Four component synthesis of (Z)-4-alkoxy-1,3-dimethylalk-2-enyl methyl sulfones: On the intermediacy of sultines (3,6-dihydro-1,2-oxathiin-2-oxides) arising from suprafacial hetero-Diels-Alder additions of sulfur dioxide

Article abstract of DOI:10.1016/S0040-4039(00)02102-X

The reactions of (E,E)-1-benzyloxy-2-methylpenta-1,3-diene (9) with 3,3-dimethyl-2-(trimethylsilyloxy)butene and (Z)-3-(trimethylsilyloxy)pent-2-ene in SO₂ and a Lewis acid give silyl sulfinates that are quenched with MeI to generate the corres

Full text of DOI:10.1016/S0040-4039(00)02102-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 673–675
Four component synthesis of (Z)-4-alkoxy-1,3-dimethylalk-2-enyl
methyl sulfones: on the intermediacy of sultines
(3,6-dihydro-1,2-oxathiin-2-oxides) arising from suprafacial
hetero-Diels–Alder additions of sulfur dioxide
Sophie Megevand,a Jonathan Moore,a Kurt Schenkb and Pierre Vogela,*
aSection de Chimie de l’Universite´ de Lausanne, BCH, CH-1015 Lausanne-Dorigny, Switzerland
bInstitut de Cristallographie, BSP, Universite´ de Lausanne, CH-1015 Lausanne-Dorigny, Switzerland
Received 28 June 2000; accepted 14 November 2000
Abstract—The reactions of (E,E)-1-benzyloxy-2-methylpenta-1,3-diene (9) with 3,3-dimethyl-2-(trimethylsilyloxy)butene and
(Z)-3-(trimethylsilyloxy)pent-2-ene in SO2 and a Lewis acid give silyl sulfinates that are quenched with MeI to generate the
corresponding (Z)-4-benzyloxy-1,3-dimethylalk-2-enyl methyl sulfones with unlike relative configuration at C-1 and C-4 (by X-ray
diffraction studies), in support of processes involving the intermediacy of a sultine arising from the suprafacial hetero-Diels–Alder
addition of SO2 to diene 9. © 2001 Elsevier Science Ltd. All rights reserved.
When enoxysilanes 1 and (E,E)-2-methyl-1-silyloxy-
penta-1,3-diene 2 are mixed in SO2/CH2Cl2 at −78°C
containing a Lewis acid (Yb(OTf)3, (t-Bu)Me2SiOTf), a
carbonꢀcarbon bond is formed between the electron-
rich alkene and the electron-rich diene with formation
of the corresponding unstable sulfinates 3 (Scheme 1).
Treatment of 3 with Bu4NF liberates the corresponding
sulfinic acids 4 that can be quenched with MeI to
generate the corresponding methyl sulfones 5, or be
allowed to undergo retro-ene eliminations of SO2 with
the exclusive formation of (anti,E)-3-hydroxy-4-methyl-
1-phenylhept-5-en-1-one (6a) and (anti,E)-4-hydroxy-5-
methyloct-6-en-2-one (6b).1 The structures of 6a,b were
established unambiguously, but not those of 5a,b. We
have now carried out further studies with (E,E)-1-ben-
zyloxy-2-methylpenta-1,3-diene (9), SO2 and the two
enoxysilanes 10 (3,3-dimethyl-2-trimethylsilyloxy)bu-
tene) and 26 ((Z)-3-(trimethylsilyloxy)pent-2-ene).
Crystalline sulfones have been isolated and their struc-
tures have been established unambiguously by X-ray
diffraction studies.2 The results shed light on the mech-
anism of reactions shown in Scheme 1.
Boiling of 7 with benzyl alcohol in toluene under acidic
conditions3 generated 8 (77%) that was reduced with
LiAlH4 to furnish an allylic alcohol that was esterified
Me
OR'
Me
OR'
SO2Me
H
SO2R''
O
O
OSiMe3
Me
SO2, CH2Cl2
Lewis acid, -78oC
MeI
R'O
+
R
R
R
Me
Me
Me
3 R'' = SiMe3
-SO2
20oC
5
1
a) R = Ph
b) R = Me
2 R' = (t-Bu)Me2Si
Bu4NF
O
OR' H
4 R'' = H
γ
Me
H
β
R
Me
6 (β,γ-anti)
Scheme 1.
Keywords: aldols; alkenylation; cycloaddition; sulfinic acids; X-ray crystallography.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02102-X

674
S. Mege6and et al. / Tetrahedron Letters 42 (2001) 673–675
with p-nitrobenzoyl chloride (Scheme 2). The corre-
sponding ester eliminated 1 equivalent of p-nitroben-
zoic acid at 20°C in the presence of Et3N, providing
diene 9 (60%). When a 1:1 mixture of 9 and enoxysilane
10 was added to a stirred solution of 0.2 equivalents of
(t-Bu)Me2SiOSO2CF3 in 2:1 CH2Cl2/SO2, an unstable
silyl sulfinate (22, see Scheme 3) was formed that was
reacted with Bu4NF in THF, then with an excess of
MeI to produce methyl sulfone 11 as single product
(77%).4 X-ray diffraction of a monocrystal of 11 estab-
lished its structure ((Z)-alkene, unlike configuration
at C-1 and C-4).2 In the absence of MeI retro-ene
elimination of SO2 occurred with formation of b-benzyl-
oxyketone 12 (30% yield).5 Its structure was proven by
its reduction with NaBH4, which produced a 1:2 mix-
ture of alcohols 13 and 14 that were separated by flash
chromatography on silica gel. Ozonolysis of 14 gave a
1
2:1 mixture of a- and b-pyranose 15, the H and 13C
NMR spectra of which proved (3J(H,H), NOESY) their
relative configurations.
Contrary to (E)-1-acetoxybutadiene that adds SO2 in
the presence of CF3COOH at −75°C giving 6-acetoxy-
3,6-dihydro-1,2-oxathiin-2-oxides,6 in the absence of
enoxysilane 10, SO2 added to diene 9 (−10 to −50°C)
producing the sulfolene 16. No trace of the expected
O
OSiMe3
1. LiAlH4/THF, -78 - 25oC, 15 h
2. p-NO2C6H4COCl, Et3N, DMAP (cat.)
-10 - 20oC, 50 h, 60%
BnO
+
OR'
BnOH/toluene/APTS
115oC, 3 h, 77%
7 R' = H
8 R' = Bn
9
10
0.2 eq (t-Bu)Me2SiOSO2CF3, CH2Cl2/SO2, 9+10 (1:1)
-75oC, 5 h, evaporation SO2/CH2Cl2
Bu4NF, THF, MeI, 20oC, 15 h, 77%
Me
OBn
SO2Me
O
OBn
O
1
2
9
1 eq Yb(OSO2CF3)3, CH2Cl2/SO2,
Bu4NF (5:2) 9+10 (1:1), -78oC, 24 h,
NH4Cl, MeOH/H2O (1:1), 16 h, 30%
6
5
3
4
9 + 10
4
8
12
11
OBn
Y
X
O
OH
NaBH4, MeOH, 0oC
1. O3 (3% in O2), CH2Cl2,
-78oC
12
14
chromatography
2. Me2S, 20oC, 15 h, 22%
OBn
13 X = OH, Y = H
14 X = H, Y = OH
15 (α/β 2:1)
Scheme 2.
OBn
H
OBn
Me
Me
Me
SO2
Me
BnO
H
Me SO2LA
Me SO2LA
16
11
17
11
18
11
+ 10
+ 10
OBn
O
R
+ 10
H
Me
Me
Me
H
H
Me
H
Me
H
H
Me
H
BnO
BnO
Me
S OLA
H
OBn
SO2LA
SO2LA
O
SO2R''
?
21
22 R'' = Me3Si
25 R'' = H
19
11
20
11
MeI
11
12
H
H
H
O
H
+ 10
Me
Me
Me
OBn
Me
Me
OBn
H
H
11
S
OBn
O
S
S OLA
O
O
O
?
24
21
11
12
24'
23
23
Scheme 3.

S. Mege6and et al. / Tetrahedron Letters 42 (2001) 673–675
675
SO2Me
SO2Me
OSiMe3
O
OBn
O
OBn
1
+SO2
+ MeI
+
4
9 +
26
27
28
Scheme 4.
sultine was observed. Sulfolene 16 did not react with 10
in the presence of SO2 and (t-Bu)Me2SiOTf or Yb(OTf)3,
but underwent polymerization above −40°C. Similar
observations were made with (E)-1-methoxybutadiene.7
Thus, 16 is not an intermediate of the oxyallylation
process. Because of the exclusive formation of 11 with
a (Z) olefinic moiety, zwitterionic intermediates 17 and
18, resulting from a hypothetical direct addition of SO2
onto the s-trans conformer of 9, cannot be intermediates
of the reactions 9+10+SO2“22“11. Direct additions of
SO2 to the s-cis-conformer of diene 9 could lead to
zwitterions 19, 20, 21 and 23. Intermediates 19 and 23
cannot produce 11. Zwitterion 20 might lead to 11, but
it is expected to be disfavored for steric reasons. Zwitte-
rion 21 appears to be the most reasonable intermediate
that probably arises from the hetero-Diels–Alder addi-
tion of SO2 to 9, producing sultine 24ꢁ24% or its diastereo-
mer with trans SꢁO and BnO groups. The boat conformer
24 of the sultine intermediate is expected to be ionized
into 21 that adds to 10, or alternatively, 24 adds directly
to 10 producing 22, then 11 (Scheme 3). The formation
of 12 is explained by invoking a stereoselective retro-ene
elimination of SO2 from the sulfinic acid intermediate 25
as for the other cases already discussed.1 This hypothesis
is now firmly confirmed by the establishment of the
relative configuration of 11, and thus of intermediate 25.
References
1. Roulet, J.-M.; Puhr, G.; Vogel, P. Tetrahedron Lett.
1997, 38, 6201.
2. Complete data have been deposited with the Cambridge
Crystallographic Data Centre for 11: CDCC 140985;
27: CDCC 140983; 28: CDCC 140984.
3. Myles, D. C.; Bigham, M. H. Org. Synth. 1992, 70, 231
and references cited therein.
4. Selected data for 11: mp 101.5–103°C; 1H NMR (400
MHz, CDCl3) lH 7.35–7.27 (5H), 5.37 (dq, 1H, 3J 11.0
4J 1.4, H-7), 4.83 (dd, 1H, 3J 6.7, 6.2, H-5), 4.47–4.39
3
(m, 2H), 4.33 (dq, 1H, J 11.0, 6.7, H-8), 3.00 (dd, 1H,
3J 11.0, 6.7, H-4), 2.81 (s, 3H), 2.72 (dd, 1H, 3J 11.0,
6.2, H%-4), 1.84 (d, 3H, 3J 1.4), 1.42 (d, 3H, 3J 6.7,
H-9), 1.12 (s, 9H).
1
5. Data for 12: colorless oil, H NMR (400 MHz, CDCl3)
lH 7.34–7.24 (m, 5H), 5.47–5.36 (m, 2H), 4.52 (m, 2H),
3.98 (ddd, 1H, 3J 7.6, 4.4, 3.8, H-5), 2.80 (dd, 1H, 2J
17.2, 3J 7.6, H-4), 2.45 (dd, 1H, 2J 17.2, 3J 4.4, H%-4),
2.43 (m, 1H, H-6), 1.67 (d, 3H, 3J 5.4, H-9), 1.12 (s,
3
9H), 1.04 (d, 3H, J 6.9, Me-C(6)).
6. Ferna´ndez, T.; Sua´rez, D.; Sordo, J. A.; Monnat, F.;
Roversi, E.; Estrella de Castro, A.; Schenk, K.; Vogel,
P. J. Org. Chem. 1998, 63, 9490.
7. Roversi, E.; Monnat, F.; Schenk, K.; Vogel, P.; Bran˜a,
P.; Sordo, J. A. Chem. Eur. J. 2000, 6, 1858.
In order to test the generality of the above mechanism
we have reacted diene 9 with enoxysilane 26 and SO2/
Yb(OTf)3 (Scheme 4). After the usual work-up with
Bu4NF and MeI, the two diastereomeric methyl sulfones
278 and 289 were isolated in 29 and 33% yield, respectively
(the other products are polymers). Their structures were
established by X-ray diffraction2 and showed for both of
them 1,4-anti (unlike) relative configurations, in agree-
ment with the mechanism proposed in Scheme 3.
1
8. Data for 27: mp 88–89°C, H NMR (400 MHz, CDCl3)
lH 7.36–7.22 (m, 5H), 5.35 (dq, 1H, 3J 11.0, 4J 1.4,
H-7), 4.52 and 4.39 (2d, 2H, 2J 11.7), 4.34 (d, 1H, 3J
3
9.8, H-5), 4.13 (dq, 1H, J 11.0, 6.6, H-8), 3.03 (dq, 1H,
3J 9.8, 6.7, H-4), 2.85 (s, 3H), 2.53 & 2.32 (2dq, 2J
18.4, 3J 7.2, H-2), 1.84 (d, 3H, 4J 1.4, Me-C(6)), 1.40
3
3
(d, 3H, J 6.6, H-9), 1.24 (d, 3H, J 6.7, Me-C(4)), 0.99
3
(t, 3H, J 7.2, H-1).
1
9. Data for 28: mp 60–61°C, H NMR (400 MHz, CDCl3)
This study confirms the hypothesis that our four
component10,11 synthesis of (Z)-4-alkoxy-1,3-dimethyl-
alk-2-enyl methyl sulfones involves sultine intermediates
arising from the hetero-Diels–Alder addition of 1-oxydi-
enes to SO2 rather than the corresponding more stable
sulfolenes.
lH 7.33–7.20 (m, 5H), 5.60 (dq, 1H, 3J 11.0, 4J 1.5,
H-7), 4.41 and 4.28 (2d, 2H, 2J 11.3), 4.40 (d, 1H, 3J
10.1, H-5), 4.12 (dq, 1H, 3J 11.0, 6.8, H-8), 2.93 (dq,
3
1H, J 10.1, 7.1, H-4), 2.85 (s, 3H), 2.60 and 2.52 (2dq,
2H, J 18.3, J 7.2, H-2), 1.83 (d, 3H, J 1.5, Me-C(6)),
2
3
4
3
3
1.46 (d, 3H, J 6.8, H-9), 1.05 (d, 3H, J 7.2, Me-C(4)),
3
0.99 (t, J 7.1, H-1).
10. Deguin, B.; Roulet., J.-M.; Vogel, P. Tetrahedron Lett.
1997, 38, 6197.
Acknowledgements
11. For an asymmetric version of this reaction, see:
Narkevitch, V.; Schenk, K.; Vogel, P. Angew. Chem.,
Int. Ed. 2000, 39, 1809.
This work was supported by the Swiss National Science
Foundation and the Fonds Herbette (Lausanne).
.
.