Synthesis of substituted allylic sulfonamides from β-alkoxy aziridines and organolithium reagents

Article abstract of DOI:10.1055/s-2008-1032013

The scope and limitations of the organolithium-mediated conversion of β-methoxy N-tosyl aziridines derived from acyclic allylic alcohols into substituted allylic sulfonamides are described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032013

LETTER
237
Synthesis of Substituted Allylic Sulfonamides from b-Alkoxy Aziridines and
Organolithium Reagents
Synthesis of
S
t
ubstitut
e
e
d
A
llylic
S
ulfonamideshen P. Moore,a Peter O’Brien,*a Adrian C. Whitwood,a John Gildayb
a
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Fax +44(1904)432516; E-mail: paob1@york.ac.uk
b
Process R & D, AstraZeneca, Avlon Works, Severn Road, Hallen, Bristol BS10 7ZE, UK
Received 13 September 2007
O
OMe
( )n
Abstract: The scope and limitations of the organolithium-mediated
conversion of b-methoxy N-tosyl aziridines derived from acyclic al-
lylic alcohols into substituted allylic sulfonamides are described.
MeO
OMe
MeO
MeO
R
N
R
N
N
N
Ts
R
Ts
Key words: organolithium reagents, lithiation, stereoselective syn-
thesis, diastereoselectivity, sulfonamides
cis-6
4
5
trans-6
n = 1, 2
R = Ts, t-BuSO2 R = Ts, t-BuSO2
Me
MeO
The synthetic potential afforded by a-lithiated aziridines
generated from the deprotonation of N-sulfonyl aziridines
continues to expand1,2 and has been a topic of much inter-
est to our group over the last few years.3–6 In particular, we
have investigated the organolithium-mediated conversion
of b-methoxy N-tosyl aziridines 1 into substituted allylic
sulfonamides 3 (Scheme 1). These reactions are believed
to proceed via a-lithiated aziridines 2 which undergo car-
benoid insertion into a second equivalent of the organo-
lithium reagent (R4Li; probably via 1,2-metalate
rearrangement) and eventual elimination of lithium meth-
oxide. Our attention thus far has focused on N-tosyl aziri-
dines 4 (n = 1, 2) derived from cyclic alkenes (Figure 1),4
including the development of a new approach to azaspiro-
cycles.6 At the same time, Hodgson and co-workers have
reported a detailed study on the related reactions of dihy-
drofuran aziridines 5 (R = Ts and t-BuSO2) together with
a few examples of reactions with aziridines trans- and cis-
6 that are not fused to another ring (Figure 1).7
MeO
Me
N
MeO
Me
N
Ts
OMe
anti
N
Ts
Ts
7
8
9
OMe
syn
10 R = Me
11 R = n-Pr
12 R = i-Pr
R
Me
R
Me
N
N
Ts
Ts
Figure 1
Z-stereoselective allylic sulfonamide-forming process
and the generation of some unexpected products.
The synthesis of b-methoxy N-tosyl aziridines 7–9 and
syn- and anti-10–12 was carried out using our previously
developed approach to aziridines 4,4,6 namely aziridina-
tion of the corresponding allylic alcohols using Sharp-
less’s method8 (Chloramine-T, PhMe3NBr3, MeCN, r.t.,
6–16 h) and subsequent methylation. In this way, aziri-
dines 7–9 were readily prepared.9 The diastereoselective
synthesis of methoxy aziridines syn- and anti-10–12 was
accomplished either via aziridination of allylic alcohols
13–15 or reduction of keto aziridines 19–21 (Scheme 2).
Thus, Sharpless aziridination of allylic alcohols 13–15
was ~3:1 anti-selective and enabled good 43–62% isolat-
ed yields of hydroxy aziridines anti-16–18.10 Although
small amounts of syn-16–18 were isolated from these re-
actions, we found that oxidation of hydroxy aziridines
anti-16–18 to their corresponding ketones and subsequent
NaBH4-mediated reduction provided ca. 4:1 syn-selectiv-
ity, enabling hydroxy aziridines syn-16–18 to be isolated
in 64–79% yields. Thus, a stereoselective route to each
diastereomeric series was developed.
R2 R3
OMe R2
OMe R2
R4Li
R4Li
R1
NHTs
R1
R3
R1
R3
N
Ts
N
R4
Li
Ts
1
2
3
Scheme 1
Our intention was to further explore the scope and limita-
tions of the transformation of b-methoxy N-tosyl aziri-
dines 1 into allylic sulfonamides 3 (Scheme 1). For this,
we have studied the organolithium-mediated reactions of
different classes of N-tosyl aziridines (7–9, syn- and anti-
10–12) derived from a series of acyclic allylic alcohols.
Herein, we report our findings, including the preparation
of a number of synthetically useful allylic sulfonamides, a
The stereochemistry of hydroxy aziridine anti-16 was es-
tablished by X-ray crystallography of its corresponding p-
nitrobenzoate (Figure 2).11 The relative stereochemistry
of hydroxy aziridines 17 and 18 was assigned by analogy
since each of the aziridination reactions proceeded with
ca. 3:1 diastereoselectivity and each of the ketone reduc-
tions gave ~4:1 diastereoselectivity. In addition, the major
SYNLETT 2008, No. 2, pp 0237–0241
x
x.
x
x.
2
0
0
8
Advanced online publication: 04.01.2008
DOI: 10.1055/s-2008-1032013; Art ID: D28707ST
© Georg Thieme Verlag Stuttgart · New York

238
S. P. Moore et al.
LETTER
Chloramine-T
PhMe3NBr3
OH
OH
the sterically unhindered terminal aziridine position. This
side reaction can be suppressed by substitution at this car-
bon as in methoxy aziridine 8 which gave higher yields of
the allylic sulfonamides (38–61%) and TsNH2 was not
formed in these reactions. As noted in our previous work,
the best results were obtained using Me3SiCH2Li.
OH
+
R
Me
R
Me
R
Me
MeCN, r.t.,
16 h
N
Ts
N
Ts
anti/syn
70:30
75:25
70:30
56%
62%
43%
28%
22%
17%
16 R = Me
17 R = n-Pr
18 R = i-Pr
13 R = Me
14 R = n-Pr
15 R = i-Pr
Dess–Martin
periodinane
RLi (2.5 equiv), Et2O
NaBH4
MeOH
O
OH
R
MeO
NHTs
+
TsNH2
N
Ts
–78 °C, 5 min
then to r.t. over 1 h
anti-16–18
R
R
Me
Me
0 °C, 3 h
CH2Cl2, r.t.
2 h
7
N
Ts
N
22 R = n-Bu
23 R = s-Bu
Ts
64% (9%)
40%
–*
14%
24%
32%
52%
syn/anti
85:15
75:25
80:20
syn-16
syn-17 74% (25%)
79% (19%)
19 83%
20 94%
21 98%
16 R = Me
17 R = n-Pr
18 R = i-Pr
24 R = CH2SiMe3
* TsNH2 observed in 1H NMR
spectrum of crude product
syn-18
Scheme 2
NHTs
RLi (2.5 equiv), Et2O
MeO
Me
Me
N
Ts
–78 °C, 5 min
then to r.t. over 1 h
(syn) diastereomer from the keto aziridine reductions was
8
R
the first to elute from the chromatographic separation and
25 R = n-Bu
26 R = s-Bu
27 R = CH2SiMe3
38%
56%
61%
1
3
in the H NMR spectra, the J values between the CHO
and adjacent CHN protons were larger for syn-16–18 (6–
8 Hz) than for anti-16–18 (4–5 Hz). These assignments
are consistent with a Felkin–Anh model for reduction of
the keto aziridines, as has been observed in related N-alkyl
aziridines.12 Subsequent Ag2O- or KHMDS-mediated meth-
ylation gave methoxy aziridines syn- and anti-10–12.13
Scheme 3
Next, reactions of methoxy aziridine 9 using the same
three organolithium reagents were investigated. Under the
standard conditions in Et2O, allylic sulfonamides 28–30
were generated in low yields (26–37%). However, in
these cases, a significant proportion of the mass balance
could be accounted for by the formation of enesulfona-
mide 31 (25–38%).15 Presumably, to form 31, a-lithiation
of the aziridine occurs and this is followed by an elimina-
tion process (unlikely to be concerted) in which the two
methyl groups are able to stabilize a developing positive
charge as the C–N bond breaks. We only ever observe the
formation of enesulfonamides like 31 when the aziridine
is equipped with three substituents.4 The formation of al-
lylic sulfonamides 28–30 from methoxy aziridine 9 con-
trasts with the reaction of a structurally related methoxy
epoxide which gave an allylic alcohol via b-elimination
on one of the methyl groups (and not via the a-lithiation
pathway).16
Figure 2
MeO Me
Me
NHTs
R–Li (2.5 equiv), Et2O
Me
MeO
Me
+
Me
Me
–78 °C, 5 min
then to r.t. over 1 h
To start with, the reactions of methoxy aziridines 7 and 8
with three different, commercially available organolithi-
um reagents (n-BuLi, s-BuLi, and Me3SiCH2Li) were
evaluated. We used the conditions that had been success-
ful for reactions of methoxy aziridines 4,4,6 namely 2.5
equivalents RLi at –78 °C in Et2O for five minutes before
warming to room temperature over one hour and then
quenching (Scheme 3). Encouragingly, allylic sulfona-
mides 22–27 were generated from the methoxy aziridines,
albeit in variable yields (24–61%).14 The yields of allylic
sulfonamides were lower with the simplest methoxy azir-
idine 7 (24–52%) and some of the mass balance was ac-
counted for by the formation of TsNH2. TsNH2 is
presumably generated by reductive alkylation3b of an or-
ganolithium intermediate where lithiation has occurred on
N
NHTs
R
Ts
9
31
38%
25%
32%
28 R = n-Bu
29 R = s-Bu
26%
34%
37%
30 R = CH2SiMe3
Me
s-BuLi, THF
ligand
NHTs
NHTs
+
Me
MeO
Me
MeO
Me
Me
–78 °C, 5 min
then to r.t.
over 1 h
N
Me
Ts
9
32
33
2.5 equiv s-BuLi, no ligand
3.0 equiv s-BuLi, TMEDA
3.0 equiv s-BuLi, PMDETA
43%
32%
52%
14%
17%
8%
Scheme 4
Synlett 2008, No. 2, 237–241 © Thieme Stuttgart · New York

LETTER
Synthesis of Substituted Allylic Sulfonamides
239
In an attempt to improve the yields of the allylic sulfona- Table 1 Organolithium-Mediated Transformations of Methoxy
Aziridines syn-10–12 to Allylic Sulfonamides (Z)-34–42 (Scheme 5)
mides, we briefly explored variation of solvent and the ef-
fect of additives. To our surprise, using s-BuLi in THF in
Entry SM
R1
R2
Product Yield (%)a
the presence of ligands (TMEDA or pentamethyldiethyl-
enetriamine, PMDETA), methoxy aziridine 9 was con-
verted into alkynyl sulfonamide 32 as the major product
(32–52%, Scheme 4).17 A similar alkyne-forming reaction
starting from dihydrofuran aziridines 5 has previously
been reported by our group5 and use of the optimized con-
ditions (3.0 equiv s-BuLi, PMDETA in THF) gave a sat-
isfactory 52% yield of alkyne 32. The formation of alkyne
32 can be imagined as proceeding via a lithiated aziridine
followed by a second lithiation and two elimination
events, although we have been unable to determine the or-
der of these steps. Enol ether 33 (E-stereochemistry estab-
1
2
3
4
5
6
7
8
9
syn-10
Me
n-Bu
34
35
36
37
38
39
40
41
42
29
34
59
18
39
54
12
25
39
syn-10
syn-10
syn-11
syn-11
syn-11
syn-12
syn-12
syn-12
Me
s-Bu
Me
Me3SiCH2
n-Bu
n-Pr
n-Pr
n-Pr
i-Pr
i-Pr
i-Pr
s-Bu
Me3SiCH2
n-Bu
3
s-Bu
lished from J = 13.0 Hz across the alkene) was also
isolated from these reactions in 8–17% yield.18 However,
resubjecting enol ether 33 to the standard reaction condi-
tions did not give alkyne 32, thus precluding lithiated 33
as being an intermediate en route to the alkyne.
Me3SiCH2
a Isolated yield after chromatography.
which insert into a second organolithium reagent (proba-
bly via a 1,2-metalate rearrangement) to give 44. Subse-
quent anti-elimination of lithium methoxide from
intermediates 44 would then generate the Z-configured al-
lylic sulfonamides 34–42.
Finally, we also explored the organolithium-mediated re-
actions of the diastereomeric methoxy aziridines syn- and
anti-10–12. Disappointingly, none of the expected allylic
sulfonamides were generated from the reactions of meth-
oxy aziridines anti-10–12 with Me3SiCH2Li; the only
identifiable product in each case was recovered starting
methoxy aziridines (23–90% recovery). In contrast, the
reactions of methoxy aziridines syn-10–12 were far more
successful giving Z-allylic sulfonamides 34–42 in 12–
59% yield (Scheme 5 and Table 1). Allylic sulfonamides
34–42 were generated as single diastereomers and their Z-
stereochemistry was established using 1D NOEs in the
their 1H NMR spectra. As noted throughout our studies in
this area, the highest yields (39–54%) were obtained using
Me3SiCH2Li.
To summarize, we report here the preparation of several
allylic sulfonamides (22–27, 28–30 and (Z)-34–42) via
the organolithium-mediated reactions of a range of meth-
oxy aziridines. Although the yields are variable, our ap-
proach represents a simple and direct route to substituted
allylic sulfonamides and is complementary to other ap-
proaches.20 Finally, the identification of different alterna-
tive reaction pathways have enabled us to map out the
scope and limitations of these reactions.
Acknowledgment
R1
NHTs
Me
OMe
R2Li (2.5 equiv), Et2O
We thank the EPSRC and AstraZeneca for an Industrial CASE
award (to S.P.M.).
R1
Me
H
–78 °C, 5 min
then to r.t. over 1 h
N
Ts
R2
syn-10–12
R
(Z)-34–42
References and Notes
1 = Me, n-Pr, i-Pr
anti-
(1) (a) Hodgson, D. M.; Humphreys, P. G.; Hughes, S. R. Pure
Appl. Chem. 2007, 79, 269. (b) Hodgson, D. M.; Bray, C.
D.; Humphreys, P. G. Synlett 2006, 1. (c) For a special
issue of Tetrahedron on oxiranyl and aziridinyl anions, see:
Tetrahedron 2003, 59, 9693. (d) Satoh, T. Chem. Rev. 1996,
96, 3303. (e) Doris, E.; Dechoux, L.; Mioskowski, C. Synlett
1998, 337. (f) Hodgson, D. M.; Gras, E. Synthesis 2002,
1625.
R2Li
elimination
R1
NTs
Li
OMe
MeO NTs
Li
OMe
H
R2Li
R1
Me
N
Ts
R1
Me
Me
R2 Li
Li
R2
44
Li
43
44
(2) For recent examples, see: (a) Hodgson, D. M.; Humphreys,
P. G.; Xu, Z.; Ward, J. G. Angew. Chem. Int. Ed. 2007, 46,
2245. (b) Hodgson, D. M.; Humphreys, P. G.; Ward, J. G.
Org. Lett. 2006, 8, 995. (c) Hodgson, D. M.; Miles, S. M.
Angew. Chem. Int. Ed. 2006, 45, 935. (d) Concellón, J. M.;
Suárez, J. R.; del Solar, V. Org. Lett. 2006, 8, 349.
(e) Hodgson, D. M.; Humphreys, P. G.; Ward, J. G. Org.
Lett. 2005, 7, 1153.
Scheme 5
By analogy with a related reaction on a dihydrofuran ep-
oxide,19 we suggest that the formation of Z-allylic sul-
fonamides 34–42 can be accounted for by the mechanism
shown in Scheme 5. Thus, a-lithiation of methoxy aziri-
dines syn-10–12 occurs to give lithiated aziridines 43
(3) (a) O’Brien, P.; Rosser, C. M.; Caine, D. Tetrahedron Lett.
2003, 44, 6613. (b) O’Brien, P.; Rosser, C. M.; Caine, D.
Tetrahedron 2003, 59, 9779.
Synlett 2008, No. 2, 237–241 © Thieme Stuttgart · New York

240
S. P. Moore et al.
LETTER
(13) Ag2O-Mediated-Methylation Conditions: Ag2O, MeI,
(4) Rosser, C. M.; Coote, S. C.; Kirby, J. P.; O’Brien, P.; Caine,
D. Org. Lett. 2004, 6, 4817.
(5) Huang, J.; O’Brien, P. Chem. Commun. 2005, 5696.
(6) Moore, S. P.; Coote, S. C.; O’Brien, P.; Gilday, J. Org. Lett.
2006, 8, 5145.
Et2O, r.t., 48 h. Yields: anti-10, 85%; syn-10, 60%; anti-11,
60%; syn-11, 64%; anti-12, 14% + 31% starting material +
8% N-Me epoxide from aza-Payne rearrangement; syn-12,
20% + 50% starting material.
(7) (a) Hodgson, D. M.; Stefane, B.; Miles, T. J.; Witherington,
J. Chem. Commun. 2004, 2234. (b) Hodgson, D. M.;
Stefane, B.; Miles, T. J.; Witherington, J. J. Org. Chem.
2006, 71, 8510.
(8) Jeong, J. U.; Tao, B.; Sagasser, I.; Henniges, H.; Sharpless,
K. B. J. Am. Chem. Soc. 1998, 120, 6844.
KHMDS-Mediated-Methylation Conditions: KHMDS,
MeI, THF, –78 °C (1 h) to r.t. (20 h). Yield: syn-12, 74%;
anti-12, 0% + 94% N-Me epoxide from aza-Payne
rearrangement.
(14) 4-Methyl-N-(1-methyl-2-trimethylsilanylmethyl-prop-2-
enyl)benzenesulfonamide (27)
(9) Aziridination Conditions: Chloramine-T (1.1 equiv),
PhMe3NBr3 (0.1 equiv), MeCN, r.t., 6 or 16 h (6 h for allyl
alcohol; 16 h for trans-crotyl alcohol and prenyl alcohol).
Methylation Conditions: Ag2O, MeI, Et2O, r.t., 48 h. Using
these conditions, allyl alcohol gave the aziridine (24%) and
then methyl ether 7 (77%); trans-crotyl alcohol gave the
aziridine (90%) and then methyl ether 8 (78%), and prenyl
alcohol gave the aziridine (78%) and then methyl ether 7
(66%).
Trimethylsilylmethyllithium (1.31 mL of a 0.72 M solution
in pentane, 0.94 mmol) was added dropwise to a stirred
solution of aziridine 8 (96 mg, 0.38 mmol) in Et2O (5 mL) at
–78 °C under Ar. After stirring at –78 °C for 5 min, the
resulting pale yellow solution was allowed to warm to r.t.
over 1 h. Sat. NH4Cl(aq) (5 mL) was then added and the layers
were separated. The aqueous layer was extracted with Et2O
(3 × 5 mL) and the combined organics were dried (MgSO4)
and evaporated under reduced pressure to give the crude
product. Purification by flash column chromatography on
silica with PE–Et2O (2:1) as eluent gave allylic sulfonamide
27 (71 mg, 61%) as a colorless oil; Rf = 0.2 (PE–Et2O, 2:1).
IR (CHCl3): 3386 (NH), 2957, 1637, 1599, 1414, 1333
(SO2), 1159 (SO2), 1090 cm–1. 1H NMR (400 MHz, C6D6):
d = 7.90 (d, J = 8.0 Hz, 2 H, 2-C6H4SO2), 6.83 (d, J = 8.0 Hz,
2 H, 3-C6H4SO2), 5.34 (d, J = 7.0 Hz, 1 H, NH), 4.84 (s, 1 H,
=CHAHB), 4.56 (s, 1 H, =CHAHB), 3.76 (quin, J = 7.0 Hz, 1
H, CHN), 1.92 (s, 3H, ArMe), 1.43 (d, J = 14.0 Hz, 1 H,
CHAHBSi), 1.28 (d, J = 14.0 Hz, 1 H, CHAHBSi), 1.06 (d,
J = 7.0 Hz, 3 H, Me), –0.05 (s, 9 H, SiMe3). 13C NMR (100.6
MHz, C6D6): d = 147.7 (=C), 142.7 (ipso-C6H4SO2), 139.3
(ipso-C6H4Me), 129.6 (2-C6H4SO2), 127.7 (3-C6H4SO2),
108.6 (=CH2), 54.5 (CHN), 23.4 (CH2Si), 21.4 (ArMe), 20.5
(Me), –1.38 (SiMe3). MS (CI, NH3): m/z (%) = 312 (66) [M
+ H]+, 244 (100), 174 (81), 73 (44). HRMS (CI, NH3): m/z
calcd for C15H25NO2SSi [M + H]+: 312.1454; found:
312.1452.
(10) 1-[3-Methyl-1-(toluene-4-sulfonyl)-aziridin-2-yl]butan-
1-ol (syn-17 and anti-17)
Phenyltrimethylammonium tribromide (264 mg, 0.70 mmol)
was added to a stirred suspension of Chloramine-T
trihydrate (2.17 g, 7.71 mmol) and 2-hepten-4-ol (0.95 mL,
7.01 mmol) in MeCN (35 mL) at r.t. under N2. After stirring
the pale yellow suspension at r.t. for 20 h, the solids were
removed by filtration through a plug of silica and washed
with EtOAc (150 mL). The resulting filtrate was evaporated
under reduced pressure to give the crude product, which
contained a 75:25 mixture of anti- and syn-17 (by 1H NMR
spectroscopy). Purification by flash column chromatography
on silica with PE–EtOAc (5:2) as eluent gave syn-17 (436
mg, 22%) and anti-17 (1.24 g, 62%), both as pale yellow
oils.
Compound syn-17: Rf = 0.3 (PE–EtOAc, 5:2). IR (CHCl3):
3537 (OH), 2964, 1598, 1320 (SO2), 1158 (SO2) cm–1. 1H
NMR (400 MHz, CDCl3): d = 7.85 (d, J = 8.5 Hz, 2 H, 2-
C6H4SO2), 7.33 (d, J = 8.5 Hz, 2 H, 3-C6H4SO2), 3.68–3.62
(m, 1 H, CHO), 2.92 (qd, J = 6.0, 4.5 Hz, 1 H, CHN), 2.77
(dd, J = 6.5, 4.5 Hz, 1 H, CHN), 2.44 (s, 3 H, ArMe), 2.30 (d,
J = 4.5 Hz, 1 H, OH), 1.48 (d, J = 6.0 Hz, 3 H, Me), 1.46–
1.32 (m, 4 H), 0.90 (t, J = 7.0 Hz, 3 H, Me). 13C NMR (100.6
MHz, CDCl3): d = 144.2 (ipso-C6H4SO2), 137.4 (ipso-
C6H4Me), 129.7 (2-C6H4SO2), 127.3 (3-C6H4SO2), 70.0
(CHO), 54.5 (CHN), 43.2 (CHN), 37.2 (CH2), 21.6 (ArMe),
18.6 (CH2), 14.7 (Me), 13.9 (Me). MS (CI, NH3): m/z (%) =
284 (100) [M + H]+. HRMS (CI, NH3): m/z calcd for
C14H21NO3S [M + H]+: 284.1318; found: 284.1320.
Compound anti-17: Rf = 0.2 (PE–EtOAc, 5:2). IR (CHCl3):
3567 (OH), 2963, 1599, 1456, 1321 (SO2), 1159 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.83 (d, J = 8.0 Hz, 2 H, 2-
C6H4SO2), 7.32 (d, J = 8.0 Hz, 2 H, 3-C6H4SO2), 3.68 (br s,
1 H, CHO), 2.94 (qd, J = 6.0, 4.0 Hz, 1 H, CHN), 2.88 (t,
J = 4.0 Hz, 1 H, CHN), 2.44 (s, 3 H, ArMe), 1.92 (d, J = 3.0
Hz, 1 H, OH), 1.64 (d, J = 6.0 Hz, 3 H, Me), 1.44–1.32 (m,
4 H), 0.87 (t, J = 7.0 Hz, 3 H, Me). 13C NMR (100.6 MHz,
CDCl3): d = 144.2 (ipso-C6H4SO2), 137.6 (ipso-C6H4Me),
129.6 (2-C6H4SO2), 127.3 (3-C6H4SO2), 68.0 (CHO), 51.5
(CHN), 42.5 (CHN), 36.3 (CH2), 21.5 (ArMe), 18.2 (CH2),
14.1 (Me), 13.7 (Me). MS (CI, NH3): m/z (%) = 284 (100)
[M + H]+. HRMS (CI, NH3): m/z calcd for C14H21NO3S
[M + H]+: 284.1318; found: 284.1320.
(15) Characterization Data for 31
White solid, mp 45–46 °C. Rf = 0.2 (PE–Et2O, 3:2). IR
(CHCl3): 3327 (NH), 2927, 1450, 1324 (SO2), 1162 (SO2),
1091 cm–1. 1H NMR (400 MHz, CDCl3): d = 7.73 (d, J = 8.0
Hz, 2 H, 2-C6H4SO2), 7.28 (d, J = 8.0 Hz, 2 H, 3-C6H4SO2),
5.93 (s, 1 H, NH), 3.60 (s, 2 H, CH2O), 3.11 (s, 3 H, OMe),
2.42 (s, 3 H, ArMe), 1.71 (s, 6 H, 2 × Me). 13C NMR (100.6
MHz, CDCl3): d = 143.4 (ipso-C6H4SO2), 137.9 (ipso-
C6H4Me), 136.7 (=C), 129.5 (2-C6H4SO2), 127.3 (3-
C6H4Me), 123.6 (=CNH), 69.1 (CH2O), 57.8 (OMe), 21.5
(ArMe), 20.6 (Me), 19.7 (Me). MS (CI, NH3): m/z (%) = 270
(45) [M + H]+, 238 (100). HRMS (CI, NH3): m/z calcd for
C13H19NO3S [M + H]+: 270.1164; found: 270.1161.
(16) Doris, E.; Dechoux, L.; Mioskowski, C. Chem. Commun.
1996, 549.
(17) Characterization Data for 32
White solid, mp 91–92 °C. Rf = 0.2 (PE–Et2O, 3:2). IR
(CHCl3): 3306 (NH), 3019, 1382, 1328 (SO2), 1149 (SO2),
1093 cm–1. 1H NMR (400 MHz, CDCl3): d = 7.81 (d, J = 8.0
Hz, 2 H, 2-C6H4SO2), 7.28 (d, J = 8.0 Hz, 2 H, 3-C6H4SO2),
5.25 (NH), 2.42 (s, 3 H, ArMe), 2.09 (s, 1 H, CH), 1.54 (s, 6
H, 2 × Me). 13C NMR (100.6 MHz, CDCl3): d = 143.1 (ipso-
C6H4SO2), 138.8 (ipso-C6H4Me), 129.2 (2-C6H4SO2), 127.6
(3-C6H4SO2), 85.3 (CH), 71.2 (C), 49.8 (CN), 30.6 (2 × Me),
21.5 (ArMe). MS (CI, NH3): m/z (%) = 255 (100) [M +
NH4]+, 238 (46), 189 (60). HRMS (CI, NH3): m/z calcd for
C12H15NO2S [M + H]+: 255.1167; found: 255.1160.
(18) Characterization Data for 33
(11) CCDC reference number 658331.
(12) (a) Bartnik, R.; Lesniak, S.; Laurent, A. Tetrahedron Lett.
1981, 22, 4811. (b) Yun, J. M.; Sim, T. B.; Hahm, H. S.;
Lee, W. K. J. Org. Chem. 2003, 68, 7675.
White solid, mp 74–75 °C. Rf = 0.1 (PE–Et2O, 3:2). IR
Synlett 2008, No. 2, 237–241 © Thieme Stuttgart · New York

LETTER
(CHCl3): 3306 (NH), 3019, 1571, 1327 (SO2), 1163 (SO2),
Synthesis of Substituted Allylic Sulfonamides
241
108.6 (=CH), 58.0 (CN), 55.4 (OMe), 29.2 (2 × Me), 21.5
(ArMe). MS (CI, NH3): m/z (%) = 270 (5) [M + H]+, 238
(82), 99 (100). HRMS (CI, NH3): m/z calcd for C13H19NO3S
[M + H]+: 270.1164; found: 270.1158..
1092 cm–1. 1H NMR (400 MHz, CDCl3): d = 7.74 (d, J = 8.0
Hz, 2 H, 2-C6H4SO2), 7.27 (d, J = 8.0 Hz, 2 H, 3-C6H4SO2),
6.36 (d, J = 13.0 Hz, 1 H, =CHO), 4.73 (s, 1 H, NH), 4.57 (d,
J = 13.0 Hz, 1 H, =CH), 3.26 (s, 3 H, OMe), 2.42 (s, 3 H,
ArMe), 1.35 (s, 6 H, 2 × Me). 13C NMR (100.6 MHz,
CDCl3): d = 147.7 (=CH), 142.8 (ipso-C6H4SO2), 140.2
(ipso-C6H4Me), 129.3 (2-C6H4SO2), 127.2 (3-C6H4SO2),
(19) Hodgson, D. M.; Stent, M. A. H.; Wilson, F. X. Org. Lett.
2001, 3, 3401.
(20) Barchuk, A.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc.
2007, 129, 8432.
Synlett 2008, No. 2, 237–241 © Thieme Stuttgart · New York

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