Highly diastereoselective baldwin rearrangement of isoxazolines into cis -acylaziridines

Article abstract of DOI:10.1021/jo101273d

An atom-economical and practical synthesis of cis-N-benzenesulfonamide acylaziridines through the Baldwin rearrangement of various N-benzenesulfonamide isoxazolines has been reported. A detailed experimental study revealed the beneficial effect of microwaves and pointed out the crucial role of the temperature in the reaction course. Moderate to good yields and excellent cis stereoselectivities were achieved for 13 examples.

Full text of DOI:10.1021/jo101273d

pubs.acs.org/joc
co-workers described a rearrangement promoted by a stoichio-
Highly Diastereoselective Baldwin Rearrangement
of Isoxazolines into cis-Acylaziridines
metric amount of Co(0), leading to the corresponding N-benzyl-
substituted acylaziridine with moderate to good selectivities.4 As
part of a program aimed at developing gold and iron reactions,5
we recently described a straightforward synthesis of N-sulfonyl
2,3-dihydroisoxazoles from propargylic alcohols (Scheme 2).6
We anticipated that such compounds may undergo rearrange-
ment into N-sulfonylaziridines. To the best of our knowledge, no
systematic study on the influence of the isoxazoline substituents
on the course of the reaction has been realized and, in particular,
on the effect of a EWG, such as a sulfonyl, on the nitrogen.
Moreover, this transformation could lead to functionalized
sulfonyl aziridines, which are valuable intermediates in organic
synthesis.7 In this paper, we disclose our results on this Baldwin
rearrangement.
Eric Gayon,† Olivier Debleds,† Marie Nicouleau,†
Frederic Lamaty,‡ Arie van der Lee,§ Emmanuel Vrancken,*,†
and Jean-Marc Campagne*,†
†Institut Charles Gerhardt (ICGM), UMR 5253
CNRS-UM2-UM1-ENSCM, 8 rue de l’Ecole Normale,
34296 Montpellier Cedex 5, France, ‡Institut des Biomoleꢀcules
Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2,
Place E. Bataillon, 34095 Montpellier Cedex 5, France, and
ꢀ
§
Institut Europeen des Membranes, UMR-CNRS 5635, Place
E. Bataillon, 34085 Montpellier Cedex 5, France
emmanuel.vrancken@enscm.fr
Received June 29, 2010
We first investigated the thermal rearrangement of iso-
xazoline 2a (Ar = p-tolyl, R = n-Bu) chosen as model sub-
strate (Scheme 3). The influence of three parameters (solvent,
temperature, time) was investigated. Results are summarized
in Table 1.
The reaction gave predominantly one diastereomer, in 83/17
to >95/5 diastereomeric ratio (dr). The cis relative strereo-
chemistry of the major compound has been assigned from the
comparison of the 3J value (7.9 Hz) with previously reported
data for acylaziridine analogues.3a This assumption was further
confirmed from an X-ray analysis of product cis-3l8 (vide infra)
and is in full agreement with previously reported DFT studies
where N-sulfonylaziridines adopt a trans/trans conformation
between C and N substituents in order to minimize steric
effects.9 The 4.2 Hz 3J constant value of the minor compound
indicates a trans relationship between the C substituents.
The reaction is slow, and the diastereomeric ratio increases
with time (Table 1, entries 1-3). The polarity of the solvent
An atom-economical and practical synthesis of cis-N-
benzenesulfonamide acylaziridines through the Baldwin
rearrangement of various N-benzenesulfonamide isoxa-
zolines has been reported. A detailed experimental study
revealed the beneficial effect of microwaves and pointed
out the crucial role of the temperature in the reaction
course. Moderate to good yields and excellent cis stereo-
selectivities were achieved for 13 examples.
(4) Ishikawa, T.; Kudoh, T.; Yoshida, J.; Yasuhara, A.; Manabe, S.;
Saito, S. Org. Lett. 2002, 4, 1907–1910.
(5) (a) Georgy, M.; Boucard, V.; Campagne, J.-M. J. Am. Chem. Soc.
2005, 127, 14180–14181. (b) Michaux, J.; Terrasson, V.; Marque, S.; Prim,
D.; Wehbe, J.; Campagne, J.-M. Eur. J. Org. Chem. 2007, 2601–2603.
(c) Terrasson, V.; Marque, S.; Prim, D.; Georgy, M.; Campagne, J.-M.
Adv. Synth. & Cat. 2006, 348, 2063–2067. (d) Dal Zotto, C.; Wehbe, J.;
Virieux, D.; Campagne, J.-M. Synlett 2008, 2033–2035. (e) Dal Zotto, C.;
Virieux, D.; Campagne, J.-M. Synlett 2009, 276–278. (f) Georgy, M.;
Debleds, O.; Dal Zotto, C.; Campagne, J.-M. Tetrahedron 2009, 65, 1758–
1766. (g) Terrasson, V.; Michaux, J.; Gaucher, A.; Wehbe, J.; Marque, S.;
Prim, D.; Campagne, J.-M. Eur. J. Org. Chem. 2007, 5332–5335. (h) Debleds,
O.; DalZotto, C.; Vrancken, E.; Campagne, J.-M.; Retailleau, P. Adv. Synth.
Catal. 2009, 351, 1991–1998.
In 1968, Baldwin and co-workers postulated that the weak-
ness of the nitrogen-oxygen bond would allow the thermal
rearrangement of isoxazoline into acylaziridine.1,2 A short
experimental study validated this initial hypothesis and high-
lighted the crucial role of the nature of the substituents on the
course of the reaction (Scheme 1). If the transformation has been
made object of mechanistical studies,2a,3 the potential of this
synthetic tool has been poorly exploited perhaps because of the
scarcity of described examples (three substrates) in the seminal
paper and because a further rearrangement of the acylaziri-
dine into oxazoline is sometimes observed. In 2002, Saito and
(6) Debleds, O.; Gayon, E.; Ostaszuk, E.; Vrancken, E; Campagne, J.-M.
Chem. Eur. J., in press.
(7) For reviews on reaction of aziridines, see: (a) Tanner, D. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 599–619. (b) Aziridines and Epoxides in Organic Synthesis;
Yudin, A. K., Ed.; Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2006.
(c)Padwa, A. inComprehensive Heterocyclic Chemistry, Vol III, Katritzky,A.R.,
Ed., Elsevier 2008, Vol 18, pp 1-97. (d) Sweeney, J. B. In Science of synthesis;
Shaumann, E., Enders, D., Eds; Thieme, Stuttgart, 2009; Vol 40a, Chapter
40.1.5. (e) Schneider, C. Angew. Chem., Int. Ed. Engl. 2009, 48, 2082–2084.
(f) Dauban, P.; Malik, G. Angew. Chem., Int. Ed. Engl. 2009, 48, 9026–9029.
(g) Lu, P. Tetrahedron 2010, 66, 2549–2560.
(8) Crystallographic data for the structural analysis of cis-3l have been
deposited with the Crystallographic Data Center, no. CCDC 777638. See the
Supporting Information for the ORTEP/X-ray structure.
(9) (a) Park, G.; Kim, S.-C.; Kang, H.-Y. Bull. Koran Chem. Soc. 2005, 26,
1339–1343. (b) Mimura, N.; Ibuka, T.; Akaji, M.; Miwa, Y.; Taga, T.; Nakai,
K.; Tamamura, H.; Fujii, N.; Yamamoto, Y. J. Chem. Soc. Chem. Commun.
1996, 3, 351–352. (c) Robiette, R. J. Org. Chem. 2006, 71, 2726–2734.
(1) Baldwin, J. E.; Pudussery, R. G.; Qureshi, A. K.; Sklarz, B. J. Am.
Chem. Soc. 1968, 90, 5325–5326.
(2) For reviews on 4-isoxazolines see: (a) Freeman, J. P. Chem. Rev. 1983,
83, 241–261. (b) Pinho e Melo, T. M. V. D. Eur. J. Org. Chem. 2010, 18, 3363–
3376.
ꢀ
ꢀ
(3) (a) Gree, R.; Carrie, R. J. Am. Chem. Soc. 1977, 90, 6667–6672.
(b) Chidichimo, G.; Cum, G.; Lelj, F.; Sindoma, G.; Uccella, N. J. Am.
Chem. Soc. 1980, 102, 1372–1377. (c) Lopez-Calle, E.; Eberbach, W. J. Chem.
Soc., Chem. Commun. 1994, 301–302. (d) Lopez-Calle, E.; Keller, M.;
Eberbach, W. Eur. J. Org. Chem. 2003, 1348–1453.
6050 J. Org. Chem. 2010, 75, 6050–6053
Published on Web 08/03/2010
DOI: 10.1021/jo101273d
r
2010 American Chemical Society

Gayon et al.
JOCNote
SCHEME 1. Baldwin Rearrangement of Isoxazoline
TABLE 2. Microwaves Rearrangement of 2a: Solvent Study
entrya
solvent
cis-3a/trans-3ab
convc (%)
transfd (%)
1
2
3
4
5
6
7
8
9
CH3CN
toluene
H2O
DMF
DMSO
DCE
EtOH
i-PrOH
neat
97/3
40
22
90
38
68
33
39
34
34
20
63
36
49
28
30
28
85/15
>97/3
94/6
>97/3
93/7
97/3
SCHEME 2. Dual Iron/Gold-Catalyzed One-Pot Synthesis of
Isoxazolines
88/12
degradation
aReaction conditions: 0.125M, 5 min reaction on a 0.125 mmol scale.
bDetermined by 1H NMR of the crude product. cDetermined by 1H
NMR of the crude product using 4-ethynylnitrobenzene as internal
standard. dProduct/(starting material þ product) percentage determined
by 1H NMR analysis of the crude product.
TABLE 3. Microwave-Assisted Rearrangement of 2a in CH3CN: Time
and Temperature Study
SCHEME 3. Rearrangement of 2a into cis-3a and trans-3a
entry time (min) T (°C) cis-3a/ trans-3aa convb (%) transfc (%)
1
2
3
4
5
6
7
8
5
5
5
5
5
10
15
30
90
100
110
120
130
110
110
110
93/7
95/5
97/3
>97/3
>97/3
>97/3
>97/3
>97/3
8
18
40
75
97
6 (nd)
14 (nd)
34 (nd)
61 (nd)
68 (nd)
60 (nd)
73 (nd)
100 (67)
TABLE 1. Thermal Rearrangement of 2a: Solvent Study
cis-3a/
trans-3aa
transf (%)b
(yield, %)c
aDetermined by 1H NMR of the crude product. bDetermined by 1H
NMR of the crude product using 4-ethynylnitrobenzene as internal
standard. cProduct/(starting material þ product) percentage determined
by 1H NMR of the crude product.
entry
solvent
toluene
T (°C)
time
2 h
1
2
110
83/17
92/8
100 (86)
100 (75)
100 (45)
50 (nd)
11 (nd)
50 (nd)
40 (nd)
80 (nd)
85 (52)
80 (nd)
100 (57)
4 h
3
4
5
6
7
8
9
10
11
16 h
8 h
45 min
1 h 30
3 h
6 h
8 h
2 h
4 h
>95/5
92/8
84/16
91/9
>95/5
>95/5
>95/5
95/5
dioxane
MeCN
100
85
time to avoid side reactions.11 Working with a microwave
synthesizer dedicated to chemistry, in a sealed-vessel config-
uration, also provided the possibility of heating the reaction
samples above the solvent boiling point in a safe manner.12
A study of the reaction conditions under microwave irradia-
tion was thus undertaken, and the results are summarized in
Table 2. We first examined the effect of solvent on the rearran-
gement of 2a in the following conditions: 0.125 M, 5 min reac-
tion, 110 °C, and on a 0.125 mmol scale (Table 2). As previously
observed in thermal reactions, apolar solvents give lower cis/
trans selectivities (see entries 2 and 6). Among the various polar
solvents tested, water and DMSO allow a good level of conver-
sion (90 and 68%, respectively) but, unfortunately, also induce
the formation of extensive amounts of degradation products
(63 and 43% transformation, respectively, see entries 3 and 5).
As compared to the other solvents used, CH3CN finally offers
the better compromise in term of efficiency (selectivity, conver-
sion, and transformation) and of practical convenience. Indeed,
at the end of the reaction, the solvent is removed in vacuo and
the residue is directly loaded on silica gel for purification, which
n-PrCN
125
>95/5
aDetermined by 1H NMR of the crude product. bProduct/(starting
material þ product) percentage determined by 1H NMR of the crude
product. cIsolated yield.
has a moderate influence on the conversion (compare entries
1 and 10) but has a significant effect on the dr. In more polar
solvent, higher selectivities are observed (compare entries 1,
6, and 10). High reaction temperatures are generally required
to obtain good conversions (entries 1, 4, 6, and 10), but
prolonged heating time result in a drastic drop of the yield
due to decomposition. These results are not that surprising in
light of previous reported examples where strong donating
nitrogen substituents appear to favor the rearrangement.1 In
our case, the presence of the sulfonyl group may explain the
hard reaction temperatures needed. In order to maintain
high yields and selectivities, the use of microwaves was thus
envisioned. Microwave activation in organic synthesis has
become an increasingly used technique for the preparation of
new molecules.10 Reactions are generally faster, cleaner, and
very often more selective. Furthermore, the focused heating
generated by the microwaves enables a high temperature to
be reached in a short time. Hence, this technique should be
particularly adapted to the rearrangement described herein
which necessitates elevated temperature and short reaction
(11) For selected examples of microwave-promoted rearrangement reactions
see:(a)Zuo, H.;Li, Z.-B.;Ren, F.-K.;Falck, J. R.;Meng, L.;Ahn, C.;Shin, D.-S.
Tetrahedron 2008, 64, 9669–9674. (b) Craig, D.; Paina, F.; Smith, S. C. Chem.
Commun. 2008, 3408–3410. (c) Gilday, J. P.; Lenden, P.; Moseley, J. D.; Cox,
B. G. J. Org. Chem. 2008, 73, 3130–313421. (d) Gonzalez, I.; Bellas, I.; Souto, A.;
Rodriguez, R.; Cruces, J. Tetrahedron Lett. 2008, 49, 2002–2004. (e) Pinto, D. C.
G. A.; Silva, A. M. S.; Cavaleiro, J. A. S. Synlett 2007, 12, 1897–1900. (f) Gonda,
J.; Martinkova, M.; Zadrosova, A.; Sotekova, M.; Raschmanova, J.; Conka, P.;
Gajdosikova, E.; Kappe, C. O. Tetrahedron Lett. 2007, 48, 6912–6915. (g) Du,
W.; Hu, Y. Synth. Commun. 2006, 36, 2035–2046. (h) Schobert, R.; Gordon,
G. J.; Mullen, G.; Stehle, R. Tetrahedron Lett. 2004, 45, 1121–1124. (i) Gillard,
A.-C.; Fabis, F.; Jolivet-Fouchet, S.; Rault, S. Tetrahedron Lett. 1997, 38, 2271–
2274.
(10) Microwaves in Organic Synthesis, 2nd ed.; Loupy, A., Ed.; Wiley-
VCH: Weinheim, 2006.
(12) For a review, see: Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43,
6250–6284.
J. Org. Chem. Vol. 75, No. 17, 2010 6051

Gayon et al.
SCHEME 5. Straightforward Access of Acylaziridines cis-
JOCNote
TABLE 4. Microwaves Rearrangement of Isoxazolines: Scope and
Limitations
3a-m from the Corresponding Propargylic Alcohols 1a-m
time pdt
T (°C) (min) (cis)
entry
R
R0
dra
yieldb (%)
alkyl and phenyl groups are used, the corresponding acyla-
ziridines cis-3d,j,k,m are obtained in 68-71% yields (entries 4,
10, 11, and 13). The lower yield obtained for the t-Bu-substi-
tuted cis-3l is explained by the competitive formation of corre-
sponding oxazoline 4l, isolated in 17% yield. It is interesting to
note that the presence of a bulky substituent on the alkene has
such a dramatic effect that the rate of the oxazoline formation
step becomes close to that of the acylaziridine step (Scheme 4).
Indeed, with an isopropyl substituent the oxazoline 4k is isolated
in 10% yield, whereas only a trace amount (<3%) of 4 could be
observed for nonbulky substituents, including the cyclopropyl
group.
1
2
3
4
5
6
7
8
9
10
11
12
13
p-tol
o-tol
m-tol
Ph
p-F-Ph
p-Ph-Ph
2-Napht
p-Br-Ph
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
110
110
110
130
130
120
120
130
110
130
130
130
130
30
30
30
15
15
20
20
20
20
15
20
30
30
3a
3b
3c
3d
3e
3f
3g
3h
3i
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
>97/3
67
80
87
70
74
66
63
64
35
68
71
59
71
p-MeOPh n-Bu
Ph
Ph
Ph
Ph
c-Pr
i-Pr
t-Bu
Ph
3j
3k
3l
3m >97/3
aDetermined by 1H NMR of the crude product. bIsolated yield.
In conclusion, this study expands the thermal rearrange-
ment of isoxazolines into acylaziridines initially reported by
Baldwin and demonstrates a possible clean and highly dias-
tereoselective rearrangement induced by microwave irradia-
tion. Combined with our recently developed dual gold-iron-
catalyzed synthesis of isoxazolines, this methodology allows
an efficient atom-economical access to N-benzenesulfona-
mide acylaziridines with high cis selectivity in two steps from
readily available propargylic alcohols (Scheme 5).13
SCHEME 4. Transformation of 2l into cis-3l and 4l
avoids an aqueous workup. The reaction conducted in the
absence of solvent resulted in the complete degradation of the
starting material.
Experimental Section
Typical Procedure A: Preparation of 5-Butyl-3-(naphthalen-2-
yl)-2-(phenylsulfonyl)-2,3-dihydroisoxazole (2g). To a solution of
1-(naphthalen-2-yl)hept-2-yn-1-ol (1g) (603 mg, 2.5 mmol, 1.2
equiv) in dichloromethane (5 mL) were added N-hydroxybenzene-
sulfonamide (365 mg, 1 mmol, 1 equiv) and FeCl3 (11mg,2.5mol%)
We thus next evaluated the influence of reaction conditions
(time and temperature) using CH3CN as solvent (Table 3).
The reaction is highly sensitive to temperature, as shown in
Table 3, entries1-5. For the rearrangement of 2a, the best
results are obtained when the reaction is carried out above
the solvent boiling point, at 110 °C (entry 3). At 90 °C, a slow
conversion is observed (entry 1), whereas from 120 to 130 °C,
product decomposition is detrimental to the transformation
(entries 4 and 5). In order to ensure complete conversion, a 30
min reaction time is required (entry 8). Under these opti-
mized conditions (CH3CN as solvent, 110 °C, 30 min), cis-3a
is isolated as a single diastereoisomer in 67% yield.
The possible influence of the nature of the aromatic and
the acetylenic substituents was next studied. In all cases,
compounds cis-3a-m have been obtained as a single diaster-
eoisomer, but careful optimization of temperature (110 to
130 °C) and reaction time (15 to 30 min) for each starting
material proved to be necessary to ensure good isolated
yields (see Table 4).
Studies on starting materials bearing a n-Bu in the acet-
ylenic position show that good yields are obtained whatever
the position (ortho, meta, para) and the nature (Me, Ph, F,
Br, naphthyl) of the substituents on the aromatic ring (see
entries 1-8), which allows further functional modifications.
A notable exception is the use of the methoxy group in the
para position, where a poor 35% yield is obtained due to the
competitive formation of unidentified side products.
The substituents on the olefinic moiety have little influence
on the reaction course, and when primary and secondary
at room temperature. The mixture was refluxed for 1 h, NaAuCl4
3
2H2O (52 mg, 5 mol %) and pyridine (41 μL, 0.1 mmol) were
added, and the reflux was maintained for an additional 2 h. After
reaction completion (TLC monitoring), the mixture was concen-
trated under vacuum and the crude material was purified by flash
chromatography on silica gel (cyclohexane/ethyl acetate 95/5) to
give the corresponding isoxazoline 2g (643 mg, 1.63 mmol, yield:
78%) as a pale yellow solid: mp 84-85 °C; 1H NMR (400 MHz,
CDCl3) δ (ppm) 0.88 (t, J = 7.6 Hz, 3H), 1.23-1.45 (m, 4H),
2.00-2.17 (m, 2H), 4.62 (m, 1H), 5.97 (m, 1H), 7.47-7.52 (m, 3H),
7.56-7.61 (m, 2H), 7.68-7.73 (m, 1H), 7.79-7.88 (m, 4H),
8.03-8.07 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 13.7,
22.2, 25.4, 28.4, 68,9, 95.9, 127.1 (2C), 127.4, 127.5 (2C), 127.6 (2C),
128.8 (2C), 129.0 (2C), 129.5 (2C), 134.1, 134.2, 138.9, 140.7, 141.4,
156.6; IR (KBr) ν (cm-1) 3057, 2957, 2871, 1687, 1601, 1509, 1447,
1361, 1171, 1088, 1020, 900, 860, 801, 751, 726, 688, 631, 579, 555,
477; MS (ESIþ) m/z 787 (30, [2M þ H]þ), 394 (100, [M þ H]þ), 301
(75), 255 (15), 221 (45); HRMS (ESIþ) m/z 394.1479, calcd for
C23H23NO3S þ Hþ 394.1477.
Typical Procedure B: Preparation of 1-(Phenylsulfonyl)-3-(p-
tolylaziridin-2-yl)pentan-1-one (cis-3a). Isoxazoline 2a (1.5 mmol,
535 mg) was dissolved in acetonitrile (12 mL) and was heated in a
sealed vessel at 110 °C during 30 min under microwave irradiation
(13) Attempts of a one pot sequential synthesis of the acyl-aziridine cis-3a
from the corresponding propargylic alcohol under microwave irradiation
and in CH3CN gave cis-3a in 35% isolated yield as compare to an overall
60% for the two step procedure.
6052 J. Org. Chem. Vol. 75, No. 17, 2010

Gayon et al.
JOCNote
(400 W, temperature-controlled mode). The resulting reaction
mixture was concentrated under vacuum and the crude material
directly purified by flash chromatography on silica gel (cyclo-
hexane/ether 9/1) to give the acylaziridine 3a (359.7 mg, 67%) as
a pale yellow oil: 1H NMR (400 MHz, CDCl3) δ (ppm) 0.66 (t, J =
7.2 Hz, 3H), 0.91-1.01 (m, 2H), 1.11-1.30 (m, 2H), 1.94 (ddd, J =
6.5, 8.1, 17.5 Hz, 1H), 2.13 (ddd, J = 6.3, 8.1, 17.5 Hz, 1H), 2.28 (s,
3H), 3.65 (d, J = 7.9 Hz, 1H), 4.14 (d, J = 7.9 Hz, 1H), 7.04-7.09
(m, 4H), 7.57-7.61 (m, 2H), 7.66-7.71 (m, 1H), 8.04-8.07 (m,
2H); 13C NMR (100 MHz, CDCl3) δ (ppm) 13.5, 21.1, 21.8, 24.6,
40.7, 45.8, 48.8, 127.2 (2C), 128.1 (2C), 128.2, 129.2 (2C), 129.3
(2C), 134.1, 137.1, 138.5, 202.6; IR (neat) ν(cm-1) 3066, 2957, 1712,
1448, 1330, 1164, 1090, 1023, 916, 818, 752, 688, 600, 564; MS
(ESIþ) m/z715 (15, [2M þ H]þ), 358 (100, [M þ H]þ),274(5),6(5);
MS (ESI-) m/z 356 (85, [M - H]-), 227 (100), 175 (30), 156 (20),
113 (50), 61 (5); HRMS (ESIþ) m/z 358.1480, calcd for
C20H23NO3S þ Hþ 358.1477.
(22), 255 (36); HRMS (ESIþ) m/z 344.1323, calcd for C19H21-
NO3S þ Hþ 344.1320. Crystal data for cis-3l: CCDC 777638, for-
mula=C19H21N1O3S1, T=175 K, Mr = 343.45 g mol-1, crystal
size=0.150 ꢀ 0.200 ꢀ 0.400 mm3, orthorhombic, space group Pbca,
˚
˚
˚
a=16.2244(6) A, b=11.0860(5) A, c=19.8492(8) A, R = 90°, β =
90°, γ = 90°, V = 3570.2(3) A , Z = 8, Fcalcd = 1.278 g cm-3, μ =
3
˚
0.197 mm-1, θmax = 29.189°, experimental resolution 0.77 A, 41166
˚
reflections measured, 4435 unique, 2339 with I > 2σ(I), Rint
=
0.091, <σ(I)/I>=0.041, refined parameters=217, R1(I > 2σ(I))=
0.0449, wR2(I > 2σ(I)) = 0.0782, R1(all data) = 0.1008, wR2
(all data) = 0.0782, GOF = 0.9584, ΔF(min/max) = -0.51/
-3
˚
0.28 e A
.
4l: 1H NMR (400 MHz, CDCl3) δ (ppm) 0.90 (s, 9H), 5.63 (s,
1H), 6.64 (s, 1H), 7.33-7.40 (m, 3H), 7.53-7.58 (m, 4H),
7.63-7.67 (m, 1H), 7.88-7.91 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ (ppm) 26.1 (3C), 30.0, 91.3, 99.3, 124.5 (2C), 127.2
(2C), 127.3 (2C), 127.7 (2C), 127.9, 132.4, 134.2, 137.0, 159.7; IR
(KBr) ν (cm-1) 2967, 1645, 1445, 1347, 1212, 1169, 1088, 1026,
986, 919, 890, 851, 742, 723, 688, 674, 630, 596, 573, 556; MS
(ESIþ) m/z 687 (10, [2M þ H]þ), 445 (15), 344 (100, [M þ H]þ),
202 (55), 167 (15), 102 (8); MS (ESI-) m/z 428 (20), 400 (15), 356
(15), 336 (10), 286 (80), 227 (55), 219 (40), 175 (30), 157 (50), 113
(100); HRMS (ESIþ) m/z 344.1324, calcd for C19H21NO3S þ
Hþ 344.1320.
2,2-Dimethyl-3-phenyl-1-((phenylsulfonyl)aziridin-2-yl)pro-
pan-1-one (cis-3l) and 4-tert-Butyl-2-phenyl-3-(phenylsulfonyl)-
2,3-dihydrooxazole (4l). According to typical procedure B (on
0.5 mmol scale, 130 °C, 30 min), 102.6 mg of compound 3l (0.299
mmol, 59% yield) as a white solid (mp 125-126 °C) and 29.0 mg
of compound 4l (0.084 mmol, 17% yield) as a white solid (mp
119 °C) were obtained. cis-3l and 4l were separated by flash
chromatography on silica gel (cyclohexane/ether 9/1, Rf (silica,
pentane/ether 8/2) = 0.33, UV/PMA).
Acknowledgment. We are grateful to the CNRS for finan-
ꢀ
cis-3l: 1H NMR (400 MHz, CDCl3) δ (ppm) 0.97 (s, 9H), 4.11
(d, J=7.7 Hz, 1H), 4.24 (d, J=7.7 Hz, 1H), 7.24-7.28 (m, 5H,),
cial support (ATIPE jeune equipe) and the Institut de Chimie
des Substances Naturelles (Gif sur Yvette) and the MESR
for Ph.D. grants (O.D., E,G., and J.-M.C.).
7.53-7.57 (m, 2H), 7.62-7.66 (m, 1H), 8.04-8.06 (m, 2H); 13
C
NMR (100 MHz, CDCl3) δ (ppm) 25.6, 43.7, 46.6, 47.0, 127.5
(2C), 127.8 (2C), 128.1 (2C), 128.5, 129.1 (2C), 131.1, 133.9, 137.6,
202.7; IR (KBr) ν (cm-1) 3066, 3033, 2969, 2933, 2871, 1716, 1478,
1448, 1367, 1329, 1170, 1091, 1072, 996, 912, 885, 802, 754, 731, 698,
688, 606, 577, 547; MS (ESIþ) m/z 344 (100, [M þ H]þ), 316 (28),
260(57);MS(ESI-) m/z342 (31, [M - H]-), 326(35),286(20), 283
Supporting Information Available: Spectral and analytical
and experimental procedures for compounds 2b,c,f,g, cis-3a-m,
and 4l, 4k; X-ray data for acylaziridine cis-3l. This material is
available free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 17, 2010 6053