Asymmetric decarboxylative claisen rearrangement reactions of sulfoximine-substituted allylic tosylacetic esters

Article abstract of DOI:10.1021/jo050747d

Allylic acetate esters containing a variety of N-arylsulfonyl sulfoximines on the acetyl residue have been prepared and submitted to the decarboxylative Claisen rearrangement reaction. Rearranged products were isolated in generally good yields, and diastereoselectivities up to 82:18 have been obtained. The N-(2,4,6-triisopropylphenylsulfonyl)-S-phenyl sulfoximine moiety gave the best selectivity. The stereochemistry of the major isomer was established by X-ray crystallography. A model to explain the stereochemical course of the rearrangement is proposed.

Full text of DOI:10.1021/jo050747d

Asymmetric Decarboxylative Claisen Rearrangement Reactions of
Sulfoximine-Substituted Allylic Tosylacetic Esters
Donald Craig,*,§ Fabienne Grellepois,§ and Andrew J. P. White‡
Department of Chemistry and Department of Chemical Crystallography, Imperial College London,
South Kensington Campus, London SW7 2AZ, United Kingdom
d.craig@imperial.ac.uk
Received April 14, 2005
Allylic acetate esters containing a variety of N-arylsulfonyl sulfoximines on the acetyl residue have
been prepared and submitted to the decarboxylative Claisen rearrangement reaction. Rearranged
products were isolated in generally good yields, and diastereoselectivities up to 82:18 have been
obtained. The N-(2,4,6-triisopropylphenylsulfonyl)-S-phenyl sulfoximine moiety gave the best
selectivity. The stereochemistry of the major isomer was established by X-ray crystallography. A
model to explain the stereochemical course of the rearrangement is proposed.
SCHEME 1. Synthesis of Homoallylic Sulfones by
the Decarboxylative Claisen Rearrangement
Reaction and Proposed Mechanism3,a
Introduction
Since its discovery nearly a century ago the Claisen
rearrangement1 has become a mainstay of organic syn-
thesis. The power and versatility of this strategy-level
transformation has prompted considerable efforts to
develop variants of this [3,3]-sigmatropic rearrangement,
and several of these are now widely used to generate
regio- and stereochemically defined carbon-carbon and
carbon-heteroatom bonds.2 We recently introduced a
novel variant of the classical process, the decarboxylative
Claisen rearrangement (dCr) reaction.3 In this modified
transformation R-tosyl silylketene acetals formed in situ
from allylic tosylacetates 1 in the presence of stoichio-
metric or substoichiometric N,O-bis(trimethylsilyl)acet-
amide (BSA) and substoichiometric potassium acetate
* To whom correspondence should be addressed. Fax: +44-(0)20-
7594-5868. Phone: +44-(0)20-7594-5771.
§ Department of Chemistry.
‡ Department of Chemical Crystallography.
(1) Claisen, L. Chem. Ber. 1912, 45, 3157-3166.
(2) For reviews on Claisen and related rearrangements, see: (a)
Pereira, S.; Srebnik, M. Aldrichim. Acta 1993, 26, 17-29. (b) Enders,
D.; Knopp, M.; Schiffers, R. Tetrahedron: Asymmetry 1996, 7, 1847-
1882. (c) Ito, H.; Taguchi, T. Chem. Soc. Rev. 1999, 28, 43-50. (d) Chai,
Y.; Hong, S. P.; Lindsay, H. A.; McFarland, C.; McIntosh, M. C.
Tetrahedron 2002, 58, 2905-2928. (e) Nubbemeyer, U. Synthesis 2003,
7, 961-1008. (f) Martin Castro, A. M. Chem. Rev. 2004, 104, 2939-
3002. (g) For transition metal-catalyzed, nonregiospecific allylation of
R-arylsulfinyl esters through O f C allyl transfer, see: Hiroi, K.;
Suzuki, Y.; Kato, F.; Kyo, Y. Tetrahedron: Asymmetry 2001, 12, 37-
40. (h) For highly diastereoselective thio-Claisen rearrangement
reactions of ketene aminothioacetals, and leading references, see:
Nowaczyk, S.; Alayrac, C.; Reboul, V.; Metzner, P.; Averbuch-Pouchot,
M.-T. J. Org. Chem. 2001, 66, 7841-7848.
a Reagents and conditions: (a) BSA (0.1 or 1 equiv), KOAc (0.1
equiv), toluene, 110 °C, 15 h or microwave irradiation, 150 °C, 3
min.
undergo [3,3]-sigmatropic rearrangement followed by
acetate-induced desilylation-decarboxylation in situ to
provide homoallylic sulfones 2 (Scheme 1). The loss of
CO2 in these reactions gives the products of formal
transfer with allylic transposition of a carbon atom
substituted with a heteroatom, such that the dCr reaction
may be regarded as analogous to the 2,3-Wittig re-
arrangement.
(3) Bourgeois, D.; Craig, D.; King, N. P.; Mountford, D. M. Angew.
Chem., Int. Ed. 2005, 44, 618-621.
10.1021/jo050747d CCC: $30.25 © 2005 American Chemical Society
Published on Web 07/21/2005
J. Org. Chem. 2005, 70, 6827-6832
6827

Craig et al.
SCHEME 2. Decarboxylative Claisen
Rearrangement Reaction of
Sulfoximine-Containing Substrates
SCHEME 3. Sulfonylation of Sulfoximines 3a and
4aa
As part of our program devoted to the study of this
new [3,3]-sigmatropic rearrangement-fragmentation re-
action mode, we were keen to devise an asymmetric
version. Most of the published research on asymmetric
variants of Claisen and Ireland-Claisen rearrangements
has until now focused on reactions characterized by high
diastereoselectivity arising from the presence of chiral
substituents positioned outside but adjacent to the peri-
cyclic array,2e-h usually in the R-position with respect to
the vinylic moiety. In light of the effectiveness of the
tolylsulfonyl substituent in facilitating decarboxylation
post-rearrangement, we selected the N-arylsulfonylsul-
foximine group as a chiral sulfone surrogate in the dCr
reaction (Scheme 2). Chiral, nonracemic sulfoximines
may readily be accessed4 by resolution of racemates5 or
by oxidative imination of enantiomerically pure sulfox-
ides.6 They are optically stable under normal reaction
conditions, and combine similar or greater steric bulk and
enhanced electron-withdrawing capabilities with respect
to the analogous sulfones. In addition, we were attracted
by the prospect of being able to fine-tune diastereoselec-
tivity by varying the nitrogen substituent.
a Reagents and conditions: (a) (for 3b-d, 3f, 3g, 4b) RSO2Cl
(1 equiv), pyridine, 71-85%; (b) (for 3e) (CF3SO2)2O (1.2 equiv),
pyridine (2 equiv), CH2Cl2, 51%.11
SCHEME 4. Preparation of Sulfoximine 6a
a Reagents and conditions: (a) chloramine-T hydrate (1.4 equiv),
n-Bu4NBr (0.05 equiv), CH2Cl2, 23%; (b) RuO2‚xH2O (0.02 equiv),
NaIO4 (2 equiv), CCl4-MeCN-H2O, rt, 89%.
substituent on the stereochemical course of the reaction.
We wished also to probe the effect of differing sulfur aryl
substituents, not least because this structural motif has
rarely been modified in sulfoximine chemistry.4,6i
N-Sulfonyl derivatives 3b-g and 4b were simply
prepared by reaction of the known N-unsubstituted
parent sulfoximines 3a7 and 4a8 with the corresponding
sulfonylating reagent (Scheme 3).9 The previously un-
reported N-(4-tolylsulfonyl)sulfoximine 610 was prepared
by oxidative imination of 2-methylsulfanyl pyridine to
give the corresponding sulfilimine 5, which was then
oxidized (Scheme 4).
(i) Preparation of Racemic Sulfoximine-Substi-
tuted Acetate Esters. Carboxylation of sulfoximines12
3b-g, 4b, and 6 was carried out by metalation with
n-BuLi13 at -78 °C in anhydrous THF followed by
addition of gaseous CO2;14 acidic workup gave the corre-
sponding substituted acetic acids 7a-h (Scheme 5, Table
In this paper we describe in detail the synthesis of
small libraries of various esters 8, sulfoximine analogues
of 1, and the evaluation of their stereochemical behavior
in the dCr reaction.
Results and Discussion
A. Synthesis and [3,3]-Sigmatropic Rearrange-
ment of Racemic Sulfoximine-Containing Sub-
strates. With the aim of screening rapidly various N-
and S-substituted sulfoximines which could serve as
chiral auxiliaries in our study, initial efforts were focused
on the use of racemic R-sulfoximine-substituted acetate
allylic esters. On the basis of the proposed mechanism
of the dCr reaction of the analogous sulfone-containing
substrates,3 it was postulated that the desired rearrange-
ment-decarboxylation sequence would be feasible only
in sulfoximines in which the nitrogen atom was substi-
tuted with an electron-withdrawing sulfonyl group. In
particular, we were keen to study the influence of the
electronic and steric characteristics of the sulfonyl N-
(7) Sulfoximine 3a was prepared by oxidation of the S-methyl-S-
phenyl-N-(4-tolylsulfonyl)sulfilimine followed by desulfonylation of the
imine nitrogen; see: (a) Johnson, C. R.; Katekar, G. F. J. Am. Chem.
Soc. 1970, 92, 5753-5754. (b) For preparation of the sulfilimine by
oxidative imination of thioanisole with chloramine-T hydrate, see:
Johnson, C. R.; Mori, K.; Nakanishi, A. J. Org. Chem. 1979, 44, 2065-
2067. (c) For oxidation of sulfilimines to the corresponding sulfoximines
with RuO2/NaIO4 as oxidant, see: Veale, H. S.; Levin, J.; Swern, D.
Tetrahedron Lett. 1978, 503-506. (d) For the detosylation of S-methyl-
S-phenyl-N-(4-tolylsulfonyl)sulfoximine with H2SO4, see: Cram, D. J.;
Day, J.; Rayner, D. R.; Von Schriltz, D. M.; Duchamp, D. J.; Garwood,
D. C. J. Am. Chem. Soc. 1970, 92, 7369-7384.
(8) Sulfoximine 4b was prepared by oxidative imination of the
corresponding sulfoxide with hydrazoic acid; see: Johnson, C. R.;
Schroeck, C. W. J. Am. Chem. Soc. 1973, 95, 7418-7423.
(9) For arylsulfonylation of sulfoximines, see: Craig, D.; Geach, N.
J.; Pearson, C. J.; Slawin, A. M. Z., White, A. J. P.; Williams, D. J.
Tetrahedron 1995, 51, 6071-6098.
(4) For a review on sulfoximines, see: Reggelin, M.; Zur, C. Synthesis
2000, 1-64.
(5) For an efficient, improved resolution of S-methyl-S-phenyl
sulfoximine with (+)-10-camphorsulfonic acid, see: Brandt, J.; Gais,
H.-J. Tetrahedron: Asymmetry 1997, 8, 909-912.
(6) (a) Rayner, D. R.; Von Schriltz, D. M.; Day, J.; Cram, D. J. J.
Am. Chem. Soc. 1968, 90, 2721-2723. (b) Johnson, C. R.; Schroeck, C.
W. J. Am. Chem. Soc. 1973, 95, 7418-7423. (c) Jones, M. R.; Cram,
D. J. J. Am. Chem. Soc. 1974, 96, 2183-2190. (d) Johnson, C. R.;
Kirchhoff, R. A.; Corkins, H. G. J. Org. Chem. 1974, 39, 2458-2459.
(e) Mu¨ller, J. F. K.; Vogt, P. Tetrahedron Lett. 1998, 39, 4805-4806.
(f) Bach, T.; Ko¨rber, C. Eur. J. Org. Chem. 1999, 1033-1039. (g) Lacoˆte,
E. K.; Amtore, M.; Fensterbank, L.; Malacria, M. Synlett 2002, 116-
118. (h) Okamura, H.; Bolm, C. Org. Lett. 2004, 6, 1305-1307. (i) Cho,
G. Y.; Okamura, H.; Bolm, C. J. Org. Chem. 2005, 70, 2346-2349.
(10) Sulfoximine 5b was prepared by oxidation of the corresponding
sulfilimine. (a) For the preparation of pyridylsulfilimines, see: Fu-
rukawa, N.; Takahashi, F.; Kawai, T.; Kishimoto, K.; Ogawa, S.; Oae,
S. Phosphorus Sulfur Relat. Elem. 1983, 16, 167-180. (b) For a general
method for the conversion of sulfilimines into sulfoximines with RuO2/
NaIO4 as oxidant, see ref 7c.
(11) For details see the Supporting Information.
6828 J. Org. Chem., Vol. 70, No. 17, 2005

Sulfoximine-Substituted Allylic Tosylacetic Esters
sary for complete conversion.19 Direct formation of the
decarboxylated rearranged product 9a was observed in
all cases, with no traces of the intermediate rearranged
acid being detectable. As discussed previously,3,19 [3,3]-
sigmatropic rearrangement appears to be the rate-
determining step, followed by relatively fast decarboxy-
lation. In all cases the (RS*,R*) diastereoisomer predomin-
ated (for assignment of stereochemistry, see below); no
variation of the diastereoisomeric ratio versus time or
temperature was observed.
SCHEME 5. Carboxylation and Esterification of
Sulfoximines 3b-g, 4b, and 6a
Next, the optimized conditions (0.25 equiv of BSA, 0.1
equiv of KOAc, toluene, reflux) were applied to sulfox-
imine-containing esters 8b-h; the results of these ex-
periments are collected in Table 2.
Several trends emerge from the data collected in Table
2. For substrates containing an S-phenyl sulfoximine
group (Ar Ph, entries 1 to 6), selectivity in favor of the
(SS*,S*) diastereoisomer increases from 70:30 to 78:22
to 82:18 as the sulfoximine nitrogen substituent becomes
increasingly bulky (entries 1, 3, and 2). The presence of
an electron-withdrawing residue within the N-sulfonyl
group apparently exerts little or no effect on the diaste-
reoselectivity (entries 4-6), though substrates 8d-f
appeared to be slightly less reactive and 8d underwent
significant decomposition under the reaction conditions.
Replacement of the S-phenyl group with the more
electron-withdrawing 2-pyridyl moiety (substrate 8h)
resulted in a decrease in rate with no significant change
in diastereoselectivity (entry 8). In contrast, substrate
8g possessing a sterically highly demanding S-mesityl
group did not undergo dCr reaction after 10 h of exposure
to the standard reaction conditions (entry 7).
B. Synthesis and [3,3]-Sigmatropic Rearrange-
ment of Enantiomerically Pure N-(2,4,6-Triisopro-
pylphenylsulfonyl)-S-phenylsulfoximine Deriva-
tives. Following the identification of the N-(2,4,6-
triisopropylphenylsulfonyl)-S-phenylsulfoximine group as
the optimal chiral auxiliary in the dCr reaction, attention
was turned toward the synthesis and rearrangement
reactions of enantiomerically pure substrates possessing
a variety of allylic residues.
(i) Preparation of (+)-(SS)-S-Phenyl-N-(2,4,6-tri-
isopropylphenylsulfonyl)sulfoximinoyl Acetate Al-
lylic Esters. Esters (SS)-8b,i-n were readily prepared
as described for the racemic derivatives in two steps from
(+)-(SS)-S-methyl-S-phenyl-N-(2,4,6-triisopropylphenyl-
sulfonyl)sulfoximine (SS)-3c,20 which was obtained by
resolution of S-methyl-S-phenylsulfoximine with (+)-10-
camphorsulfonic acid5 followed by N-sulfonylation. The
syntheses of sulfoximines (SS)-8b,i-n are summarized
in Scheme 6 and Table 3.
(ii) Decarboxylative Claisen Rearrangement Re-
actions. The [3,3]-sigmatropic rearrangement of sulfox-
imines (SS)-8b,i-n was carried out with use of the
standard conditions (0.25 equiv of BSA, 0.1 equiv of
a Reagents and conditions: (a) n-BuLi (1.1 equiv), THF, -78
°C; (b) gaseous CO2; (c) acidic workup; (d) cinnamyl alcohol (1
equiv), EDCI (1 equiv), CH2Cl2, 0 °C.
TABLE 1. Synthesis of Esters 8a-h
yielda
(%)
yieldb
(%)
entry
sulfoximine
acid
ester
1
2
3
4
5
6
7
8
3b
3c
3d
3e
3f
3g
4b
6
7a
7b
7c
7d
7e
7f
79
80
52
24c
42
10c
42
61
8a
8b
8c
8d
8e
8f
79
84
58
50
57
50
49
42
7g
7h
8g
8h
a Yield after simple extractive workup. b Isolated yield. c Un-
optimized yield.
1).15 Esterification of 7a-h with cinnamyl alcohol in the
presence of coupling reagent EDCI16 provided the esters
8a-h17 (Scheme 5, Table 1).
(ii) Decarboxylative Claisen Rearrangement Re-
actions. The dCr reaction of substrate 8a (Ar Ph, R Tol)
was evaluated first. While the use of 0.25 equiv of BSA
in the presence of 0.1 equiv of KOAc in toluene under
reflux was identified as optimal (Table 2, entry 1),3 the
dCr reactions took place also under reflux in THF,
reflecting the more electron-withdrawing nature of the
sulfoximine functions with respect to the analogous
sulfones.18 However, these milder conditions required the
use of larger quantities of BSA because of significant
catalyst death during the increased reaction times neces-
(12) For the C-carboxylation of sulfoximines containing N-alkoxy-
carbonyl substituents, see: (a) Schaffner-Sabba, K.; Tomaselli, H.;
Henrici, B.; Renfroe, H. B. J. Org. Chem. 1977, 42, 952-958. (b) Bolm,
C.; Kahmann, J. D.; Moll, G. Tetrahedron Lett. 1997, 38, 1169-1172.
(c) Bolm, C.; Moll, B.; Kahmann, J. D. Chem. Eur. J. 2001, 7, 1118-
1128. (d) See ref 6i.
(13) For the metalation of N-sulfonylsulfoximines with n-BuLi and
their reaction with other electrophiles, see for example: (a) Reference
9. (b) Pyne, S. G.; Dong, Z. J. Org. Chem. 1996, 61, 5517-5522.
(14) As previously noticed by Bolm and co-workers, moisture should
be avoided; see refs 11b,c.
(15) Due to their instability, acids 7a-h were isolated by simple
extractive workup and were used rapidly without further purification.
(16) Use of EDCI in combination of DMAP or HOBt gave the esters
in lower yields. For example, esterification of 7a under these conditions
gave 8a in 62-64% yield.
(17) Esters 8a-h were stored in a freezer due to their instability
toward decarboxylation, regenerating the starting sulfoximines 3b-
g, 4b, or 6.
(18) (a) Matthews, W. S.; Bares, J. E.; Bartmess, J. E.; Bordwell, F.
G.; Cornforth, F. J.; Drucker, G. E.; Margolin, Z.; McCallum, R. J.;
McCollum, G. J.; Vanier, N. R. J. Am. Chem. Soc. 1975, 97, 7006-
7014. (b) Bordwell, F. G.; Branca, J. C.; Johnson, C. R.; Vanier, N. R.
J. Org. Chem. 1980, 45, 3884-3889.
(19) For ambient-temperature decarboxylative Claisen rearrange-
ment reactions of sulfone derivatives containing an additional electron-
withdrawing group on the R-position, see: Craig, D.; Grellepois, F. Org.
Lett. 2005, 7, 463-465.
(20) Trost, B. M.; Matsuoka, R. T. Synlett 1992, 27-30.
J. Org. Chem, Vol. 70, No. 17, 2005 6829

Craig et al.
TABLE 2. Decarboxylative Claisen Rearrangement Reaction of Racemic Sulfoximine-Substituted Esters 8a-h
sulfoximine ester 8
Ar
rearranged
yielda
(%)
drb,c
entry
R
product 9
time
2 h
1 h 30 min
8 h
7 h
8 h
15 h
10 h
18 h
(SS*,S*):(SS*,R*)d
1
2
3
4
5
6
7
8
8a
8b
8c
8d
8e
8f
Ph
tolyl
9a
9b
9c
9d
9e
9f
85
91
70:30
82:18
75:25
66:34
75:25
78:22
Ph
2,4,6-triisopropylphenyl
Ph
1-naphthyl
CF3
83
Ph
∼30e
Ph
2-CF3OC6H4
2,5-(CF3CH2O)2C6H3
tolyl
64
Ph
83
8g
8h
Mes
2-pyridyl
9g
9h
0
tolyl
∼50e
68:32
a Isolated yield. b dr diastereoisomeric ratio. c dr determined by 1H or 19F NMR. d For determination of stereochemistry, see below.
e Product contained traces of starting material or impurities; see the Supporting Information.
SCHEME 6. Preparation of Esters (SS)-8b,i-na
E-isomer (SS)-8j (entry 4). Notably, the rearrangement
of (SS)-8m derived from geraniol led to the formation of
a quaternary center with a 70:30 diastereoisomeric ratio
(entry 6). Substrate (SS)-8n was prepared as a mixture
of enantiomerically pure diastereomers from racemic
3-penten-2-ol, and its nonselective rearrangement likely
indicates the dominance of the stereochemically un-
defined allylic stereocenter over the sulfoximine group
in determining product configuration (entry 7).
C. Assignment of Stereochemistry. The major
isomer of (SS)-9i obtained from the dCr reaction re-
arrangement of (SS)-8i was unambiguously established
by X-ray crystallography to have the (SS,2S) configuration
(Figure 1).21 Taken together with similar trends in the
1H chemical shifts observed for the major and minor
components of the racemic rearranged products 9a,c-
f,h and of the enantiomerically pure products (SS)-9b and
(SS)-9i,l this allowed the assignment of the same stereo-
chemistry. Specifically, in all cases where comparison
could be made, the benzylic methine signal corresponding
to the newly formed stereocenter in the major products
appeared between 0.12 and 0.29 ppm downfield from the
corresponding signal for the minor product. However, for
products (SS)-9j and (SS)-9m, derived from alkyl-substi-
tuted allylic esters (SS)-8j,k and (SS)-8m, the chemical
shifts of the corresponding, nonbenzylic methine signals
did not allow unequivocal assignment of configuration
by simple comparison of NMR data. In the event, the
structure of the major isomer (SS)-9m was established
by X-ray crystallography21 to have the (SS,3R)22 config-
uration (Figure 2), allowing the assignment of the ster-
eochemistry of the major isomers of (SS)-9j by extrapo-
lation.
a Reagents and conditions: (a) n-BuLi (1.1 equiv), THF, -78
°C; (b) gaseous CO2; (c) acidic workup, 80% overall yield; (d) allylic
alcohol (1 equiv), EDCI (1 equiv), CH2Cl2, 0 °C.
TABLE 3. Synthesis of Esters (SS)-8b,i-n from Acid
(SS)-7b
a Racemic alcohol used; product obtained as a 1:1 mixture of
diastereoisomers.
D. Model Proposed for the Rearrangement. We
rationalize the stereochemical outcome of the dCr reac-
tions of sulfoximine-containing substrates 8 in terms of
KOAc, toluene, reflux) (Table 4). Rearranged products
(SS)-9b,i,j,l-n were isolated in good to excellent yields.
(21) The supplementary crystallographic data for the structures of
(SS,2S)-9i and (SS,3R)-9m have been deposited with the Cambridge
Crystallographic Data Centre as CCDC 268390 and 268391, respec-
tively. The absolute structure of (SS,2S)-9i was unambiguously deter-
mined from the X-ray data (see the Supporting Information); for
(SS,3R)-9m only the relative stereochemistry could be determined with
certainty.
(22) The (SS,3R) configuration in the products of dCr reactions of
substrates derived from alkyl-substituted allylic alcohols corresponds
to the same sense of asymmetric induction as the (SS,2S) configuration
in the aryl-substituted products because of the change in priority of
substituents on the stereocenter.
The rearrangement of compounds (SS)-8b,i and (SS)-
8l derived from allylic esters containing a terminal aryl
substituent gave the corresponding rearranged com-
pounds (SS)-9b,i,l with good diastereoselectivities (re-
spectively 82:18, 78:22, and 75:25) (entries 1, 2, and 5).
However, the alkyl-substituted Z-substrate (SS)-8k showed
the highest diastereoisomeric excess (13:87, entry 4);
here, the major isomer was identical with the minor
isomer obtained in the dCr reaction of the corresponding
6830 J. Org. Chem., Vol. 70, No. 17, 2005

Sulfoximine-Substituted Allylic Tosylacetic Esters
TABLE 4. Decarboxylative Claisen Rearrangement Reaction of Chiral Sulfoximine-Substituted Esters (SS)-8b,i-n
ester
(SS)-8
rearranged
product (SS)-9
timea
(h)
yieldb
(%)
entry
R1
R2
R3
R4
drc-e
1
2
3
4
5
6
7
(SS)-8b
(SS)-8i
(SS)-8j
(SS)-8k
(SS)-8l
(SS)-8m
(SS)-8n
(SS)-9b
(SS)-9i
(SS)-9j
(SS)-9j
(SS)-9l
(SS)-9m
(SS)-9n
H
H
H
Ph
1.5
9
91
65
78
67
76
84
94
82:18
78:22
75:25
87:13
75:25
70:30
53:47
H
H
H
C6H4-p-NO2
H
H
H
Me
H
H
H
n-Pr
H
Me
H
n-Pr
H
Ph
6
H
8
H
8
H
CH2-CH2-CHdC(CH3)2
Me
6
Me
8
a Reaction monitored by 1H NMR or TLC. b Isolated yield. c Diastereoisomeric ratio. d Determined by 1H NMR. e For the determination
of the stereochemistry, see below.
SCHEME 7. Proposed Pseudochair
Transition-State Model
FIGURE 1. The molecular structure of (SS,2S)-9i.
maximization of selectivity with Ar 2,4,6-triisopropylphen-
yl (Table 2, entry 2; Table 4, entry 1), and also the
enhanced selectivity for the opposite diastereoisomeric
product in the reaction of (SS)-8k (Table 4, entry 4), since
the R′-Ph interaction is maximized when the allylic
double bond has Z-configuration.
FIGURE 2. The molecular structure of one (A) of the two
independent molecules present in the crystals of (SS,3R)-9m
(see Figure S3 in the Supporting Information for the structure
of the second independent molecule, which has the same SS,3R
stereochemistry.)
Conclusion
the models depicted in Scheme 7. These depictions
assume Z-geometry for the intermediate sulfoximine-
substituted silylketene acetals formed in situ. The pre-
ferred conformation about the R-carbon-sulfur bond
positions the bulky ArSO2N group antiperiplanar to the
ketene acetal C-C double bond; this effect is maximized
with sterically demanding Ar groups. The preferred
trajectory of approach of the allylic moiety to the ketene
acetal is syn with respect to the sulfoximine oxygen atom
and anti to the phenyl group. This model explains the
In summary, we have shown that modest to good levels
of diastereoselectivity may be attained in the dCr reac-
tions of sulfoximine-substituted allylic acetate substrates.
Current studies are directed toward the development of
modified systems possessing additional electron-with-
drawing substituents on the R-position with a view to
attaining lower reaction temperatures and enhanced
selectivities. The results of these studies will be reported
in due course.
J. Org. Chem, Vol. 70, No. 17, 2005 6831

Craig et al.
29.4, 24.8, 24.7, 23.7. Anal. Calcd for C32H39NO5S2: C, 66.06;
H, 6.76; N, 2.34. Found: C, 65.93; H, 6.81; N, 2.34.
Experimental Section
General Procedure for Carboxylation of Sulfoximines.
A solution of sulfoximine in THF at -78 °C and under N2 was
treated with n-BuLi in hexanes (1.1 equiv). After the mixture
was stirred for 1 h at this temperature, dried CO2 was bubbled
through the solution for 30 min. The cooling bath was then
removed, the solution was diluted with CH2Cl2 or a solution
of hexane and ether (1:1) and hydrolyzed with water, and the
two layers were separated. The aqueous layer was acidified
with HCl until a colorless precipitate appeared. The suspen-
sion was extracted several times with CH2Cl2 or a solution of
hexane and ether (1:1), the organic layer was then dried
(MgSO4), concentrated under reduced pressure, and dried in
vacuo to give the corresponding acid, which was used in the
next step without further purification.
(+)-S-Carboxymethyl-S-phenyl-N-(2,4,6-triisopropyl-
phenylsulfonyl)sulfoximine, (SS)-7b. According to the gen-
eral procedure, a solution of (+)-(SS)-S-methyl-S-phenyl-N-
(2,4,6-triisopropylphenylsulfonyl)sulfoximine (SS)-3c (270 mg,
0.64 mmol) in THF (5 mL) reacted with n-BuLi (440 µL, 0.70
mmol, 1.1 equiv) and CO2. After workup (extraction with a
1:1 mixture of diethyl ether and hexane), (+)-S-carboxy-
methyl-S-phenyl-N-(2,4,6-triisopropylphenylsulfonyl)sulfox-
imine (SS)-7b (238 mg, 80%) was obtained as a colorless oil;
[R]20D +46.1 (c 0.76, CHCl3); 1H NMR (270 MHz, CDCl3) δ 9.22
(1H, br s, OH), 8.00 (2H, d, J ) 7.0 Hz, 2H-o SOPh), 7.68 (1H,
t, J ) 7.5 Hz, H-p SOPh), 7.55 (2H, t, J ) 7.0 Hz, 2H-m SOPh),
7.10 (2H, s, 2H-m triisopropylphenyl), 4.69 (1H, d, J ) 15.0
Hz AB system, CHaHbCO2), 4.62 (1H, d, J 15.0 Hz AB system,
CHaHbCO2), 4.32 (2H, sept, J ) 6.5 Hz, 2 CH(CH3)2-o), 2.85
(1H, sept, J ) 6.5 Hz, CH(CH3)2-para), 1.22 (6H, d, J ) 6.5
Hz, CH(CH3)2-o), 1.21 (6H, d, J ) 6.5 Hz, CH(CH3)2-o), 1.16
(6H, d, J ) 6.5 Hz, CH(CH3)2-p); 13C NMR (67.5 MHz, CDCl3)
δ 164.1, 152.2, 149.2, 135.0, 129.7, 129.6, 128.7, 127.1, 123.6,
61.9, 34.2, 29.4, 24.8, 24.6, 23.7.
General Procedure for Decarboxylative Claisen Re-
arrangement Reactions. A solution of sulfoximine ester,
N,O-bis(trimethylsilyl)acetamide (BSA) (0.25 equiv), and KOAc
(0.1 equiv) in toluene was heated at reflux under N2. After
1
completion of the reaction (reaction monitored by TLC or H
NMR), the solution was cooled to room temperature. Evapora-
tion of the solvent under reduced pressure and chromatogra-
phy on silica gel afforded the corresponding rearranged
products.
(SS,2S)-S-Phenyl-S-(2-phenylbut-3-enyl)-N-(2,4,6-triiso-
propylphenylsulfonyl)sulfoximine and (SS,2R)-S-Phenyl-
S-(2-phenylbut-3-enyl)-N-(2,4,6-triisopropylphenylsul-
fonyl)sulfoximine, (SS,2S)-9b and (SS,2R)-9b. According to
the general procedure, (+)-(SS)-S-(3-phenyl-2-propenyloxy-
carbonylmethyl)-S-phenyl-N-(2,4,6-triisopropylphenylsulfon-
yl)sulfoximine (SS)-8b (475 mg, 0.816 mmol) was reacted with
BSA (50 µL, 0.204 mmol, 0.25 equiv) and KOAc (9 mg, 0.082
mmol, 0.1 equiv) in toluene (4 mL) for 1.5 h. Chromatography
(35% EtOAc-petroleum ether) yielded (SS,S)-S-(2-phenylbut-
3-ene)-S-phenyl-N-(2,4,6-triisopropylphenylsulfonyl)sulfox-
imine (SS,2S)-9b and (SS,R)-S-(2-phenylbut-3-ene)-S-phenyl-
N-(2,4,6-triisopropylphenylsulfonyl)sulfoximine (SS,2R)-9b (420
mg, 91%, 82:18 mixture determined by 1H NMR) as a colorless
solid, Rf 0.68 (25% EtOAc-petroleum ether); 1H NMR (400
MHz, toluene-d8) δ 7.48 (d, J ) 7.5 Hz, 2H-o SOPh major
isomer), 7.41 (d, J ) 7.5 Hz, 2H-o SOPh minor isomer), 6.95-
6.50 (10H, m, H aromatic), 5.55 (ddd, J ) 7.0, 10.0, 17.0 Hz,
CHdCH2 major isomer), 5.50 (ddd, J ) 6.5, 13.5, 17.0 Hz, CHd
CH2 minor isomer), 4.86 (sept, J ) 6.5 Hz, 2 CH(CH3)2-o major
isomer), 4.70 (m, CHdCH2 minor isomer), 4.68 (m, CHd
CHaHb major isomer), 4.66 (d, J ) 17.0 Hz, CHdCHaHb
major isomer), 4.20 (m, 2 CH(CH3)2-o minor isomer), 4.08 (dd,
J ) 6.0, 15.0 Hz, SOCHaHb minor isomer), 4.01 (dd, J ) 6.5,
13.5 Hz, CH-Ph major isomer), 3.81 (dd, J ) 6.0, 14.5 Hz AB
system, SOCHaHb major isomer), 3.76 (m, CH-Ph minor
isomer), 3.66 (dd, J ) 7.0, 14.5 Hz AB system, SOCHaHb
major isomer), 3.54 (dd, J ) 7.5, 14.5 Hz, SOCHaHb minor
isomer), 2.60 (1H, m, CH(CH3)2-p), 1.37 (d, J ) 6.5 Hz, CH-
(CH3)2-o major isomer), 1.36 (d, J ) 6.5 Hz, CH(CH3)2-o minor
isomer), 1.29 (d, J ) 6.5 Hz, CH(CH3)2-o major isomer), 1.20
(d, J ) 6.5 Hz, CH(CH3)2-o minor isomer), 1.06 (6H, m, CH-
(CH3)2-p); 13C NMR (100 MHz, toluene-d8) δ 151.8 (C-p
triisopropylphenyl), 149.6 (2C-o triisopropylphenyl), 140.1 and
140.0, 138.8 and 138.5 (CHdCH2), 133.3 and 133.2, 129.2,
128.8, 128.7, 128.4, 128.1, 123.5, 116.3, and 116.2 (CHdCH2),
62.9 and 62.5 (SOCH2), 45.3 and 44.8 (CH-Ph), 34.5 (CH-
(CH3)2-p), 29.7 and 29.4 (2CH(CH3)2-o), 25.1 and 25.0 and 23.8
(3CH(CH3)2); MS (CI) m/z 555 [M + NH4]+, 538 [M + H]+;
HMRS (CI) m/z calcd for [C31H39NO3S2 + H]+ 538.2450, found
538.2451. Anal. Calcd for C31H39NO3S2: C, 69.24; H, 7.31; N,
2.60. Found: C, 69.32; H, 7.06; N, 2.42.
General Procedure for Esterification Reactions. A
solution of acid, allylic alcohol (1 equiv), and 1-(3-dimethyl-
aminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (1
equiv) in CH2Cl2 was stirred for 1 h at 0 °C and 15 h at room
temperature under N2. The solution was then diluted with
CH2Cl2, washed with water, and dried (MgSO4). Evaporation
of the solvent under reduced pressure and chromatography
on silica gel afforded the corresponding ester.
(+)-(SS)-S-(3-Phenyl-2-propenyloxycarbonylmethyl)-
S-phenyl-N-(2,4,6-triisopropylphenylsulfonyl)sulfox-
imine, (SS)-8b. According to the general procedure, (+)-(SS)-
S-carboxymethyl-S-phenyl-N-(2,4,6-triisopropylphenylsulfon-
yl)sulfoximine (SS)-7b (610 mg, 1.31 mmol) was esterified with
cinnamyl alcohol (176 mg, 1.31 mmol, 1 equiv), and EDCI (251
mg, 1.31 mmol, 1 equiv) in CH2Cl2 (10 mL). Chromatography
(35% EtOAc-petroleum ether) yielded (+)-(SS)-S-(3-phenyl-
2-propenyloxycarbonylmethyl)-S-phenyl-N-(2,4,6-triisopropyl-
phenylsulfonyl)sulfoximine (SS)-8b (550 mg, 72%) as a colorless
oil, Rf 0.67 (33% EtOAc-petroleum ether); [R]20D +24.9 (c 1.0,
acetone); IR νCO (film) 1743 cm-1; 1H NMR (270 MHz, CDCl3)
δ 7.97 (2H, d, J ) 8.0 Hz, 2H-o SOPh), 7.60 (1H, t, J 7) .5 Hz,
H-p SOPh), 7.47 (2H, t, J ) 8.0 Hz, 2H-m SOPh), 7.32 (5H,
m, Ph), 7.13 (2H, s, 2H-m triisopropylphenyl), 6.57 (1H, d, J
) 16.0 Hz, CHdCHPh), 6.09 (1H, td, J ) 7.0, 16.0 Hz,
CH2CHdCH), 4.74 (1H, d, J ) 14.5 Hz, AB system, CHaH-
bCO2), 4.67 (2H, d, J ) 7.0 Hz. OCH2), 4.64 (1H, d, J ) 14.5
Hz AB system, CHaHbCO2), 4.39 (2H, sept, J ) 6.5 Hz, 2
CH(CH3)2-o), 2.86 (1H, sept, J ) 6.5 Hz, CH(CH3)2-p), 1.22 (6H,
d, J ) 6.5 Hz, CH(CH3)2-o), 1.21 (6H, d, J ) 6.5 Hz, CH(CH3)2-
o), 1.16 (6H, d, J ) 6.5 Hz, CH(CH3)2-p); 13C NMR (67.5 MHz,
CDCl3) δ 161.5, 152.3, 149.1, 137.5, 137.1, 136.4, 135.8, 135.7,
134.8, 129.4, 128.7, 128.5, 126.8, 123.5, 121.5, 67.0, 62.0, 34.2,
Acknowledgment. This research was supported by
the European Community Human Potential program
(Marie Curie Individual Fellowship to F.G.) under
contract number HPMT-CT-2002-02015.
Supporting Information Available: Experimental pro-
cedure, full characterization of all new compounds, and copies
of 1H, 13C, and where appropriate 19F NMR spectra for the
products of the decarboxylative Claisen rearrangement reac-
tions. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO050747D
6832 J. Org. Chem., Vol. 70, No. 17, 2005