-hydroxy sul-
fones 14a and 14b, respectively.
Introduction
Sulfoximines are versatile chiral reagents for asymmetric
[
1–3]
synthesis.
The sulfonimidoyl group not only frequently
provides for a high asymmetric induction, but has also an
almost unique array of synthetically attractive features of
such as nucleofugacity, basicity, nucleophilicity, carbanion
stabilization, and a favorable redox potential. Because of
this combination, application of sulfoximines to solid-phase
asymmetric synthesis would be highly interesting.[
4,5]
The
ready alkylation, acylation, sulfonylation, and silylation of
N-H sulfoximines at the N atom[
1–3]
should allow for the
synthesis of various polymer-bound sulfoximines III from
appropriately functionalized polymers I and enantiopure
N–H sulfoximines II (Scheme 1). Deprotonation of sulfoxi-
mine III at the α-position and a subsequent functionaliz-
ation would lead to the polymer-bound modified sulfoxim-
ine IV. Because of the nucleofugacity and the redox poten-
tial of the sulfonimidoyl group,[
1–3]
Scheme 1. Conversion of sulfoximines into sulfones and application
of polymer-bound sulfoximines to solid-phase synthesis.
cleavage of IV to the
sulfoximine-free chiral compounds V and VI by substitu-
tion and reduction, respectively, can be envisioned.[
addition to the substitution and reduction of sulfoximines,
1–3]
In Results and Discussion
the development of a method for their quantitative conver- Solution-Phase Oxidative Cleavage of Sulfoximines
sion into the corresponding sulfones (VIII Ǟ IX) would be
The N-methylsulfonimidoyl functionalized alcohols 1a
highly attractive. This should not only allow for a rapid off-
and 1b were prepared by successive treatment of vinylic sul-
bead analysis of the modified polymer-bound sulfoximines
foximine 3[ with n-butyllithium and either propanal or
7]
(
IV Ǟ VII), and thus for an easy monitoring of the various
benzaldehyde.[ The attempted oxidation of these alcohols
with 2.0 equivalents of m-chloroperbenzoic acid in tetrahy-
drofuran, in the presence of 0.01 equivalents of aqueous 0.1
8]
synthetic steps on solid-support, but give also access to
chiral sulfones that are otherwise either inaccessible or diffi-
[
6]
cult to prepare. In this paper we describe the synthesis of
polymer-bound sulfoximines and a method for the conver-
sion of free, as well as of polymer-bound sulfoximines to the
corresponding sulfones, and its application to the solution-
phase synthesis of chiral sulfones.

hydrochloric acid, according to the method developed by
Cella et al. for the oxidation of secondary alcohols, did
not lead to the corresponding ketones, but gave the sulfones
a and 2b in 97% and 94% yield, respectively (Scheme 2).
Under the conditions employed, no elimination or isomeriz-
[9]
2
[
a]
Institut für Organische Chemie der Rheinisch-Westfälischen ation of the allylic alcohols 1a, 1b, 2a, and 2b were ob-
Technischen Hochschule Aachen,
served.
Professor-Pirlet-Straße 1, D-52056 Aachen, Germany
This serendipitous observation led us to investigate
whether the cleavage of 1a, and 1b with peracid could be
Fax: (internat.) ϩ 49(0)241/8888665
E-mail: Gais@RWTH-Aachen.de
Eur. J. Org. Chem. 2000, 1457Ϫ1465

WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0408Ϫ1457 $ 17.50ϩ.50/0
1457

J. Hachtel, H.-J. Gais
FULL PAPER
The oxidative cleavage of vinylic sulfoximines to the cor-
responding sulfones could also be extended to allylic sulfox-
imines. Treatment of the allylic sulfoximines 9[ and 11
12]
[7,13]
with m-chloroperbenzoic acid furnished the allylic sulfones
1
0 and 12, respectively, in 96% yield and 97% yield, respect-
ively (Scheme 3). Interestingly, under the reaction condi-
tions used, an epoxidation of the double bond could not be
observed either in the starting sulfoximines or in the sul-
fones.
Scheme 3. Oxidative cleavage of the allylic sulfoximines 9 and 11: (i)
2
6 4 3
.0 equiv. of m-C H CO H, 0.01 equiv. of 0.1  HCl, THF, reflux.
The oxidative cleavage of the β-hydroxysulfoximine
3,[
14,15]
which was prepared from (S)-N-methyl-S-lithiome-
1
thyl-S-phenylsulfoximine and benzaldehyde with 42% de,
also posed no problems (Scheme 4). Reaction of sulfoxim-
ine 13 with m-chloroperbenzoic acid led to a complete con-
version, and afforded the β-hydroxy sulfone 14a[ in 90%
yield, with an ee of 42%. Thus, within the limits of detec-
tion, no racemization of the secondary alcohol occurred
during the oxidative cleavage. In addition, no oxidation of
the hydroxy group and no elimination of 13 and 14a was de-
tected.
16]
Scheme 2. Oxidative cleavage of the vinylic sulfoximines 1a,b, 3, 5
6 4 3
and 7: (i) 2.0 equiv. of m-C H CO H, 0.01 equiv. of 0.1  HCl,
6 4 3
THF, reflux; (ii) 2.0 equiv. of m-C H CO H, THF, room temp.
turned into a general method for the synthesis of sulfones
from the corresponding sulfoximines. A similar treatment
of the vinylic sulfoximine 3[ with m-chloroperbenzoic acid
afforded the vinylic sulfone 4 in 98% yield. The reaction of
sulfoximine 5, which is accessible with de of 97% from tert-
butylcyclohexanone and (S)-N-methyl-S-lithiomethyl-S-
7]
Scheme 4. Oxidative cleavage of the β-hydroxysulfoximine 13: (i)
2
6 4 3
.0 equiv. of m-C H CO H, 0.01 equiv. of 0.1  HCl, THF, reflux.
[
10]
phenylsulfoximine,
ceeded equally well, and furnished the axially chiral sulfone
in 89% yield, with an ee of 97%.
Next, the oxidative cleavage of a vinylic sulfoximine car- the synthesis and application of polymer-bound sulfoxim-
with m-chloroperbenzoic acid pro-
All of the sulfoximines described so far carry a methyl
group at the N atom. It was thus of particular interest for
6
rying a homoallylic hydroxy group and a silyloxy group was ines to see whether sulfoximines carrying other substituents
investigated in order to study further the scope and limita- at the N atom were also amenable to an oxidative cleavage
tion of this method under the conditions used. Reaction of to the corresponding sulfones. First the reactivity of the
the sulfoximine 7, which was synthesized by a highly regio- N–H sulfoximines 15,[ rac-17,
17]
[18]
and 19
[19]
was studied
and diastereoselective hydroxyalkylation of titanated (S)-N- (Scheme 5).
methyl-S-crotyl-S-phenylsulfoximine with β-(tert-butyldi-
Reactions of sulfoximines 15, rac-17, and 19 (10% de)
phenylsilyl)oxypropanal,[
7,11]
with m-chloroperbenzoic acid with 2.0 equivalents of m-chloroperbenzoic acid were
afforded the vinylic sulfone 8 in 92% yield. Neither a cleav- slower than those of the N-methylsulfoximines described
age of the silyloxy group nor an oxidation of the secondary above, and after a comparable reaction time the conversion
hydroxy group of 7 or 8 was observed under these condi- of the sulfoximine to the sulfone was incomplete. However,
tions. Presently, there is no method available for the enantio- the use of 4 equivalents of m-chloroperbenzoic acid in the
selective synthesis of 8 starting from crotyl phenyl sulfone. reaction of 15, rac-17, and 19, under otherwise identical
Not unexpectedly, an epoxidation of the deactivated double conditions, saw a complete conversion of the starting mat-
[
1–3]
[20]
bonds
of either the sulfoximines 1a, 1b, 3, 5, or 7, or of erials, and the sulfones 16, 18, and 14b
(10% ee) were
the sulfones 2a, 2b, 4, 6, or 8 was not observed.
isolated in 93%, 88%, and 92% yield, respectively.
1458
Eur. J. Org. Chem. 2000, 1457Ϫ1465

A Method for the Conversion of Sulfoximines to Sulfones
FULL PAPER
acid at room temperature in tetrahydrofuran led to a 100%
conversion of the sulfoximine to the sulfone 16 (Scheme 6).
Similar results were obtained when deuterated chloroform
was used as the solvent. To confirm this result further, the
cleavage of the vinylic sulfoximine 3 was run in the absence
of water and hydrochloric on a preparative scale. Treatment
of sulfoximine 3 with 2 equivalents of m-chloroperbenzoic
acid at room temperature in tetrahydrofuran led to the
isolation of sulfone 4 in 96% yield (Scheme 2). Thus, we are
confident that the cleavage of the other sulfoximines will
work equally well in the absence of hydrochloric acid and
water under these conditions.
Because of the rapid oxidation of secondary alcohols
with m-chloroperbenzoic acid in the presence of 0.1 equiva-
H, 0.01 equiv. of 0.1  HCl, lents of aqueous hydrochloric acid, it may seem at first
glance surprising that the hydroxysulfoximines 1a, 1b, 7, 13,
Scheme 5. Oxidative cleavage of the N-H sulfoximines 15, rac-17,
and 19: (i) 4.0 equiv. of m-C
6
H
4
CO
3
THF, reflux.
and 19 reacted selectively without a concomitant oxidation
of the hydroxy groups. However, it is has been shown that
secondary alcohols react only slowly with m-chloroperben-
zoic acid in the absence of hydrochloric acid,[ and we used
only 0.01 equivalents of the acid, which is moreover neut-
ralized by the basic starting sulfoximine.
Next we were interested to see whether the oxidative
cleavage would also work with sulfoximines carrying larger
alkyl groups at the N atom. For a better comparison we
9]
[21]
started with the N-methylsulfoximine 20. Oxidative cleav-
age of 20 gave the sulfone 16 in 98% yield (Scheme 6). A
[22]
Having observed that N-alkyl and N-H sulfoximines are
readily converted into the corresponding sulfones upon re-
action with m-chloroperbenzoic acid, we wondered whether
sulfoximines carrying a sulfonyl, silyl, and acyl group at the
N atom could also be converted into the corresponding sul-
fones by this method. Sulfoximines of this type are import-
ant synthetic intermediates because of their different react-
ivity compared to the corresponding N-alkyl and N-H sul-
similar treatment of sulfoximine rac-21,
which carries a
tosyloxypropyl group at the N atom, with m-chloroperben-
zoic acid, cleanly furnished sulfone 16 in 98% yield. Next
we studied the cleavage of the N-benzylsulfoximine 22[23] as
a model compound for Merrifield resin-bound sulfoximines.
Reaction of 22 with m-chloroperbenzoic acid proceeded
cleanly, to furnish sulfone 16 in 98% yield. No oxidation of
the benzyl group of 22 was observed.
[
1–3]
foximines.
Reaction of the N-sulfonylsulfoximine rac-
[
18]
[24]
2
3,
the N-silylsulfoximines rac-24,
carbonylsulfoximine rac-25
and the N-alkoxy-
[25]
with m-chloroperbenzoic
acid did not afford the corresponding sulfones, but led to
an almost quantitative recovery of the starting materials
(
Scheme 7).
Determination of the mechanism of the cleavage of the
sulfoximines requires a knowledge about the fate of the N-
R group of the sulfoximine. Therefore, we submitted the N-
ethoxycarbonyl)methylsulfoximine 26[
25,26]
to the oxidation
(
with 2 equivalents of m-chloroperbenzoic acid in the ab-
sence of water and hydrochloric acid (cf. Scheme 7). Here,
Scheme 6. Oxidative cleavage of the N-alkylsulfoximines 20, 21 and besides the sulfone 16 (80%), the oxime 27[ was isolated
27]
2
2: (i) 2.0 equiv. of m-C
6
H
4
CO
3
H, 0.01 equiv. of 0.1  HCl, THF,
CO H, THF, room temp.
in 70% yield. Since the oxime 27 is most likely derived from
the corresponding nitroso compound, this result seemed to
reflux; (ii) 2.0 equiv. of m-C
6
H
4
3
Because of the reason given (vide supra), all of the oxid- indicate that the oxidation of 26 with m-chloroperbenzoic
ative cleavage reactions of sulfoximines described above acid affords, besides the corresponding sulfone, primarily
were carried out in the presence of 0.01 equivalents of aque- the corresponding nitroso compound. In order to isolate a
ous hydrochloric acid at reflux temperature in tetrahydrofu- nitroso compound in the oxidative cleavage of a sulfoximine
ran. It was of particular synthetic importance to see and to see whether N-arylsulfoximines are also amendable
whether water and hydrochloric acid are really required for to an oxidative cleavage we studied the N-arylsulfoximine
the oxidative cleavage to take place. Following the reaction 28.[ We were gratified to see that the treatment of sulfoxi-
of sulfoximine 20 with m-chloroperbenzoic acid by NMR mine 28 with 2 equivalents of m-chloroperbenzoic acid
spectroscopy, revealed that the oxidative cleavage works cleanly furnished sulfone 16 in 79% yield, and the nitroso
equally well in the absence of water and hydrochloric acid, dimer 29[ in 63% yield. Although the mechanism of the
even at room temperature, provided that 2 instead of 1.5 oxidative cleavage of sulfoximines is not yet known, the re-
equivalents of m-chloroperbenzoic acid are used. Thus, sults obtained with sulfoximines rac-23؊25, whose N atoms
treatment of 20 with 2 equivalents of m-chloroperbenzoic are of reduced nucleophilicity compared to N-alkyl, N-aryl,
28]
29]
Eur. J. Org. Chem. 2000, 1457Ϫ1465
1459

J. Hachtel, H.-J. Gais
FULL PAPER
lysis[33] of resin 32 revealed a 91% loading with the sulfoxi-
mine. IR spectroscopy of resin 32 showed new absorptions
–1
at 1264 and 1153 cm . These absorptions are typical for
sulfoximines[
1–3]
as shown by the IR spectrum of the N-
benzylsulfoximine 22, which features absorptions at 1258
and 1136 cm–1 for the sulfoximine group.
[34]
Scheme 7. Attempted oxidative cleavage of the N-functionalized
sulfoximines rac-23, rac-24, and rac-25, and cleavage of sulfoxim-
ines 26 and 28: (i) 2.0 equiv. of m-C
6
H
4
CO
3
H
H, 0.01 equiv. of 0.1 
CO H, THF, room
HCl, THF, reflux; (ii) 2.0 equiv. of m-C
6
4
3
temp.
and N-H sulfoximines,[1–3] together with the isolation of 27
and 29, and the necessity of using two equivalents of the
peracid for a complete conversion, allow us to make reason- Scheme 8. Synthesis and reactions of polymer-bound sulfoximines:
(
i) DME, Bu
CO H, 0.02 equiv. of 0.1  HCl, THF, room temp.; (iii) 1.4
equiv. of nBuLi, THF, Ϫ78 °C; (iv) 1.3 equiv. of PhCHO or 1.8
CO H,
4
NBr, 0 °C Ǟ room temp.; (ii) 4.3 equiv. of m-
able rationalizations. These are as follows: the sulfoximine
A is converted by the peracid to the corresponding N-oxide
C
6
H
4
3
B, that reacts with a second molecule of peracid under equiv. of EtCHO, THF, Ϫ78 °C; (v) 4.7 equiv. of m-C
H
6 4
3
0
.03 equiv. of 0.1  HCl, THF, room temp.
formation of the adduct C, and finally, the adduct C suffers
a fragmentation under formation of the sulfone, the nitroso
compound, and the acid (Figure 1).[
30,31]
The synthesis of sulfone 16 from the sulfoximine resin 32
by the oxidative cleavage posed no problems. Reaction of
2 with 4 equivalents of m-chloroperbenzoic acid afforded
3
the sulfone 16 in 97% yield. Next we studied the hydroxyal-
kylation of the polymer-bound sulfoximine 32 at the α-posi-
tion. Reaction of 32 with n-butyllithium at –78 °C in tetra-
hydrofuran readily afforded the polymer-bound lithiosul-
foximine Li-32. Treatment of Li-32 with benzaldehyde and
propanal furnished the hydroxysulfoximine resins 33a and
3
3b, respectively. IR spectroscopy of 33a and 33b clearly
showed the presence of a hydroxy group besides the sulfoxi-
mine group. The oxidative cleavage of 33a and 33b pro-
[16]
ceeded smoothly, and gave the hydroxy sulfones 14a and
14b,[ in 81% yield and 84% yield, respectively. Not sur-
prisingly, the ee values of 14a and 14b were only 26% and
Figure 1. Putative mechanism of the oxidative cleavage of sulfoxim-
ines
19]
Synthesis and Oxidative Cleavage of Polymer-Bound
Sulfoximines
2
4%. Generally, the asymmetric induction in the addition
[1–3]
of N-alkyl lithiosulfoximines to aldehydes is low.
The
Reaction of the potassium salt 30, which was prepared results obtained in the reactions of Li-20 and Li-32 with
from sulfoximine 15 and potassium hydride in dimethoxye- benzaldehyde seem to indicate that in the case of the resin-
[
23]
[32]
thane,
with the Merrifield resin 31
at room temper- bound reagent the asymmetric induction is lower. In both
ature in the presence of tetrabutylammonium bromide, af- cleavage experiments with 33a, and b, sulfone 20 was isol-
forded the sulfoximine resin 32 (Scheme 8). Elemental ana- ated as a by-product in 11% yield, indicating an incomplete
1460
Eur. J. Org. Chem. 2000, 1457Ϫ1465

A Method for the Conversion of Sulfoximines to Sulfones
deprotonation of 32 or an incomplete hydroxyalkylation of acid (15% water) (400 mg, 2 mmol) and aqueous HCl (0.15 mL of
FULL PAPER
0
.1 , 0.015 mmol) to give sulfone 2a (278 mg, 97%) as a colorless
Li-32.
2
0
1
oil. Ϫ [α]D ϭ ϩ9.74 (c ϭ 0.98, CHCl ). Ϫ H NMR (300 MHz,
3
CDCl
.48Ϫ1.85 (m, 2 H), 2.40 (dq, J ϭ 7.7 Hz, J ϭ 7.4 Hz, 2 H), 2.54
d, J ϭ 7.0 Hz, 1 H), 4.42Ϫ4.50 (m, 2 H), 6.94 (t, J ϭ 7.7 Hz, 1
3
): δ ϭ 0.80 (t, J ϭ 7.4 Hz, 3 H), 1.12 (t, J ϭ 7.4 Hz, 3 H),
1
(
Conclusion
1
3
H), 7.49Ϫ7.64 (m, 3 H), 7.85Ϫ7.90 (m, 2 H). Ϫ C NMR
N-Alkyl, N-aryl, and N-H sulfoximines are readily con-
verted in high yields into the corresponding sulfones upon
reaction with m-chloroperbenzoic acid. The method toler-
(
(
(
75 MHz, CDCl
d), 127.8 (d), 129.2 (d), 133.2 (d), 141.2 (u), 146.8 (d). Ϫ IR
CHCl
): ν˜ ϭ 2970 (br, s), 2935 (m), 2877 (m), 1460 (m), 1447 (m),
3
): δ ϭ 10.5 (d), 13.2 (d), 22.1 (u), 30.0 (u), 70.6
3
ates secondary hydroxy groups, CC double bonds, and sily- 1380 (m), 1304 (s), 1289 (s), 1239 (m), 1163 (m), 1139 (s), 1085 (s),
loxy groups. It allows for a new access to chiral sulfones 1024 (m), 988 (m), 972 (m), 757 (s), 720 (m), 690 (m), 621 (m), 599
ϩ
by using enantiopure sulfoximines as the starting materials. (s). Ϫ MS; m/z (%): 237 [M Ϫ OH] (1), 226 (13), 225 (100), 143
(
C
23), 125 (18), 83 (25), 78 (13), 77 (30), 71 (20), 57 (19). Ϫ
Sulfoximines carrying a silyl, sulfonyl, or alkoxycarbonyl
group at the N atom are inert under these conditions. The
results obtained with the polymer-bound sulfoximines 32,
H
13 18
O
3
S (254.3): calcd. C 61.39, H 7.13; found C 61.07, H 7.28.
(
E,R)-2-Phenylsulfonyl-1-phenylpent-2-en-1-ol (2b): Sulfoximine 1b
Li-32, and 33 demonstrate that the solid-phase synthesis of (185 mg, 0.6 mmol) was treated according to GP with m-chloroper-
chiral sulfones should be feasible. Most importantly, our benzoic acid (15% water) (600 mg, 3 mmol) and aqueous HCl
results point to a ready off-bead analysis of polymer-bound (0.15 mL of 0.1 , 0.015 mmol) to give sulfone 2b (167 mg, 94%)
2
0
1
as a colorless oil. Ϫ [α]
300 MHz, CDCl ): δ ϭ 1.03 (t, J ϭ 7.4 Hz, 3 H), 2.26 (qd, J ϭ
.4 Hz, J ϭ 3.4 Hz, 2 H), 5.78 (s, 1 H), 7.30Ϫ7.36 (m, 3 H),
D 3
ϭ ϩ14.6 (c ϭ 1.50, CHCl ). Ϫ H NMR
N-alkyl and N-arylsulfoximines through oxidative cleavage
to the corresponding sulfones. Further ongoing studies in
our laboratories are aiming at the utilization of polymer-
bound sulfoximines in asymmetric synthesis according to
Scheme 1.
(
7
7
3
1
3
.43Ϫ7.50 (t, J ϭ 7.7 Hz, 1 H) 7.55Ϫ7.61 (m, 2 H). Ϫ C NMR
): δ ϭ 12.8 (d), 22.2 (u), 69.0 (d), 125.5 (d), 127.4
d), 127.7 (d), 128.2 (d), 129.0 (d), 132.9 (d) 134.0 (u), 140.6 (u),
42.5 (u), 148.4 (d). Ϫ GC: R
ϭ 12.39. – IR (KBr): ν˜ ϭ 3500 (s,
(
(
75 MHz, CDCl
3
1
t
br), 2970 (m), 2935 (m), 2876 (m), 1637 (m), 1603 (m), 1585 (m),
1494 (m), 1448 (s), 1304 (s), 1159 (s), 1139 (s), 1086 (s), 1048 (m),
Experimental Section
1
027 (m), 1001 (m), 976 (m), 914 (m), 751 (s), 734 (s), 689 (s), 647
General: H and 13C NMR spectra were recorded on a Varian VXR
1
(m), 623 (m), 588 (m), 575 (m), 547 (m). Ϫ MS; m/z (%) ϭ 301
ϩ
3
3
00, a Varian Gemini 300, a Varian Inova 500 and a Bruker AC-
[M Ϫ 1] (1), 284 (35), 283 (11), 159 (17), 143 (51), 142 (38), 141
1
00 spectrometer. Chemical shifts are reported relative to TMS ( H,
(34), 131 (25), 128 (100), 115 (42), 106 (30), 105 (56), 91 (22), 77
1
3
1
C). Splitting patterns in the H-NMR spectra are designated as
(55), 71 (11), 57 (11), 55 (72). Ϫ C H O S (302.4): calcd. C 67.52,
1
7
18
3
s, singlet; d, doublet; dd, double doublet; t, triplet; q, quadruplet;
H 6.00; found C 67.93, H 6.19.
quin, quintet; sext, sextet; sept, septet; h, heptet; o, octet; m, mul-
tiplet. Peaks in the 13C-NMR spectra are denoted as ‘‘u’’ for car-
(E)-But-1-enyl Phenyl Sulfone (4): Sulfoximine 3 (418 mg, 2 mmol)
was treated according to GP with m-chloroperbenzoic acid (15%
bons with zero or two attached protons or ‘‘d’’ for carbons with
one or three attached protons, as determined from APT pulse se-
quence. NMR chemical shifts of minor isomers obtained as mix-
ture with major isomers are given only when an unequivocal assign-
ment was possible. – GC analyses were performed by using a
Chrompack CP-9000 instrument (DB-5: 30 m, 0.32 mm). – Melting
points were determined on a Büchi apparatus and are uncorrec-
ted. – Optical rotations were measured on a Perkin–Elmer 241 po-
larimeter at room temperature (ഠ20 °C). – MS spectra were re-
corded on a Varian MAT 212S (EI, 70 eV). Only decisive signals
of the MS spectra and those with an intensity higher than 10% are
listed. – Column chromatography was carried out on Merck silica
gel 60, 0.063Ϫ0.200 mm. – TLC was done with Merck silica gel 60
water) (800 mg, 4 mmol) and aqueous HCl (0.15 mL of 0.1 , 0.015
1
mmol) to give sulfone 4 (386 mg, 98%) as a colorless oil. Ϫ
NMR (300 MHz, CDCl
H
3
): δ ϭ 1.06 (t, J ϭ 7.4 Hz, 3 H), 2.25 (qdd,
J ϭ 7.4 Hz, J ϭ 6.1 Hz, J ϭ 1.7 Hz, 2 H), 6.34 (dt, J ϭ 15.1 Hz,
J ϭ 1.7 Hz, 1 H), 7.03 (dt, J ϭ 15.1 Hz, J ϭ 6.1 Hz, 1 H), 7.5Ϫ7.64
1
3
(
m, 3 H), 7.85Ϫ7.92 (m, 2 H). Ϫ C NMR (75 MHz, CDCl
3
): δ ϭ
1
1.7 (d), 24.8 (u), 127.6 (d), 128.7 (d), 129.8 (d), 133.3 (d), 140.8
(
(
(
u), 148.6 (d). Ϫ IR (KBr): ν˜ ϭ 2971 (w), 2937 (m), 2878 (m), 1625
w), 1447 (m), 1385 (m), 1318 (s), 1307 (s), 1287 (m), 1147 (s), 1087
ϩ
m), 754 (m), 689 (m), 589 (m), 551 (m). Ϫ MS; m/z (%): 198 [M
ϩ
ϩ
ϩ 2] (2), 197 [M ϩ 1] (4), 196 [M ] (26), 129 (14), 126 (56), 125
62), 94 (19), 78 (34), 77 (37), 55 (100). Ϫ C10 S (196.3): calcd.
C 61.20, H 6.16; found C 61.05, H 5.82.
(
12 2
H O
F254 plates. – Elementary analyses were carried out by the microan-
alytical laboratories of the Institut für Organische Chemie at the
RWTH Aachen.
(
aS)-(4-tert-Butylcyclohexylidene)methyl Phenyl Sulfone: Sulfoxim-
ine 5 (610 mg, 2 mmol, 97% de) was treated according to GP with
m-chloroperbenzoic acid (15% water) (800 mg, 4 mmol) and aque-
ous HCl (0.15 mL of 0.1 , 0.015 mmol) to give sulfone 6 (520 mg,
General Procedure for the Conversion of Sulfoximines into Sulfones
(GP): To a solution of the sulfoximine (2 mmol) and m-chloroper-
8
9%) with 97% ee [HPLC, Chiracel-OD-H, Daicel, n-heptane/2-
propanol, 98:2, R (aR) ϭ 16.2, R (aS) ϭ 16.9] as a colorless oil. –
ϭ ϩ42.8 (c ϭ 1.01, CHCl ). Ϫ H NMR (300 MHz, CDCl
δ ϭ 0.83 (s, 9 H), 0.96Ϫ1.3 (m, 3 H), 1.80Ϫ1.88 (m, 1 H),
benzoic acid (15% water) (800 mg, 4 mmol) in THF (8 mL), aque-
ous HCl (0.15 mL of 0.1 , 0.015 mmol) was added. After heating
the mixture for 8 h to reflux, it was cooled to room temperature,
treated with NaOH (10 mL of 1 , 10 mmol) and extracted with
diethyl ether (4 ϫ 20 mL). The combined organic phases were dried
t
t
2
0
1
[α]
D
3
3
):
1
3
(
.89Ϫ1.99 (m, 2 H), 2.02Ϫ2.21 (m, 1 H), 2.23Ϫ2.32 (m, 1 H),
.66Ϫ3.78 (m, 1 H), 6.15 (s, 1 H), 7.50Ϫ7.63 (m, 3 H), 7.88–7.94
4
(MgSO ) and concentrated in vacuo.
1
3
m, 2 H). Ϫ C NMR (75 MHz, CDCl
3
): δ ϭ 27.6 (d), 28.2 (u),
(E,R)-4-Phenylsulfonylhept-4-en-3-ol (2a): Sulfoximine 1a (300 mg, 29.1 (u), 29.2 (u), 32.5 (u), 37.6 (u), 47.4 (d), 123.2 (d), 127.1 (d),
1.1 mmol) was treated according to GP with m-chloroperbenzoic
129.2 (d), 133.0 (d), 142.9 (u), 161.6 (u). Ϫ GC: R
t
ϭ 12.43. Ϫ IR
Eur. J. Org. Chem. 2000, 1457Ϫ1465
1461

J. Hachtel, H.-J. Gais
KBr): ν˜ ϭ 2953 (s), 2866 (m), 1624 (m), 1479 (m), 1469 (m), 1447 (m, 2 H), 7.42Ϫ7.51 (m, 2 H), 7.52Ϫ7.60 (m, 1 H), 7.75Ϫ7.84 (m,
FULL PAPER
(
(
1
3
s), 1395 (m), 1367 (m), 1339 (m), 1304 (s), 1265 (m), 1236 (m), 2 H). Ϫ C-NMR (75 MHz, CDCl
): δ ϭ 22.39 (d), 26.99 (d),
3
1
7
149 (s), 1087 (m), 1071 (m), 858 (m), 822 (m), 797 (m), 748 (m), 55.40 (u), 112.81 (d), 146.36 (d), 128.64 (d), 129.07 (d), 133.72 (d),
ϩ
20 (m), 689 (m), 596 (s). Ϫ MS; m/z (%): 294 [M ϩ 2] (2), 293 134.70 (u). Ϫ GC: R
t
ϭ 9.11. Ϫ IR (KBr): ν˜ ϭ 2960 (m), 2929 (m),
ϩ
ϩ
[M
ϩ 1] (7), 292 [M ] (26), 226 (14), 169 (14), 151 (34), 150 (31),
43 (16), 142 (12), 109 (12), 95 (67), 94 (31), 91 (15), 81 (24), 79 974 (m), 739 (s), 690 (m), 532 (m). Ϫ MS; m/z (%) ϭ 225 [M
S (292.4): calcd. 1] (0.13), 147 (0.14), 83 (34), 82 (46), 77 (20), 67 (13), 55 (100), 51
2871 (m), 1466 (m), 1447 (m), 1319 (s), 1308 (s), 1146 (s), 1087 (m),
ϩ
1
ϩ
(29), 77 (24), 69 (10), 67 (10), 57 (100). Ϫ C17
H
24
O
2
C 69.82, H 8.27; found C 69.71, H 8.41.
16 2
(18). Ϫ C12H O S (224.3): calcd. C 64.25, H 7.19; found C 64.03,
H 7.04.
(Z,3S,4R)-1-(tert-Butyldiphenylsilyloxy)-4-methyl-6-phenylsulfonyl-
hex-5-en-3-ol (8): Sulfoximine 7 (56 mg, 0.2 mmol) was treated ac-
cording to GP with m-chloroperbenzoic acid (15% water) (60 mg,
(R)-2-Phenylsulfonyl-1-phenylethanol
(460 mg, 1.7 mmol) (mixture of diastereomers in a ratio of 71:29)
(14a): Sulfoximine 13
–6
0
.3 mmol) and aqueous HCl (0.05 mL of 0.1 , 5 ϫ 10 mmol) to was treated according to GP with m-chloroperbenzoic acid (30%
20
give sulfone 8 (50 mg, 92%) as a colorless oil. Ϫ [α]
0
1
D
ϭ Ϫ19.0 (c ϭ
water) (1.0 g, 4 mmol) and aqueous HCl (0.15 mL of 0.1 ,
1
.51, CHCl
3
). Ϫ H NMR (400 MHz, CDCl
3
): δ ϭ 1.04 (s, 9 H), 0.015 mmol). Workup as described above and purification of the
.08 (d, J ϭ 6.9 Hz, 3 H), 1.61Ϫ1.67 (m, 2 H), 3.50Ϫ3.54 (s, br, 1 colorless solid by chromatography (silica gel, ethyl acetate/pentane,
H), 3.57–3.67 (m, 1 H), 3.8Ϫ3.89 (m, 3 H), 6.36 (d, J ϭ 11.3 Hz, 1:2) gave 14a (396 mg, 90%) (42% ee) as a colorless solid. – M.p.
2
0
1
1
H), 6.44 (dd, J ϭ 11.3 Hz, J ϭ 10.7 Hz, 1 H), 7.37Ϫ7.46 (m, 7
104 °C. Ϫ [α]
): δ ϭ 3.34 (dd, J ϭ 14.3 Hz, J ϭ 1.7 Hz, 1 H), 3.51 (dd,
): δ ϭ 17.0 (d), J ϭ 14.3 Hz, J ϭ 10.2 Hz, 1 H), 3.67 (s, br, 1 H), 5.27 (d, br, 1
9.1 (u), 26.9 (d), 36.7 (u), 38.1 (d), 63.8 (u), 75.3 (d), 127.4 (d), H), 7.20Ϫ7.35 (m, 5 H), 7.56Ϫ7.62 (m, 2 H), 7.67Ϫ7.73 (m, 1 H)
27.9 (d), 129.3 (d), 130.0 (d), 130.0 (d), 130.3 (d), 133.4 (d), 132.7 7.92Ϫ7.97 (m, 2 H). Ϫ C NMR (100 MHz, CDCl
): ν˜ ϭ
68.7 (d), 125.9 (d), 128.2 (d), 128.6 (d), 129.0 (d), 129.7 (d), 134.4
(d), 139.4 (u), 140.8 (u). – GC: R
ϭ 15.5. – IR (KBr): ν˜ ϭ 3500
(s, br), 3033 (m), 2981 (m), 2934 (m), 2902 (m), 1496 (m), 1456 (m),
D 3
ϭ Ϫ17.8 (c ϭ 1.00, CHCl ). Ϫ H NMR (400 MHz,
H), 7.48Ϫ7.54 (m), 7.57Ϫ7.63 (m, 1 H), 7.64Ϫ7.68 (m, 3 H), CDCl
3
7
1
1
.91Ϫ7.94 (m, 2 H). Ϫ 13C NMR (100 MHz, CDCl
3
1
3
3
): δ ϭ 64.2 (u),
(u), 132.8 (u), 141.8 (u), 135.6 (d), 148.8 (d). Ϫ IR (CHCl
3
3
2
1
1
1
507 (br, m), 3070 (m), 3051 (m), 3016 (m), 2998 (m), 2960 (s),
931 (s), 2875 (s), 2858 (s), 1624 (m), 1589 (m), 1472 (s), 1462 (s),
t
447 (s), 1428 (s), 1392 (m), 1363 (m), 1306 (s), 1261 (m), 1218 (m), 1448 (s), 1393 (m), 1292 (s), 1238 (m), 1202 (m), 1168 (s), 1138 (s),
191 (m), 1177 (m), 1148 (s), 1112 (s), 1086 (s), 1040 (m), 1011 (m), 1086 (s), 1064 (s), 1026 (s), 996 (s), 922 (m), 830 (m), 786 (m), 764
000 (m), 986 (m), 940 (m), 872 (m), 823 (m), 805 (m), 755 (s), 704 (s), 745 (s), 706 (s), 683 (s), 561 (s), 538 (s). Ϫ MS; m/z (%) ϭ 262
ϩ
(
s), 689 (s), 668 (m), 648 (m), 615 (m), 590 (m), 506 (s). Ϫ MS; m/ [M ϩ 1] (3), 156 (5), 143 (7), 141 (6), 125 (7), 121 (13), 120 (100),
z (%) ϭ 451 (1), 433 (3), 374 (2), 373 (6), 323 (7), 309 (5), 291 (4), 107 (32), 105 (16), 103 (16), 91 (25), 79 (19), 78 (19), 77 (42), 51
59 (11), 234 (4), 222 (18), 199 (100), 183 (8), 181 (8), 135 (6), 126 (14). Ϫ C14 S (262.3): calcd. C 64.10, H 5.38; found C 64.10,
5), 105 (5), 93 (13), 91 (18), 77 (22), 55 (31), 51 (11). Ϫ H 5.40
SSi (508.7): calcd. C 68.47, H 7.13; found C 68.22, H
2
14 3
H O
(
29 36 4
C H O
Methyl Phenyl Sulfone (16): Sulfoximine 15 (200 mg, 1.3 mmol) was
treated according to GP with m-chloroperbenzoic acid (15% water)
(600 mg, 3 mmol) and aqueous HCl (0.15 mL of 0.1 ,
0.015 mmol). Subsequently, an additional amount of m-chloroper-
7.34.
(Cyclohex-1-enyl)methyl Phenyl Sulfone (10): Sulfoximine
9
(501 mg, 2 mmol) was treated according to GP with m-chloroper-
benzoic acid (15% water) (800 mg, 4 mmol) and aqueous HCl benzoic acid (15% water) (1.0 g, 5 mmol) was added and the mix-
(
0.15 mL of 0.1 , 0.015 mmol) to give sulfone 10 (454 mg, 96%)
ture was heated under reflux for 6 h. Workup as described above
1
1
as a colorless oil. Ϫ H NMR (300 MHz, CDCl
3
): δ ϭ 1.44Ϫ1.62 gave 16 (186 mg, 93%) as a colorless solid, m.p. 85 °C. Ϫ H NMR
(
3
m, 4 H), 1.86Ϫ1.96 (m, 2 H), 2.0Ϫ2.10 (m, 2 H), 3.45 (s, 2 H), (300 MHz, CDCl ): δ ϭ 3.06 (s, 3 H), 7.54Ϫ7.71 (m, 3 H),
1
3
3
(
.45 (s, 1 H), 7.50Ϫ7.58 (m, 2 H), 7.60Ϫ7.67 (m, 1 H), 7.83Ϫ7.88 7.90Ϫ7.98 (m, 2 H). Ϫ C NMR (75 MHz, CDCl
3
): δ ϭ 44.6 (d),
ϭ 8.24. Ϫ IR
(KBr): ν˜ ϭ 3023 (m), 3009 (m), 2927 (m), 1584 (m), 1478 (m), 1449
m, 2 H). Ϫ 13C NMR (75 MHz, CDCl
3
): δ ϭ 21.5 (u), 22.7 (u), 127.4 (d), 129.5 (d), 133.8 (d), 140.6 (u). Ϫ GC: R
t
2
1
5.7 (u), 28.7 (u), 64.9 (u), 126.1 (u), 128.6 (d), 128.9 (d), 133.0 (d),
33.6 (d), 138.6 (u). Ϫ GC: R
t
ϭ 10.43 (S 1). – IR (KBr): ν˜ ϭ 2935 (s), 1410 (m), 1329 (s), 1317 (s), 1297 (s), 1285 (s), 1146 (s), 1085
(
1
8
s), 2860 (m), 2837 (m), 1448 (m), 1407 (m), 1301 (s), 1251 (m), (s), 1071 (s) 1024 (m), 999 (m), 966 (m), 931 (m), 790 (m), 750 (s),
ϩ
ϩ
154 (s), 1140 (s), 1120 (s), 1084 (s) 1026 (m), 998 (m), 940 (m),
690 (s). Ϫ MS; m/z (%): 156 [M ϩ 1] (1.5), 155 [M ] (6), 140 (64),
S (156.2):
75 (m), 858 (m), 775 (m), 762 (m), 745 (s), 691 (s), 568 (s), 530 94 (14), 92 (100), 77 (83), 65 (23), 51 (40). Ϫ C
7 8 2
H O
ϩ
ϩ
(s), 479 (m). Ϫ MS; m/z (%) ϭ 237 [M ϩ 1] (0.21), 236 [M ] (1.6), calcd. C 53.83, H 5.16; found C 53.81, H 5.17.
1
43 (6), 95 (100), 94 (76), 93 (11), 79 (36), 77 (32), 67 (46), 55 (19). –
(
(
(E)-3,3-Dimethylbut-1-enyl Phenyl Sulfone (18): Sulfoximine rac-17
277 mg, 1.2 mmol) was treated according to GP with m-chloroper-
13 16 2
C H O
S: calcd. 236.0871, found 236.0871 (MS).
4-Methylpent-2-enyl Phenyl Sulfone (12): Sulfoximine 11 (con-
benzoic acid (15% water) (1.2 g, 6 mmol) and aqueous HCl (0.1 mL
taining 7% of the corresponding Z isomer) (500 mg, 2.1 mmol) was
treated according to GP with m-chloroperbenzoic acid (15% water)
of 0.1 , 0.01 mmol) to give 18 (246 mg, 88%) as a colorless oil. Ϫ
H NMR (300 MHz, CDCl ): δ ϭ 1.09 (s, 9 H), 6.22 (d, J ϭ
3
1
(
1.0 g, 5 mmol) and aqueous HCl (0.15 mL of 0.1 , 0.015 mmol)
15.1 Hz, 1 H), 7.00 (d, J ϭ 15.1 Hz, 1 H), 7.51Ϫ7.57 (m, 2 H),
1
3
to give sulfone 12 (460 mg, 97%) as a colorless oil admixed with
7.59Ϫ7.65 (m, 1 H), 7.86Ϫ7.90 (m, 2 H). Ϫ C NMR (75 MHz,
CDCl ): δ ϭ 28.4 (d), 34.2 (u), 126.5 (d), 127.6 (d), 129.3 (d), 133.3
(d), 140.8 (u), 156.5 (d). Ϫ GC: R
ϭ 8.98. Ϫ IR (neat): ν˜ ϭ 2963
(s), 2907 (m), 2870 (m), 1620 (m), 1477 (m), 1465 (m), 1447 (m),
m, 2 H), 7.52Ϫ7.60 (m, 1 H), 7.75Ϫ7.84 (m, 2 H). Ϫ 1 C NMR 1367 (m), 1320 (s), 1303 (s), 1294 (s), 1270 (m), 1239 (m), 1173 (m),
75 MHz, CDCl ): δ ϭ 21.8 (d), 31.2 (d), 60.2 (u), 113.4 (d), 148.59 1147 (s), 1088 (m), 1071 (m), 978 (m), 918 (m), 836 (m), 807 (m),
d), 128.7 (d), 129.0 (d), 133.6 (d), 138.3 (u). – GC: R
1
7
% of the corresponding Z-isomer. – E-12: H NMR (300 MHz,
CDCl ): δ ϭ 0.80 (d, J ϭ 6.7 Hz, 6 H), 2.16 (hd, J ϭ 6.7 Hz, J ϭ
.7 Hz, 1 H), 3.66Ϫ3.68 (m, 2 H), 5.26Ϫ5.38 (m, 2 H), 7.42Ϫ7.51
3
3
t
1
3
(
(
(
3
t
ϭ 9.20. Ϫ
): δ ϭ 0.64 (d, J ϭ 6.7 Hz, 6 H),
.64 (m, 1 H), 3.83 (dd, J ϭ 8.1 Hz, J ϭ 1.4 Hz, 2 H), 5.26Ϫ5.38
764 (m), 753 (m), 734 (m), 715 (m), 689 (m), 594 (s). Ϫ MS; m/z
1
ϩ
Z-12: H-NMR (300 MHz, CDCl
1
3
(%) ϭ 224 [M ] (1), 143 (9), 125 (24), 83 (100), 77 (17), 67 (14). Ϫ
C H
12 16
O
2
S (224.3): calcd. C 64.25, H 7.19; found C 64.09, H 7.23.
1462
Eur. J. Org. Chem. 2000, 1457Ϫ1465

A Method for the Conversion of Sulfoximines to Sulfones
FULL PAPER
(
2
S)-1-Phenylsulfonylbutan-2-ol (ent-14b): Sulfoximine 19 (450 mg,
.1 mmol) (mixture of diastereomers in a ratio of 55:45) was treated
according to GP with m-chloroperbenzoic acid (30% water) (1.4 g,
.7 mmol) and aqueous HCl (0.2 mL of 0.1 , 0.02 mmol). After
the addition of NaOH (10 mL of 1 , 10 mmol) and water (60 mL)
the solution was extracted with Et O (4 ϫ 100 mL). The organic
phase was dried with MgSO and the solvent removed in vacuo.
chloroperbenzoic acid (15% water) (800 mg, 4 mmol) and aqueous
HCl (0.15 mL of 0.1 , 0.015 mmol) to give sulfoximine rac-23
(690 mg, 100%).
5
Attempted Oxidative Cleavage of Sulfoximine rac-24: Sulfoximine
rac-24 (800 mg, 2 mmol) was treated according to GP with m-
chloroperbenzoic acid (30% water) (1.0 g, 4 mmol) and aqueous
HCl (0.15 mL of 0.1 , 0.015 mmol) to give sulfoximine rac-24
2
4
Purification of the residue by chromatography (silica gel, ethyl acet-
ate/pentane, 4:1) gave ent-14b (414 mg, 92%) (10% ee) as a colorless
(
768 mg, 96%).
oil. Ϫ [α]2
CDCl
3
(
(
(
0
ϭ ϩ1.2 (c ϭ 0.99, CHCl
). Ϫ 1H NMR (300 MHz,
D
3
Attempted Oxidative Cleavage of Sulfoximine rac-25: Sulfoximine
rac-25 (255 mg, 1 mmol) was treated according to GP with m-
.18Ϫ3.22 (m, 2 H), 3.36 (s, br, 1 H), 4.0Ϫ4.14 (m, 1 H), 7.55Ϫ7.64 chloroperbenzoic acid (30% water) (500 mg, 2 mmol) and aqueous
3
): δ ϭ 0.93 (t, J ϭ 7.7 Hz, 3 H), 1.43Ϫ1.65 (m, 2 H),
m, 2 H), 7.66Ϫ7.73 (m, 1 H), 7.92Ϫ7.97 (m, 2 H). Ϫ 1 C NMR
75 MHz, CDCl
d), 129.6 (d), 134.1 (d), 139.4 (u). Ϫ GC: R
3
HCl (0.1 mL of 0.1 , 0.01 mmol) to give sulfoximine rac-25
): δ ϭ 9.4 (d), 29.5 (u), 62.0 (u), 67.2 (d), 128.0 (250 mg, 98%).
3
t
ϭ 8.88. Ϫ IR (KBr):
Oxidative Cleavage of Sulfoximine 26: Sulfoximine 26 (241 mg,
ν˜ ϭ 3500 (m, br), 2968 (m), 2934 (m), 2879 (m), 1462 (m), 1448
(
(
Ϫ MS; m/z (%) ϭ 215 [M ϩ 1] (1), 214 [M ] (1), 213 [M Ϫ 1]
(
(
1
2
mmol) was treated with m-chloroperbenzoic acid (345 mg,
mmol) in THF (6 mL) and the mixture was stirred for 4 h at
m), 1304 (s), 1243 (m), 1146 (s), 1085 (s), 1052 (m), 1024 (m), 999
m), 980 (m), 749 (m), 689 (m), 600 (m), 572 (m), 544 (m), 531 (m).
ϩ
ϩ
ϩ
room temp. After adding phosphate buffer (10 mL, pH ϭ 7.2) the
solution was extracted with diethyl ether (3ϫ50 mL) and the com-
bined organic phases were concentrated in vacuo. Purification of
the residue by chromatography (ethyl acetate/pentane, 1:1) gave,
1), 186 (10), 185 (100), 156 (20), 143 (13), 142 (6), 141 (72), 125
9), 91 (12), 78 (20), 77 (73), 72 (23), 55 (21). Ϫ C10 S (214.3):
14 3
H O
calcd. C 56.05, H 6.59; found C 55.75, H 6.80.
besides sulfone 16 (124 mg, 80%), the oxime 27 (82 mg, 70%) as a
1
Oxidative Cleavage of Sulfoximine 20: Sulfoximine 20 (350 mg,
colorless oil. – GC: R
t
ϭ 6.73 (S2). Ϫ H NMR (400 MHz, CDCl
3
):
2
.1 mmol) was treated according to GP with m-chloroperbenzoic
δ ϭ 1.35 (t, J ϭ 7.1 Hz, 3 H), 4.32 (q, J ϭ 7.1 Hz, 2 H), 7.57 (s, 1
1
3
acid (15% water) (600 mg, 3 mmol) and aqueous HCl (0.15 mL of
3
H). Ϫ CNMR (100 MHz, CDCl ): δ ϭ 14.0 (d), 61.81 (u), 141.6
0
.1 , 0.015 mmol) to give sulfone 16 (318 mg, 98%) as a color- (d), 162.1 (u). Ϫ IR (KBr): ν˜ ϭ 3343 (br, s), 2987 (m), 1727 (s),
less solid.
1624 (m), 1448 (s), 1373 (m), 1312 (s), 1261 (m), 1211 (s), 1097 (w),
ϩ
1
8
4
035 (s), 744 (m). Ϫ MS; m/z (%): ϭ 102 (M – 15, 1), 100 (27),
9 (100), 72 (63), 71 (39), 45 (9). Ϫ C NO (117.0): calcd. C
1.03, H 6.02, N 11.96; found C 40.81, H 5.90, N 11.48.
Oxidative Cleavage of Sulfoximine rac-21: Sulfoximine rac-21
4
H
7
3
(280 mg, 0.76 mmol) was treated according to GP with m-chlorop-
erbenzoic acid (30% water) (1.0 g, 4 mmol) and aqueous HCl (6 mL
of 0.1 , 0.6 mmol) to give sulfone 16 (116 mg, 98%) as a colorless
solid. Analytic data see above.
Oxidative Cleavage of Sulfoximine 28: Sulfoximine 28 (288 mg,
1 mmol) was treated with m-chloroperbenzoic acid (345 mg,
2
mmol) in THF (6 mL) and the mixture was stirred for 6 h at room
Oxidative Cleavage of Sulfoximine 22: Sulfoximine 22 (250 mg,
temperature. During the reaction the solution adopted a green
color and a colorless participate was formed. After adding phos-
phate buffer (10 mL, pH ϭ 7.2) the solution was extracted with
1
(

mmol) was treated according to GP with m-chloroperbenzoic acid
30% water) (1.0 g, 4 mmol), THF (6 mL) and HCl (0.15 mL of 0.1
, 1.5 ϫ 10–2 mmol) to give 16 (154 mg, 98%) as a colorless solid.
CHCl
trated in vacuo. Purification of the residue by chromatography
ethyl acetate/pentane, 1:1) gave, besides sulfone 16 (121 mg, 79%),
the dimer 29 (104 mg, 63%) as a colorless solid, m.p. 154 °C. Ϫ
3
(3ϫ50 mL), and the combined organic phases were concen-
Analytic data see above.
(
Oxidative Cleavage of Sulfoximine 20 in the Absence of Water and
Hydrochloric Acid: (a) Sulfoximine 20 (42 mg, 0.24 mmol) was
1
HNMR (400 MHz, CDCl
3
): δ ϭ 3.93 (s, 3 H), 7.57Ϫ7.82,
.89Ϫ7.94 (m, 4 H). Ϫ C NMR (100 MHz, CDCl ): δ ϭ 53.1 (d),
12.3 (d), 124.9 (u), 123.0 (d), 131.2 (d), 134.4 (d), 142.1 (u), 163.6
treated with m-chloroperbenzoic acid (41 mg, 0.24 mmol) in
1
3
7
1
3
1
[D
8
]THF (1.2 mL). After 30 min a H NMR spectrum showed a
5
5% conversion of 20 to the sulfone 16. After the addition of an-
(
d). – IR (KBr): ν˜ ϭ 3029 (s), 2955 (s), 1735 (s), 1603 (s), 1580 (s),
1
other equivalent of m-chloroperbenzoic acid, the H NMR spec-
trum after 30 min showed the complete conversion of 20 to the
sulfone 16.
1
1
534 (s), 1458 (s), 1435 (s), 1352 (s), 1293 (s), 1259 (s), 1194 (s),
129 (s), 1075 (s), 960 (s), 824 (s), 791 (s), 757 (s), 700 (s). – MS;
ϩ
m/z (%): ϭ 165 (M , 100), 135 (50), 134 (20), 120 (11), 104 (21),
9
2 (50),77 (90), 76 (38), 64 (12), 63 (9), 51 (12), 50 (42). – C
8 7 3
H NO
(
b) Sulfoximine 20 (73 mg, 0.43 mmol) was treated with m-chlorop-
(
165.04): calcd. C 58.18, H 4.27, N 8.48; found C 58.07, H 4.38,
erbenzoic acid (149 mg, 0.86 mmol) in CDCl (1.3 mL). After stir-
ring the mixture at room temperature for 30 min, the H NMR
3
1
N 8.36.
spectrum showed a complete conversion of 20 to the sulfone 16.
Synthesis of the Resin Bound Sulfoximine 32: A solution of sulfoxi-
mine 15 (12 mmol, 1.86 g) in DME (20 mL) was added dropwise
at room temperature to a suspension of KH (1.6 g, 35% in mineral
oil, 14 mmol) in DME (30 mL). After the evolution of hydrogen
had ceased, the mixture was stirred at room temperature for 3 h.
After cooling the mixture to 0 °C, tert-butylammonium bromide
Oxidative Cleavage of Sulfoximine 3 in Absence of Water and Hy-
drochloric Acid: Sulfoximine 3 (209 mg, 1 mmol) was stirred at
room temperature with m-chloroperbenzoic acid (345 mg, 2 mmol)
in THF (6 mL) for 4 h. After the addition of water (10 mL) the
mixture was neutralized (pH ϭ 7) with 1  NaOH and extracted
(
300 mg) and the Merrifield resin 31 (5 g of 1.24 mmol/g, 6.2 mmol)
were added, and stirring of the mixture at room temperature was
continued for 14 h. Subsequently, aqueous NH Cl (100 mL) was
added and the resin was filtered, washed successively with water (4
ϫ 50 mL), CH Cl (4 ϫ 50 mL), ethyl acetate (4 ϫ 50 mL), and
with Et
2
O (3 ϫ 60 mL). The combined organic phases were dried
4
) and concentrated in vacuo. Sulfone 4 (189 mg, 96%) was
(MgSO
4
obtained as a colorless oil. Analytical data see above.
Attempted Oxidative Cleavage of Sulfoximine rac-23: Sulfoximine
rac-23 (690 mg, 1.8 mmol) was treated according to GP with m-
2
2
pentane (4 ϫ 50 mL), and dried in vacuo to give 32 (5.6 g). Ele-
Eur. J. Org. Chem. 2000, 1457Ϫ1465
1463

J. Hachtel, H.-J. Gais
FULL PAPER
sulfone 16 (6.3 mg, 11%) as a by-product. Ϫ [α]2
0.98, CHCl ).
0
ϭ Ϫ6.4 (c ϭ
mental analysis showed a 91% chlorine-sulfoximine exchange. Ϫ
D
C
66
H67NOS (922.3): calcd. (for a complete chlorine-sulfoximine ex-
3
change): C 85.95, H 7.32, N 1.52; found C 85.42, H 7.36, N 1.38.
Ϫ IR (KBr): ν˜ ϭ 3437 (m, br), 3081 (m), 3058 (m), 3022 (m), 2917
Oxidative Cleavage of the Sulfoximine Resin 33b: Resin 33b
500 mg, 0.48 mmol) was treated according to GP with m-chlorop-
erbenzoic acid (30% water) (500 mg, 2 mmol) and aqueous HCl
(
(
1
(
1
m), 2849 (m), 1943 (m), 1802 (m), 1720 (m), 1656 (m), 1600 (m),
583 (m), 1802 (m), 1720 (m), 1491 (s), 1447 (s), 1364 (m), 1311
m), 1264 (m, NϭSϭO), 1180 (m), 1153 (m, NϭSϭO), 1112 (m),
067 (m), 1026 (s), 963 (m), 943 (m), 905 (m), 838 (m), 745 (s), 670
s), 524 (s).
(
(
0.15 mL of 0.1 , 0.015 mmol). After the addition of NaOH
10 mL of 1 , 10 mmol) the resin was filtered and washed success-
2
ively with water (3 ϫ 60 mL) and Et O (4 ϫ 60 mL). The combined
(
organic phases were dried and concentrated in vacuo. Purification
of the residue by chromatography (silica gel, ethyl acetate/pentane,
4:1) gave sulfone 14b (85.9 mg, 84%) (24% ee) as a colorless oil and
Oxidative Cleavage of the Sulfoximine Resin 32: resin 32 (800 mg,
.75 mmol) was treated according to GP with m-chloroperbenzoic
0
2
0
acid (30% water) (800 mg, 3.2 mmol) and aqueous HCl (0.15 mL sulfone 16 (6.3 mg, 11%) as a by-product. Ϫ [α]
of 0.1 , 0.015 mmol). After the addition of NaOH (10 mL of 1
0.95, CHCl ). Analytic data see above.
, 10 mmol) the resin was filtered and washed successively with
water (3 ϫ 60 mL) and Et O (4 ϫ 60 mL). The combined organic
D
ϭ Ϫ8.2 (c ϭ
3

2
Acknowledgments
Financial support of this work by the Deutsche Forschungsgemein-
phases were dried and concentrated in vacuo. Purification of the
colorless crystalline residue by chromatography (silica gel, ethyl
acetate/pentane, 1:2) gave sulfone 16 (112 mg, 97%) as a colorless schaft [Sonderforschungsbereich ‘ ‘A symmetrische Synthese mit
solid. Ϫ GC: R
t
ϭ 8.24 (S 2). Ϫ R
f
ϭ 0.4 (ethyl acetate/pentane,
chemischen und biologischen Methoden’’ (SFB 380)] is gratefully
acknowledged.
1:2). Analytic data see above.
Hydroxyalkylation of the Sulfoximine Resin 32 with Benzaldehyde –
Synthesis of the Sulfoximine Resin 33a: a suspension of 32 (0.8 g,
[
1]
S. G. Pyne, Sulfur Reports 1992, 12, 57Ϫ93.
M. Mikołajczk, J. Drabowicz, P. Kiełbasi n´ ski, Chiral Sulfur Re-
agens, CRC Press New York 1997.
3]
[2]
0
3
.77 mmol) in THF (20 mL) was stirred at room temperature for
0 min. Subsequently, the suspension was cooled to –78 °C and
[
[
M. Reggelin, C. Zur, Synthesis, 2000, 1Ϫ64.
4] [4a]
nBuLi was added (0.7 mL of 1.6  in hexane, 1.1 mmol). After
stirring the mixture for 2 h, benzaldehyde (1 mmol, 0.1 mL) was
added. Stirring of the mixture was continued for 5 h, and water
M. Kawana, S. Emoto, Tetrahedron Lett. 1972, 13,
[4b]
4
855Ϫ4858. –
M. Kawana, S. Emoto, Bull. Chem. Soc. Jpn.
[4c]
1
974, 47, 160Ϫ165. –
A. R. Colwell, L. R. Duckwall, R.
Brooks, S. P. McManus, J. Org. Chem. 1981, 46, 3097Ϫ3102.
(10 mL) was added. The resin was filtered, washed successively with
[4d]
Ϫ
C. R. McArthur, P. M. Worster, J.-L. Jiang, C. Leznoff,
[4e]
water (3 ϫ 80 mL), CH Cl (3 ϫ 60 mL), and pentane (3 ϫ 60 mL),
2
2
Can. J. Chem. 1982, 60, 1836Ϫ1841. Ϫ
H. S. Moon, N. E.
[4f]
Schore, M. J. Kurth, J. Org. Chem. 1992, 57, 6088Ϫ6089. –
and dried in vacuo to give 33a (869 mg). Ϫ IR (KBr): ν˜ ϭ 3413 (s,
br, OH), 3082 (s), 3059 (s), 3024 (s), 2915 (s), 2848 (s), 1945 (m),
H. S. Moon, N. E. Schore, M. J. Kurth, Tetrahedron Lett. 1994,
[4g]
3
5, 8915Ϫ6918. –
A. V. Purandare, S. Natarajan, Tetrahed-
1
811 (m), 1665 (m), 1600 (s), 1583 (m), 1510 (m), 1492 (s), 1479
m), 1451 (s), 1420 (m), 1373 (m), 1355 (m), 1312 (m), 1251 (s, Nϭ
SϭO), 1220 (s), 1198 (s), 1122 (s, NϭSϭO), 1081 (s), 1068 (s), 1027
[4h]
ron Lett. 1997, 38, 8777Ϫ8780. –
S. M. Allin, S. J.
[4i]
(
Shuttleworth, Tetrahedron Lett. 1996, 37, 8023Ϫ8026. –
M.
Reggelin, V. Brenig, Tetrahedron Lett. 1996, 37, 6851Ϫ6854. Ϫ
[4j]
[4k]
K. Burggess, D. Lim, Chem. Commun. 1997, 785Ϫ786. Ϫ
(
(
s), 974 (s), 905 (m), 815 (m), 756 (s), 696 (s), 674 (s), 621 (m), 531
s), 463 (s).
C. W. Phoon, C. Abell, Tetrahedron Lett. 1998, 39, 2655Ϫ2658.
[5]
[5a]
For reviews, see:
B. J. Backes, J. A. Ellman, Curr. Opin.
[5b]
Chem. Biol. 1997, 1, 86Ϫ93. Ϫ
D. Obrecht, J. M. Villa-
Hydroxyalkylation of the Sulfoximine Resin 32 with Propanal – Syn-
thesis of Sulfoximine Resin 33b: a suspension of 32 (0.8 g,
lgordo, Solid-Supported Combinatorial and Parallel Synthesis of
Small-Molecular-Weight Compound Libraries, Pergamon Press,
Oxford 1998.
6]
0
3
.77 mmol) in THF (20 mL) was stirred at room temperature for
0 min. Subsequently, the suspension was cooled to Ϫ78 °C and
[
N. S. Simpkins, Sulphones in Organic Synthesis, Pergamon
Press, Oxford, 1993.
[7]
nBuLi was added (0.75 mL of 1.6  in hexane, 1.20 mmol). After
stirring the mixture at this temperature for 2 h, propanal (0.1 mL,
H.-J. Gais, R. Hainz, H. Müller, G. Raabe, J. Runsink, S. Nien-
stedt, M. Schleusner, J. Hachtel, R. Loo, J. Decker, P. Bruns,
N. Giesen, C.-W. Woo, Eur. J. Org. Chem. submitted.
J. Hachtel, projected Ph. D. Thesis, RWTH Aachen 2000.
J. A. Cella, J. P. McGrath, S. L. Regen, Tetrahedron Lett. 1975,
1
5
.4 mmol) was added. Stirring of the mixture was continued for
h, and water (10 mL) was added. The resin was filtered, washed
[
[
8]
9]
2 2
successively with water (3 ϫ 80 mL), CH Cl (3 ϫ 60 mL), and
pentane (3 ϫ 60 mL), and dried in vacuo to give 33b (839 mg). Ϫ
IR (KBr): ν˜ ϭ 3392 (s, br, OH), 3082 (s), 3058 (s), 3024 (s), 2916
4
7, 4115–4118.
[10]
I. Erdelmeier, H.-J. Gais, H. J. Lindner, Angew. Chem. 1986,
8, 912Ϫ914; Angew. Chem. Int. Ed. Engl. 1986, 23, 935Ϫ937.
[11]
9
(s), 2848 (s), 2376 (m), 2336 (m), 2210 (m), 1945 (m), 1872 (m),
H.-J. Gais, H. Müller, J. Decker, R. Hainz, Tetrahedron Lett.
1995, 36, 7433Ϫ7436.
1810 (m), 1656 (m), 1639 (m), 1600 (s), 1583 (m), 1510 (m), 1492
[
[
[
12]
13]
14]
(s), 1479 (s), 1444 (s), 1421 (s), 1374 (m), 1354 (m), 1311 (m), 1252
(s, NϭSϭO), 1220 (s), 1199 (s), 1121 (s, NϭSϭO), 1079 (s), 1026
(s), 976 (s), 904 (s), 804 (m), 814 (m), 744 (s), 696 (s).
H.-J. Gais, H. Müller, J. Bund, M. Scommoda, J. Brandt, G.
Raabe, J. Am. Chem. Soc. 1995, 117, 2453Ϫ2466.
R. Hainz, H.-J. Gais, G. Raabe, Tetrahedron: Asymmetry 1996,
7
, 2505Ϫ2508.
C. R. Johnson, C. J. Stark, Jr., J. Org. Chem. 1982, 47,
1
Oxidative Cleavage of the Sulfoximine Resin 33a: Resin 33a
500 mg, 0.48 mmol) was treated according to GP with m-chlorop-
erbenzoic acid (30% water) (500 mg, 2 mmol) and aqueous HCl
193Ϫ1196.
(
[15]
M. Scommoda, H.-J. Gais, S. Bosshammer, G. Raabe, J. Org.
Chem. 1996, 61, 4379Ϫ4390.
M. Node, K. Nishide, Y. Shigeta, K. Obata, H. Shiraki, H.
Kunishige, Tetrahedron 1997, 53, 12883Ϫ12894.
J. Brandt, H.-J. Gais, Tetrahedron: Asymmetry 1997, 8,
[
[
16]
17]
(
(
0.15 mL of 0.1 , 0.015 mmol). After the addition of NaOH
10 mL of 1 , 10 mmol) the resin was filtered and washed success-
2
ively with water (3 ϫ 60 mL) and Et O (4 ϫ 60 mL). The combined
organic phases were dried and concentrated in vacuo. Purification
of the residue by chromatography (silica gel, ethyl acetate/pentane,
9
09Ϫ912.
[18]
[19]
A. W. Giesen, Ph. D. Thesis, RWTH Aachen 1998.
K.-J. Hwang, E. W. Logusch, L. H. Brannigan, M. R. Thomp-
son, J. Org. Chem. 1987, 52, 3435Ϫ3441.
4:1) gave 14a (101.8 mg, 81%) (26% ee) as a colorless solid and
1464
Eur. J. Org. Chem. 2000, 1457Ϫ1465

A Method for the Conversion of Sulfoximines to Sulfones
FULL PAPER
S.-L. Huang, D. Swern, J. Org. Chem. 1979, 44, 2510Ϫ2513.
[
[
20]
21]
[30]
[31]
R. Chincilla, C. Najera, J. Pardo, M. Yus, Tetrahedron: Asym-
metry 1990, 1, 575Ϫ578.
For the formation of sulfones as by-products in the oxidation
[31a]
C. R. Johnson, C. W. Schroeck, J. Am. Chem. Soc. 1973, 95,
of sulfilimines with m-chloroperbenzoic acid, see:
T. Yoshi-
7418.
mura, T. Omata, N. Furukawa, S. Oae, J. Org. Chem. 1976, 41,
[
[
22]
23]
[31b]
S. Boßhammer, H.-J. Gais, Synthesis 1998, 919Ϫ927.
1728Ϫ1733. Ϫ
23, 421Ϫ423. –
M. D. Coburn, J. Heterocyclic Chem. 1986,
M. D. Coburn, J. Heterocyclic Chem. 1989,
[31c]
[
C. R. Johnson, O. M. Lavergne, J. Org. Chem. 1993, 58,
31d]
1922Ϫ1923.
26, 1883Ϫ1884. –
N. Gaggero, L. DЈAccolti, S. Colonna,
[
[
[
[
[
[
24]
25]
26]
27]
28]
29]
R. Curci, Tetrahedron Lett. 1997, 38, 5559Ϫ5562.
S. G. Pyne, B. Dikic, Tetrahedron Lett. 1990, 31, 5231Ϫ5234.
F. Porstmann, Ph. D. Thesis, RWTH Aachen 1999.
T. R. Williams, D. J. Cram, J. Org. Chem. 1973, 38, 20Ϫ26.
T. W. Rave, D. S. Breslow, J. Org. Chem. 1971, 36, 3813–3815.
C. Bolm, J. P. Hildebrand, J. Org. Chem. 2000, 65, 169Ϫ175.
F. J. Alway, A. B. Walker, Ber. Dtsch. Chem. Ges. 1903,
[32]
[33]
R. B. Merrifield, J. Am. Chem. Soc. 1963, 85, 2149Ϫ2154.
B. Yan, C. F. Jewell, Jr., S. W. Myers, Tetrahedron 1998, 54,
11755Ϫ11766.
[34]
M. Scommoda, Ph. D. Thesis, RWTH Aachen 1995.
Received October 12, 1999
2312Ϫ2315.
[O99562]
Eur. J. Org. Chem. 2000, 1457Ϫ1465
1465