An efficient procedure for preparing γ-hydroxy α,β-unsaturated sulfones

Article abstract of DOI:10.1002/(sici)1099-0690(199907)1999:7<1545::aid-ejoc1545>3.0.co;2-n

Chromium(II)-mediated Barbier condensation of β-iodovinyl p- tolylsulfone with aldehydes and β-ionone afforded the title hydroxysulfones in good to excellent yields.

Full text of DOI:10.1002/(sici)1099-0690(199907)1999:7<1545::aid-ejoc1545>3.0.co;2-n

FULL PAPER
An Efficient Procedure for Preparing γ-Hydroxy ␣,β-Unsaturated Sulfones
Thomas Zoller,[a] and Daniel Uguen*[a]
Keywords: Takai–Hiyama–Nozaki–Kishi coupling / Sulfones / β-Ionone
Chromium(II)-mediated Barbier condensation of β-iodovinyl p-tolylsulfone with aldehydes and β-ionone afforded the title
hydroxysulfones in good to excellent yields.
sulfone, which decomposed only very slowly at room tem-
Introduction
perature, with formation of a zinc sulfinate.[14b] Addition-
In the course of an ongoing project concerned with the
generation of the A-B-C ring system of 6-keto steroids by
intramolecular DielsϪAlder reaction,[1] we were faced with
the problem of converting the aldehyde 1 into the keto sul-
fone 2a. A conceivable strategy for executing this trans-
formation was, as summarised in Scheme 1, to convert this
aldehyde into the hydroxysulfone 2b, oxidation of which
would have then furnished 2a.
ally, 2-tributylstannylvinyl phenylsulfone has been prepared
from the corresponding chlorosulfone 4b by a Pd0-catalysed
exchange process.[14a] Thus, it might be envisaged that the
sulfone 4a would undergo the iodineϪnickelϪchromium
exchange that occurs theoretically in any THNK reaction,
and that the resulting organometallic species would have a
sufficiently long lifetime to facilitate an efficient conden-
sation with an aldehyde.
Results and Discussion
Using isobutyraldehyde 5a as a model substrate, the
planned THNK coupling was first attempted under con-
ditions (Table 1, entry 1) that have previously proved ef-
ficient in a related context,[15] the aldehyde and the iodosul-
fone 4a being used in stoichiometric amounts (one mol-
equiv. each). Disappointingly, no trace of the expected
hydroxysulfone 6aa could be detected under these con-
ditions. Since the iodosulfone 4a was completely consumed,
this failure was most probably attributable to a possible
(vide supra) decomposition of a transient β-sulfonylvinyl-
nickel (or -chromium) species. In any event, the use of either
an excess of the aldehyde or a less polar solvent should
favour the desired condensation, which was indeed found
to be the case.
When the aldehyde 5a was used in six-fold excess (entry
2), the target hydroxysulfone 6aa was formed in an encour-
aging 24% yield. The starting iodosulfone 4a was fully con-
sumed, however. A change of solvent from DMSO to DMF
did not significantly modify this result (entry 3), although
the reaction proceeded somewhat more rapidly in the latter
solvent medium.
Next, the use of less polar solvents was examined. With
the aldehyde 5a being still used in large excess, a modest
yield (10%) of the sulfone 6aa was attained after 24 h in
diethyl ether (entry 4), but, promisingly, no side-decompo-
sition of the starting material occurred, the non-reacted
iodosulfone 4a being largely recovered (80%) upon chroma-
tography of the crude reaction product. The 4aϪ5a conden-
sation also proceeded slowly in monoglyme (DME), but, at
higher temperatures (ca. 60°C), an enticing 70% yield of
hydroxysulfone 6aa was obtained after 17 hours.
Scheme 1
A variety of efficient methods have been devised for the
preparation of related 3-hydroxy-1,2-alkenylsulfones,[2Ϫ9] as
a result of their utility in organic synthesis.[10] However,
none of these procedures seemed appropriate for a straight-
forward 1 Ǟ 2b conversion. A possibility might have been
a condensation of 1 with acetylene, followed by treatment
of the resulting propargylic alcohol 3 with p-thiocresol, and
finally oxidation of the vinylic sulfide 2c.[11] Unfortunately,
nucleophilic additions of thiols to parent propargylic al-
cohols are known to proceed with a trans selectivity, thereby
furnishing (Z) adducts; in order to obtain addition products
of (E) configuration free radical conditions are neces-
sary,[11bϪc] which are difficult to apply in the present case
owing to the presence of a 1,3-diene moiety in 3.
These considerations prompted us to explore the coup-
ling of aldehydes with the readily available iodosulfone
4a[12] under the conditions of the TakaiϪHiyamaϪ
NozakiϪKishi (THNK) reaction (Scheme 2).[13] Related β-
halovinylsulfones are known to react with various metallic
species with displacement of the halogen atom.[14] For in-
stance, treatment of a β-iodovinyl phenylsulfone with Zn
powder was shown to afford the corresponding 2-iodozinc
[a]
`
Laboratoire de Synthese Organique, E.C.P.M.,
25, rue Becquerel, F-67087 Strasbourg, France
E-mail: uguen@chimie.u-strasbg.fr
Eur. J. Org. Chem. 1999, 1545Ϫ1550
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0707Ϫ1545 $ 17.50ϩ.50/0
1545

T. Zoller, D. Uguen
FULL PAPER
fone) 7 (27%) by chromatography, the target hydroxysulfone
2b in a 89% yield as a 1:1 (NMR) mixture of diastereomers.
Next, oxidation of 2b into the keto sulfone 2a was exam-
ined, the preliminary optimisation of the reaction con-
ditions was carried out by using first the simpler hydroxy-
sulfone 6aa. Whereas a fairly good yield (77%) was ob-
tained with PCC deposited onto silica gel, as recommended
in related cases,[10bϪ10c] the use of either Swern con-
ditions[16a] or nickel peroxide[16b] proved to be less effective,
the ketone 8 being formed under these conditions in yields
no higher than 34%. The best result was obtained with the
DessϪMartin reagent,[16cϪ16d] use of which led to isolation
of the keto sulfone 8 in high yield (81%). Treatment of the
hydroxysulfone 2b with this reagent afforded the desired ke-
tone 2a almost quantitatively (96%), within a few minutes.
Scheme 2
Table 1. Conditions for the 4aϪ5a condensation
Entry 5a
(mol.
CrCl2
(mol.
NiCl2
(mol.
Solvent Time[a] 6aa yield
(hours) (%)
equiv.) equiv.) equiv.)
1
2
1
6
6
6
6
6
4
1
1
4
10
6
6
6
6
6
6
6
6
4
0.1
DMSO 24
DMSO 24
Ϫ
0.01
0.01
0.01
0.01
0.05
0.05
0.05
0.01
0.01
24
3
DMF
Et2O
DME
THF
THF
THF
THF
THF
4
27
4
24
17[b]
2
10
5
70
6
93
7
4
88[c]
87[c]
93[c]
93
8
4
9
3
10
3
Figure 1
[a]Room temp. Ϫ [b]At 60°C. Ϫ [c]Disulfone 7 formed.
In order to assess the scope of this emerging synthetic
process, THNK condensations of the iodosulfone 4a with
various aldehydes were attempted under the conditions of
entry 10 of Table 1. In each case (Table 2), the expected
coupling product was isolated in high yield, the reaction
being particularly fast with α,β-unsaturated aldehydes, go-
ing then to completion in less than 5 min., virtually as a ti-
tration.
A more dramatic change resulted from the use of THF.
As can be seen in Table 1 (entries 6Ϫ10), the 4aϪ5a coup-
ling proceeded within a few hours in this solvent, leading
to high yields of compound 6aa irrespective of the 5a/4a
ratio. Moreover, the yields did not change significantly by
decreasing the excess of aldehyde (entries 6Ϫ8). When the
4a/5a ratio was fixed to unity (entry 8), side formation of
the dienylsulfone 7, assumed to result from homocoupling
of the iodo sulfone 4a, was noticed, a self-coupling reaction
that could be suppressed in some extent by reducing the
NiII/CrII ratio (compare entries 7 and 10).
Thus, provided the required aldehyde is, as in the case of
5a, both cheaper than chromous chloride and more access-
ible than the sulfone 4a, the most appropriate, practical,
conditions are those corresponding to entry 10 of the Table
1. Clearly, however, should the aldehyde (e.g. 1) be more
elaborate than 4a, the conditions of entry 9, although re-
quiring the use of larger excess of the costly chromous chlo-
ride, will be preferred. Hence, reaction of the aldehyde 1
with a slight excess (ca. 1.3 equiv.) of the iodosulfone 4a
Table 2. Condensation of the sulfones 4 with various aldehydes[a]
Sulfone
Aldehyde
Time
Product, Yield (%)
4a
4a
4a
4a
4b
4a
4b
4a
5b
5c
5d
5e
5e
5f
7 h
6ba, 94
6ca, 96
6da, 80
6ea, 89
6eb, 41
6fa, 91
6fb, 17
6ga, 88
1 d
1 d
5 min
18 h
5 min
18 h
5 min
5f
5g
[a]Under conditions of the entry 10, Table 1.
Attempts to use the chlorosulfone 4b in place of the iodo-
under these conditions gave, after separation of the bis(sul- sulfone 4a proved not to be so rewarding. The mobility of
1546
Eur. J. Org. Chem. 1999, 1545Ϫ1550

An Efficient Procedure for Preparing γ-Hydroxy α,β-Unsaturated Sulfones
FULL PAPER
priate reagent and under an argon atmosphere (diethyl ether, DME,
THF: from sodium/benzophenone; DMSO, DMF: from CaH2;
CH2Cl2: from P4O10). The aldehyde 1[1] and the sulfone 4a[12] were
prepared as described previously. Aldehydes 5a؊g and β-ionone 9
(Fluka) were freshly distilled under a reduced pressure of argon
prior to use. All experiments were performed in flame-dried glass-
ware, under an argon atmosphere, with magnetic stirring. Ϫ TLC
analyses were performed on silica gel, with spot visualisation by
exposure of the plates to UV light (254 nm) or by treatment with
the H2SO4/vanillin reagent. Unless it is otherwise stated, eluent:
the chlorine atom in 4b toward nucleophilic species has
been mentioned previously and it might reasonably have
been hoped that this chlorosulfone would behave similarly
to 4a under the above conditions. Though THNK products
could indeed be obtained with a few unsaturated aldehydes
(i.e. 5e؊f), the yields were invariably lower than those
achieved with 4a. Moreover, longer reaction times were re-
quired and hence the use of this sulfone was not pursued.
The reluctance of common (i.e. dialkyl) ketones to un-
dergo THNK condensation with alkenyl iodides is mani- hexane/AcOEt, 70:30. Ϫ Melting points (uncorrected): Büchi ap-
paratus. Ϫ NMR: Bruker W200 (1H and 13C at 200 and 50 MHz,
respectively); for 1H- and 13C-NMR spectra, CDCl3 as solvent,
CHCl3 (δH ϭ 7.25) and CDCl3 (δC ϭ 77.6) as internal standard. Ϫ
Elemental analyses were performed at the C.N.R.S. microanalysis
laboratory (Strasbourg).
fest[13a] and, not too surprisingly, no hydroxysulfone was
formed upon attempted reaction of 4a with acetone under
the aforementioned conditions. However, the exceptional
rate at which the THNK condensation of 4a with unsatu-
rated aldehydes took place prompted us to examine enones
in this context, β-ionone 9 (Scheme 3) being selected as a
candidate since its reaction would have generated a poten-
tially useful sesquiterpenic synthon.
General Protocol for THNK Condensations: Chromous and nickel
chlorides were weighted into a two-necked flask fitted with a sep-
tum and connected to an argon line via a stopcock. The appropri-
ate solvent (1 mL per 1 mmol of CrCl2) was added with a syringe
and the resulting mixture was thoroughly degassed by performing
the freeze-pump-thaw procedure (three cycles). In a similar manner,
a solution of the iodosulfone 4a (ca. 1 ) and the required aldehyde
was prepared in another, identical, flask, and then introduced, via
a cannula, into the stirred suspension of the reducing species. When
the reaction was complete, as judged by TLC, the reaction mixture
was diluted with ethyl acetate and water, and the aqueous layer was
thoroughly extracted with further ethyl acetate. The pooled organic
extracts were washed successively with saturated (aqueous)
NaHCO3, 10% aqueous NaHSO3, and brine, and then dried
(MgSO4). The residue left after evaporation of the solvents was
then chromatographed on Gudoran (Merck; hexane/AcOEt mix-
tures as eluent).
Scheme 3
Attempted condensation of the sulfone 4a with ketone 9
(four-fold excess) under the same conditions as above was
unsuccessful, the only observed product being the bis(sul-
fone) 7, which was isolated in a 56% yield. Since the ratio
of the rates of the desired and of the unwanted (affording
7) coupling processes is directly related to the aldehyde con-
centration, but is inversely proportional to that of the sul-
fone 4a, it could be surmised that the former process, lead-
ing to 10, would be favoured by maintaining the [4a]/[9]
ratio as low as possible during the overall process. Indeed,
very slow addition, over a period of five days,[17] of a solu-
tion of the sulfone 4a in THF to a mixture of ionone 9
and the reducing species in the same solvent resulted in the
formation of the sensitive hydroxysulfone 10 (67%), which
was easily separated from the sulfone 7 (27%) by chroma-
tography.
trans-2-[(E)-3-Hydroxy-4-tosyl-3-buten-1-yl]-1-[(E)-1-methyl-1,3-
butadien-1-yl]-cyclohexane (2b): A solution of the aldehyde 1
(305 mg; 1.59 mmol) and the sulfone 4a (635 mg; 2.06 mmol) in
THF (4 mL) was added to a stirred mixture of CrCl2 (1.23 g;
9.51 mmol) and NiCl2 (2 mg; 0.02 mmol) in THF (5 mL). After 3
hours, the brown reaction mixture was worked-up in the standard
manner and the crude product was chromatographed to afford suc-
cessively the hydroxysulfone 2b (526 mg; 1.41 mmol; 89%) and the
bis(sulfone) 7 (101 mg; 0.278 mmol; 27%). Ϫ 2b: White crystals;
m.p. 115Ϫ117°C. Ϫ Rf (TLC) ϭ 0.33. Ϫ 1H NMR (two dia-
stereomers): δ ϭ 0.96Ϫ1.99 (m, 12 H), 2.31Ϫ2.45 [m, 1 H, CHϭ
C(CH3)CH], 2.43 (s, 3 H, CH3), 4.42 [m, 1 H, CH(OH)], 4.98 (d,
J ϭ 10 Hz, CϭCHH), 5.09 (d, J ϭ 16.5 Hz, 1 H, CϭCHH), 5.87
[(d, J ϭ 11 Hz, 1 H, HCϭC(CH3)], 6.54 (dd, J ϭ 15, 1.5 Hz, 1 H,
CHSO2), 6.60 (ddd, J ϭ 16.5, 11, 10 Hz, 1 H, CH2CϭCH), 6.91
(ddd, J ϭ 15, 7.5, 4 Hz, 1 H, CHϭCHSO2), 7.31Ϫ7.34 (m, 2 H,
aromatic H), 7.73Ϫ7.77 (m, 2 H, aromatic H). C22H30O3S (374.54).
Ϫ 7: White crystals; m.p. 195Ϫ196°C (CH2Cl2/diisopropyl ether).
Ϫ Rf (TLC) ϭ 0.17. Ϫ 1H NMR: δ ϭ 2.44 (s, 6 H, CH3), 6.7Ϫ6.81
(m, 2 H), 7.10Ϫ7.21 (m, 2 H), 7.34Ϫ7.42 (m, 2 H, aromatic H),
7.73Ϫ7.79 (m, 2 H, aromatic H). Ϫ 13C NMR: δ ϭ 21.7 (CH3),
128.1 (aromatic C), 130.2 (aromatic C), 135.1 (CSO2), 136.1 (aro-
matic C), 139.1 (CϭCHSO2), 145.3 (aromatic C). Ϫ MS (EI): m/z
(%) ϭ 362.1 (6) [Mϩ], 298 (1.3), 223 (1.5), 207 (2.9), 155 (1.6), 139
(100) [p-tolylSO]. Ϫ C18H18O4S2 (362.45): calcd. C 59.65, H 5.01;
found C 59.87, H 5.00.
Conclusion
Aldehydes have been shown to react efficiently with the
iodosulfone 4a under the conditions of the TakaiϪ
HiyamaϪNozakiϪKishi reaction,
a coupling process
which, interestingly, could be extended to β-ionone 9. The
high yield achieved in most cases coupled with the ready
availability of the sulfone 4a and the simplicity of the exper-
imental conditions contribute to make this new procedure
for preparing γ-hydroxy-β-vinylsulfones a valuable alterna-
tive to existing methods.[18]
THNK Condensation of Sulfone 4 with Aldehydes (see Table 2): A
solution of the aldehyde (6.5 mmol) and 4a (or 4b) (1.63 mmol) in
THF (5 mL) was added to a mixture of CrCl2 (6.5 mmol) and
NiCl2 (0.016 mmol) in THF (5 mL).
Experimental Section
General: Anhydrous CrCl2 and NiCl2 (both from Fluka) were used
as received. All solvents used were freshly distilled from an appro-
Eur. J. Org. Chem. 1999, 1545Ϫ1550
1547

T. Zoller, D. Uguen
FULL PAPER
(E)-4-Methyl-1-tosyl-1-penten-3-ol (6aa): White crystals; m.p. NMR: δ ϭ 18.4 (CH3), 21.6 (CH3), 25.7 (C-6), 67.3 (C-3), 123.2
114Ϫ115°C. Ϫ Rf (TLC) ϭ 0.43. Ϫ 1H NMR: δ ϭ 0.91 [d, J ϭ
(C-4), 127.7 (aromatic C), 129.4 (C-1), 129.9 (aromatic C), 137.4
7 Hz, 3 H, CH3CH(CH3)], 0.94 [d, J ϭ 7 Hz, 3 H, CH3CH(CH3)], (aromatic C), 138.3 (C-5), 144.3 (aromatic C), 146.2 (C-2). Ϫ
1.81 (m, 1 H, OH), 1.84 [heptd, J ϭ 7, 2 Hz, 1 H, HC(CH3)2)],
2.43 (s, 3 H, CH3), 4.17Ϫ4.2 [m, 1 H, CH(OH)], 6.59 [dd, J ϭ 15,
2 Hz, 1 H, HCϭCH(SO2)], 6.97 [dd, J ϭ 15, 4 Hz, 1 H, HCϭ
CH(SO2)], 7.31Ϫ7.35 (m, 2 H, aromatic H), 7.74Ϫ7.78 (m, 2 H,
aromatic H). Ϫ 13C NMR: δ ϭ 17.2 (C-5), 18.3 (CH3), 21.6 (CH3),
33.7 (C-4), 75 (C-3), 127.7 (aromatic C), 129.9 (aromatic C), 130.9
(C-1), 137.4 (aromatic C), 144.4 (aromatic C), 146.3 (C-2). Ϫ
C13H18O3S (254.3): calcd. C 61.39, H 7.13; found C 61.25, H 7.14.
C14H18O3S (266.35): calcd. C 63.07, H 6.76; found C 63.01, H 6.92.
(E)-4-Methyl-1-tosyl-1,4-hexadien-3-ol (6ga): White crystals; m.p.
201Ϫ202°C. Ϫ Rf (TLC) ϭ 0.19. Ϫ 1H NMR: δ ϭ 1.54 (t, J ϭ
1 Hz, 3 H, CH3), 1.62 (d, J ϭ 6.5 Hz, 3 H, C-6), 1.79 (m, 1 H,
OH), 2.43 (s, 3 H, CH3), 4.74 [m, 1 H, CH(OH)], 5.59 [qd, J ϭ
6.5, 1 Hz, 1 H, CH(CH3)], 6.62 [dd, J ϭ 15, 2 Hz, 1 H, HCϭ
CH(SO2)], 6.88 [dd, J ϭ 15, 3.5 Hz, 1 H, HCϭCH(SO2)],
7.29Ϫ7.37 (m, 2 H, aromatic H), 7.73Ϫ7.79 (m, 2 H, aromatic H).
(E)-5-Methyl-1-tosyl-1-hexen-3-ol (6ba): White crystals; m.p.
Ϫ
13C NMR: δ ϭ 11.3 (CH3), 13.2 (C-6), 21.5 (CH3), 75.8 (C-3),
1
94Ϫ95°C. Ϫ Rf (TLC) ϭ 0.21. Ϫ H NMR: δ ϭ 0.9 [d, J ϭ 7 Hz, 123.8 (C-5), 127.5 (aromatic C), 129.8 (aromatic C), 130.1 (C-1),
3 H, CH3CH(CH3)], 0.94 [d, J ϭ 7 Hz, 3 H, CH3CH(CH3)], 134.4 (C-4), 137.3 (aromatic C), 144.3 (aromatic C), 146.1 (C-2). Ϫ
1.37Ϫ1.48 (m, 2 H, CH2), 1.69Ϫ1.86 [m, 2 H, HC(CH3)2 plus OH], C14H18O3S (266.35): calcd. C 63.07, H 6.76; found C 63.14, H 6.83.
2.43 (s, 3 H, CH3), 4.36Ϫ4.48 [m, 1 H, CH(OH)], 6.58 [dd, J ϭ 15,
(E,E)-1-Phenylsulfonyl-1,4-hexadien-3-ol (6eb): White needles; m.p.
2 Hz, 1 H, HCϭCH(SO2)], 6.96 [dd, J ϭ 15, 4 Hz, 1 H HCϭ
87Ϫ89°C. Ϫ Rf (TLC) ϭ 0.16. Ϫ 1H NMR: δ ϭ 1.69 [d, J ϭ 6 Hz,
CH(SO2)], 7.31Ϫ7.35 (m, 2 H, aromatic H), 7.73Ϫ7.77 (m, 2 H,
3 H, CH(CH3)], 2.26 (m, 1 H, OH), 4.74Ϫ4.82 [m, 1 H, CH(OH)],
aromatic H). Ϫ 13C NMR: δ ϭ 21.6 (CH3), 21.9 (C-6), 23.2 (CH3),
5.41 [ddq, J ϭ 15, 7, 1.5 Hz, 1 H, HCϭCH(CH3)], 5.74 [dqd, J ϭ
15, 6.5, 1 Hz, 1 H, HCϭCH(CH3)], 6.59 [dd, J ϭ 15, 2 Hz, 1 H,
HCϭCH(SO2)], 6.93 [dd, J ϭ 15, 3.5 Hz, 1 H, HCϭCH(SO2)],
24.5 (C-5), 45.4 (C-4), 68.7 (C-3), 127.7 (aromatic C), 129.7 (C-1),
129.9 (aromatic C), 137.3 (aromatic C), 144.4 (aromatic C), 148 (C-
2). Ϫ C14H20O3S (268.37): calcd. C 62.66, H 7.51; found C 62.76,
7.48Ϫ7.66 (m, 3 H, aromatic H), 7.84Ϫ7.90 (m, 2 H, aromatic H).
H 7.57.
Ϫ
13C NMR: δ ϭ 17.7 (CH3), 71.2 (C-3), 127.6 (aromatic C), 129.3
(E)-3-Phenyl-1-tosyl-1-propen-3-ol (6ca): White crystals; m.p.
136Ϫ138°C. Ϫ Rf (TLC) ϭ 0.15. Ϫ 1H NMR: δ ϭ 2.36 (d, J ϭ
(aromatic C), 129.4 (C-1, C-5), 130.3 (C-4), 133.4 (aromatic C),
140.2 (aromatic C), 146.6 (C-2). Ϫ C12H14O3S (238.30): calcd. C
3.5 Hz, 1 H, OH), 2.44 (s, 3 H, CH3), 5.34 [m, 1 H, HC(OH)], 6.73 60.43, H 5.87; found C 60.14, H 5.59.
[dd, J ϭ 15, 2 Hz, 1 H, HCϭCH(SO2)], 7.03 [dd, J ϭ 15, 4 Hz, 1
(E)-5-Methyl-1-phenylsulfonyl-1,4-hexadien-3-ol (6fb): Colourless
oil. Ϫ Rf (TLC) ϭ 0.12. Ϫ H NMR: δ ϭ 1.71 (s, 3 H, CH3), 1.73
H, HCϭCH(SO2)], 7.21Ϫ7.37 (m, 7 H, aromatic H), 7.71Ϫ7.76
(m, 2 H, aromatic H). Ϫ 13C NMR: δ ϭ 21.6 (CH3), 72.8 (C-3),
126.7 (aromatic C), 127.8 (aromatic C), 128.8 (C-1), 129.0 (aro-
matic C), 129.9 (aromatic C), 137.2 (aromatic C), 139.8 (aromatic
C), 144.5 (aromatic C), 145.8 (C-2). Ϫ C16H16O3S (288.4): calcd.
C 66.58, H 5.55; found C 66.42, H 5.27.
1
(s, 3 H, C-6), 2.03 (m, 1 H, OH), 5.06 [m, 2 H, CϭCHϪCH(OH)],
6.59 [dd, J ϭ 15, 1 Hz, 1 H, HCϭCH(SO2)], 6.90 [dd, J ϭ 15,
3.5 Hz, 1 H, HCϭCH(SO2)], 7.48Ϫ7.65 (m, 3 H, aromatic H),
7.85Ϫ7.90 (m, 2 H, aromatic H). Ϫ 13C NMR: δ ϭ 18.4 (CH3),
25.70 (C-6), 67.5 (C-3), 123.1 (C-4), 127.60 (aromatic C), 129.00
(C-1), 129.3 (aromatic C), 133.40 (aromatic C), 138.40 (C-5), 140.30
(E)-3-(4-Methoxyphenyl)-1-tosyl-1-propen-3-ol
(6da):
White
1
needles; m.p. 126Ϫ127°C. Ϫ Rf (TLC) ϭ 0.12. Ϫ H NMR: δ ϭ (aromatic C), 146.80 (C-2). Ϫ C13H16O3S (252.3): calcd. C 61.83,
2.12 (d, J ϭ 3.5 Hz, 1 H, OH), 2.44 (s, 3 H, CH3), 3.81 (s, 3 H,
OCH3), 5.32Ϫ5.37 [m, 1 H, HC(OH)], 6.72 [dd, J ϭ 15, 2 Hz, 1
H, HCϭCH(SO2)], 6.84Ϫ6.92 (m, 2 H, aromatic H), 7.02 [dd, J ϭ
15, 3.5 Hz, 1 H, HCϭCH(SO2)], 7.17Ϫ7.24 (m, 2 H, aromatic H),
7.31 Ϫ7.35 (m, 2 H, aromatic H), 7.74Ϫ7.86 (m, 2 H, aromatic
H). Ϫ 13C NMR: δ ϭ 21.6 (CH3), 55.5 (OCH3), 72.4 (C-3), 114.4
(aromatic C), 127.8 (aromatic C), 128.2 (aromatic C), 129.8 (C-1),
129.9 (aromatic C), 131.9 (aromatic C), 137.3 (aromatic C), 144.4
(aromatic C), 145.9 (C-2), 160 (aromatic C). Ϫ C17H18O4S (318.4):
calcd. C 64.13, H 5.70; found C 64.25, H 5.78.
H 6.34; found C 62.14, H 6.23.
(E,E)-3-Methyl-1-tosyl-5-[2,6,6-trimethyl-1-cyclohexen-1-yl]-1,4-
pentadien-3-ol (10): A solution of sulfone 4a (500 mg; 1.62 mmol)
in THF (5 mL) was periodically added dropwise to a mixture of
CrCl2 (1.26 g, 9.74 mmol), NiCl2 (2 mg; 0.02 mmol), and β-ionone
9 (1.25 g, 6.49 mmol) in THF (5 mL) over a period of 5 days. The
mixture was stirred for a further 2 days and then worked-up as
above, the organic extract being filtered through Celite (AcOEt)
prior drying. Chromatography of the residue left upon evaporation
of the solvents afforded successively the hydroxysulfone 10 and the
bis(sulfone) 7 (83 mg). Recrystallisation of 10 from cold diethyl
(E,E)-1-Tosyl-1,4-hexadien-3-ol (6ea): Colourless oil. Ϫ Rf (TLC) ϭ
0.13. Ϫ 1H NMR: δ ϭ 1.69 [ddd, J ϭ 6.5, 1.5, 0.5 Hz, 3 H,
CH(CH3)], 2.34 (m, 1 H, OH), 2.42 (s, 3 H, CH3), 4.76 [m, 1 H, m.p. 89Ϫ90°C. Ϫ Rf (TLC) ϭ 0.29 (hexane/AcOEt, 80:20). Ϫ H
CH(OH)], 5.41 [ddq, J ϭ 15, 5, 1.5 Hz, 1 H, HCϭCH(CH3)], 5.74 NMR: δ ϭ 0.92 [s, 6 H, 6Ј-C(CH3)2], 1.4Ϫ1.62 (m, 4 H, 4Ј-CH2,
ether/hexane afforded white crystals (405 mg; 1.08 mmol; 67%);
1
[dqd, J ϭ 15, 6.5, 1 Hz, 1 H, HCϭCH(CH3)], 6.57 [dd, J ϭ 15,
2 Hz, 1 H, HCϭCH(SO2)], 6.89 [dd, J ϭ 15, 4 Hz, 1 H, HCϭ
5Ј-CH2), 1.48 (s, 3 H, 2Ј-CCH3), 1.59 (splitted s, 3 H, 3-CCH3),
1.74 (s, 1 H, OH), 1.96 (t, J ϭ 6 Hz, 2 H, 3Ј-CH2), 2.43 (s, 3 H,
CH(SO2)], 7.29Ϫ7.33 (m, 2 H, aromatic H), 7.71Ϫ7.77 (m, 2 H, CH3), 5.47 (d, J ϭ 16 Hz, 1 H, 5-CH), 6.07 (dd, J ϭ 16, 0.5 Hz, 1
aromatic H). Ϫ 13C NMR: δ ϭ 17.8 (CH3), 21.7 (CH3), 71.2 (C-
H, 4-CH), 6.60 [d, J ϭ 15 Hz, 1 H, CHϭCH(SO2)], 6.99 [d, J ϭ
3), 127.8 (aromatic C), 129.6 (C-1, C-4), 130 (C-5, aromatic C), 15 Hz, 1 H, CHϭCH(SO2)], 7.29Ϫ7.33 (m, 2 H, aromatic H),
137.2 (aromatic C), 144.6 (aromatic C), 146.5 (C-2). Ϫ C13H16O3S
(252.3): calcd. C 61.82, H 6.34; found C 61.80, H 6.29.
7.73Ϫ7.77 (m, 2 H, aromatic H). Ϫ 13C NMR: δ ϭ 19.1 (C-4Ј),
21.3 (CH3), 21.6 (CH3-C-2Ј), 27.9 (CH3-C-3), 28.7 [(CH3)2C-6Ј],
32.7 (C-3Ј), 34.00 (C-6Ј), 39.13 (C-5Ј), 73.2 (C-3), 127.7 (aromatic
C), 128.2 (C-5), 128.6 (C-1), 129.5 (C-1Ј, C-2Ј), 129.9 (aromatic C),
136.3 (C-6), 137.5 (aromatic C), 144.4 (aromatic C), 149.8 (C-2). Ϫ
C22H30O3S (374.53).
(E)-5-Methyl-1-tosyl-1,4-hexadien-3-ol (6fa): White crystals; m.p.
116Ϫ117°C. Ϫ Rf (TLC) ϭ 0.13. Ϫ 1H NMR: δ ϭ 1.7 (s, 3 H,
CH3), 1.73 (s, 3 H, C-6), 1.98 (m, 1 H, OH), 2.42 (s, 3 H, CH3),
5.06 [m, 2 H, CϭCHϪCH(OH)], 6.56 [dd, J ϭ 15, 1 Hz, 1 H, HCϭ
CH(SO2)], 6.86 [dd, J ϭ 15, 1.5 Hz, 1 H, HCϭCH(SO2)], 7.3Ϫ7.4 (E)-4-Methyl-1-tosyl-1-penten-3-one (8). ؊ Oxidation of 6aa with
(m, 2 H, aromatic H), 7.73Ϫ7.77 (m, 2 H, aromatic H). Ϫ 13C
the Dess؊Martin Reagent: A solution of the hydroxysulfone 6aa
1548
Eur. J. Org. Chem. 1999, 1545Ϫ1550

An Efficient Procedure for Preparing γ-Hydroxy α,β-Unsaturated Sulfones
FULL PAPER
[4]
From β,γ-epoxysulfones: [4a] A. D. Westwell, M. Thornton-Pett,
C. M. Rayner, J. Chem. Soc., Perkin Trans. 1I 1995, 847Ϫ859.
(50 mg; 0.2 mmol) in CH2Cl2 (2 mL) was prepared in a three-
necked flask fitted with a septum and a tube containing the Des-
[4b]
Ϫ
D. K. Hutchinson, P. L. Fuchs, J. Am. Chem. Soc. 1985,
[4c]
sϪMartin periodinane (DMP), and connected to an argon line. The
DMP reagent was gradually added to the solution at room temp.,
with gentle stirring. The solid slowly dissolved and the resulting
clear solution was subsequently stirred for a further 20 min. A mix-
ture of diethyl ether (2 mL) and of a solution of NaHSO3 (146 mg;
0.59 mmol) and NaHCO3 (38 mg; 0.45 mmol) in water (0.5 mL)
was then added with a syringe, and the resulting mixture was vigor-
ously stirred until two well-defined layers were obtained. The aque-
ous phase was thoroughly extracted with diethyl ether (3ϫ 20 mL),
and the pooled organic extracts were washed with saturated
NaHCO3 (20 mL) and brine (20 mL), then dried (MgSO4), and the
solvents were evaporated. Filtration of the resulting residue on sil-
ica gel (AcOEt) afforded, after evaporation of the solvents, the pure
keto sulfone 8 (41 mg; 0.162 mmol; 81%) as a white solid; m.p.
98Ϫ99°C. Ϫ Rf (TLC): ϭ 0.58 (hexane/AcOEt, 50:50). Ϫ 1H
NMR: δ ϭ 1.08 [d, J ϭ 7 Hz, 6 H, CH(CH3)2], 2.39 (s, 3 H, CH3),
2.77 [hept, J ϭ 1 H, CH(CH3)2], 7.13 [s, 2 H, HCϭCH(SO2)],
7.30Ϫ7.34 (m, 2 H, aromatic H), 7.72Ϫ7.76 (m, 2 H, aromatic H).
107, 6137Ϫ6138. Ϫ
J. C. Sadler, R. E. Hutchinson, P. L.
[4d]
Fuchs, J. Am. Chem. Soc. 1981, 103, 2110Ϫ2112. Ϫ
J. C.
Sadler, P. L. Fuchs, J. Am. Chem. Soc. 1981, 103, 2112Ϫ2114.
Ϫ
[4e]
J. E. Bäckvall, S. K. Juntunen, J. Org. Chem. 1988, 53,
[4f]
2398Ϫ2400. Ϫ
T. Sakakibara, I. Takai, A. Yamamoto, H.
Iizuka, K. Hirasawa, Y. Ishido, Tetrahedron Lett. 1990, 31,
[4g]
3749Ϫ3752. Ϫ
Y. Pan, S. A. Hardinger, P. L. Fuchs, Synth.
[4h]
Commun. 1989, 19, 403Ϫ416. Ϫ
S. A. Hardinger, P. L.
Fuchs, J. Org. Chem. 1987, 52, 2739Ϫ2749. Ϫ [4i] O. Arjona, R.
F. de la Pradilla, A. Mallo, J. Plumet, A. Viso, Tetrahedron Lett.
[4j]
1990, 31, 1475Ϫ1478. Ϫ
J. Adrio, J. C. Carretero, R. G. Ar-
[4k]
`
rayas, Synlett 1996, 640Ϫ642. Ϫ
A. K. Maiti, P. Bhattach-
[4l]
aryya, Tetrahedron 1994, 50, 10483Ϫ10490. Ϫ
P. Bhattach-
aryya, G. K. Biswas, Synth. Commun. 1991, 21, 569Ϫ573. Ϫ
[4m]
J. K. Crandall, C. Pradat, J. Org. Chem. 1985, 50,
[4n]
1327Ϫ1329. Ϫ
C. C. J. Culvenor, W. Davies, W. E. Savige,
[4o]
J. Chem. Soc. 1949, 1419Ϫ1423. Ϫ
A. M. Bernard, M. T.
Cocco, C. Congiu, G. L. Franzone, P. P. Piras, Synthesis 1996,
[4p]
361Ϫ366. Ϫ
B. M. Trost, M. G. Organ, G. A. OЈDoherty,
[4q]
J. Am. Chem. Soc. 1995, 117, 9662Ϫ9670. Ϫ
S. W. Lee, P.
L. Fuchs, Tetrahedron Lett. 1991, 32, 2861Ϫ2864.
[5]
[6]
From 1-arylsulfonyl propargylic alcohols: I. Ryu, N. Kusumoto,
A. Ogawa, N. Kambe, N. Sonoda, Organometallics 1989, 8,
2279Ϫ2281.
Ϫ
13C NMR: δ ϭ 17.4 [(CH3)2C], 21.5 (CH3), 40.6 (C-4), 128.1
(aromatic C), 130.1 (aromatic C), 133.8 (C-2), 135.5 (aromatic C),
140.6 (C-1), 145.4 (aromatic C), 201.0 (C-3 ). Ϫ C13H16O3S
(252.32): calcd. C 61.83, H 6.34; found C 61.94, H 6.59.
From 2-hetero-substituted 3-hydroxyalkylsulfones and O-de-
[6a]
rivatives:
405Ϫ406. Ϫ
875Ϫ877. Ϫ
S.-K. Kang, J. Chem. Soc., Perkin Trans. 1I 1992,
[6b]
D. Quiu, R. R. Schmidt, Synthesis 1990,
[6c]
N. J. Barnes, A. H. Davidson, L. R. Hughes,
trans-1-[(E)-1-Methyl-1,3-butadien-1-yl]-2-[(E)-3-oxo-4-tosyl-3-
buten-1-yl]cyclohexane (2a): Using the protocol described above for
the 6aa Ǟ 8 conversion, the alcohol 2b (480 mg; 1.28 mmol) was
likewise treated with the DessϪMartin periodinane (924 mg;
2.18 mmol) to give the keto sulfone 2a (458 mg; 1.22 mmol; 96%)
as a white solid; m.p. 55°C (dec.). Ϫ Rf (TLC) ϭ 0.47. Ϫ 1H NMR:
δ ϭ 0.96Ϫ2.06 (m, 12 H), 2.19 [dd (A part of an ABX system),
JAB ϭ 16.5 Hz, JAX ϭ 8 Hz, 1 H, 1Љ-CH], 2.37 (td, J ϭ 10.5,
4 Hz, 1 H, 2Ј-CH), 2.45 (s, 3 H), 2.55 [dd (B part of an ABX
system), JAB ϭ 16.5 Hz, JBX ϭ 4 Hz, 1 H, 1Љ-CH], 5.00 (dd, J ϭ
10.0, 2 Hz, 1 H, HHCϭC), 5.07 (dd, J ϭ 16.5, 2 Hz, 1 H, HHCϭ
C), 5.82 [d, J ϭ 11 Hz, 1 H, HCϭC(CH3)], 6.60 (ddd, J ϭ 16.5,
11, 10 Hz, 1 H, HCϭCH2), 6.91 (d, J ϭ 15 Hz, 1 H, 3ЈЈ-CH), 7.05
(d, J ϭ 15 Hz, 1 H, 4ЈЈ-CH), 7.34Ϫ7.39 (m, 2 H, aromatic H),
7.75Ϫ7.79 (m, 2 H, aromatic H). Ϫ 13C NMR: δ ϭ 19.4 [(CH3)C-
1Ј], 21.7 (C-4, C-5), 30.7 (C-6), 33 (C-3), 35.8 (C-2), 44.9 (C-1),
47.5 (C-1Љ), 116 (C-4Ј), 128.3 (aromatic C), 128.6 (C-2Ј), 130.2 (aro-
matic C), 132.00 (C-3Ј), 135.6 (aromatic C), 135.7 (C-3Љ), 140.1 (C-
4Љ), 141.6 (C-1Ј), 145.5 (aromatic C), 197.4 (C-6Љ). Ϫ C22H28O3S
(375.52).
G. Procter, J. Chem. Soc., Chem. Commun. 1985, 1292Ϫ1294.
Ϫ
[6d] S. G. Pyne, D. C. Spellmeyer, S. Chen, P. L. Fuchs, J. Am.
[6e]
Chem. Soc. 1982, 104, 5728Ϫ5740. Ϫ
J. F. Cassidy, J. M.
[6f]
Williams, Tetrahedron Lett. 1986, 27, 4355Ϫ4538. Ϫ
D. K.
Hutchinson, S. A. Hardinger, P. L. Fuchs, Tetrahedron Lett.
[6g]
1986, 27, 1429Ϫ1432. Ϫ
D. K. Hutchinson, P. L. Fuchs,
[6h]
`
C. Najera, A.
Tetrahedron Lett. 1986, 27, 1425Ϫ1428. Ϫ
´
Perez-Pinar, J. M. Sansano, Tetrahedron 1991, 47, 6337Ϫ6352.
Ϫ [6i] C. Najera, B. Baldo, M. Yus, J. Chem. Soc., Perkin Trans.
1I 1988, 1029Ϫ1032. Ϫ [6j] S. Sengupta, D. Sen Sarma, S. Mon-
dal, Tetrahedron: Asymmetry 1998, 2311Ϫ2316.
`
`
[7]
[8]
From allylic bis(sulfones): T. Cuvigny, K. Du Penhoat, M. Julia,
Rec. Trav. Chim. Pays-Bas 1986, 105, 409Ϫ421.
From vinyl arylsulfones:
Quiclet-Sire, M. Samadi, Tetrahedron:Asymmetry 1994, 5, 2123
Ϫ2136. Ϫ [8b] D. H. R. Barton, A. Gateau-Olesker, S. D. Gero,
B. Lacher, C. Tachdjian, S. Z. Zard, Tetrahedron 1993, 49,
4589Ϫ4602.
[8a]
D. H. R. Barton, S. D. Gero, B.
[9]
From α-oxygenated aldehydes: S. F. Wnuk, N. K. Dalley, M.
Robins, Can. J. Chem. 1991, 69, 2104Ϫ2111.
[10] [10a]
E. Dominguez, J. C. Carretero, Tetrahedron 1994, 50,
[10b]
7557Ϫ7566. Ϫ
J. C. Carretero, E. Dominguez, J. Org.
Chem. 1993, 58, 1596Ϫ1600. Ϫ [10c] F. M. Leon, J. C. Carretero,
[10d]
Tetrahedron Lett. 1991, 32, 5405Ϫ5408. Ϫ
M. Isobe, Y.
Ichikawa, Y. Funabashi, S. Mio, T. Goto, Tetrahedron 1986, 42,
[10e]
2863Ϫ2872. Ϫ
M. Kitamura, M. Isobe, Y. Ichikawa, T.
[10f]
Goto, J. Am. Chem. Soc. 1984, 106, 3252Ϫ3257. Ϫ
M.
Acknowledgments
Isobe, Y. Ichikawa, H. Masaki, T. Goto, Tetrahedron Lett. 1984.
[10g]
25, 3607Ϫ3610. Ϫ
P. L. Fuchs, T. F. Braish, Chem. Rev.
[10h]
´
Thanks are due to the C.N.R.S. and the Conseil Regional dЈAlsace
1986, 86, 903Ϫ917. Ϫ
J. Adrio, J. C. Carretero, R. G. Ar-
rayas, Synlett 1996, 640Ϫ642. Ϫ [10i] R. Noyori, M. Suzuki, An-
for a grant (to T. Z.), and to Miss Sylviane Abdi for assistance in
performing some of the coupling experiments.
`
gew. Chem. Int. Ed. Engl. 1984, 23, 847Ϫ876, and references
[10j]
cited therein. Ϫ
B. M. Trost, P. Seoane, S. Mignani, M.
[10k]
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[1]
Alonso, J. L. Garrido, V. Magro, C. Pedregal, J. Org. Chem.
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[10l]
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J. C. Carretero, E. Dominguez, J.
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[3]
[2a]
From sulfinylmethyl arylsulfones:
E. Dominguez, J. C. Car-
[2b]
retero, Tetrahedron Lett. 1990, 31, 2487Ϫ2490. Ϫ
B. M.
[2c]
Trost, T. A. Grese, J. Org. Chem. 1991, 56, 3189Ϫ3192. Ϫ
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[11b]
C. Mercier, Doctorate dissertation, Paris VI, 1984. Ϫ
Trans. 1I 1995, 149Ϫ156, and quoted references therein.
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[3a]
[11c]
From allylic sulfones:
G. S. Ananda, P. J. Crenins, R. J.
C. Mercier, M. Julia, D. Uguen, unpublished results. For
Stoodley, J. Chem. Soc., Chem. Commun. 1987, 882 and quoted
instance, (Z)-3-methyl-1-(p-tolylthio)-1-buten-3-ol, which is
formed exclusively upon treatment of 3-methyl-1-butyne-3-ol
with p-thiocresol in basic, protic media and under strictly an-
aerobic conditions, was shown to give, besides a small amount
of its regioisomer [i.e. 3-methyl-2-(p-tolylthio)-1-buten-3-ol], the
[3b]
references therein. Ϫ
K. Ogura, N. Shibuya, H. Iida, Tetra-
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Eur. J. Org. Chem. 1999, 1545Ϫ1550
1549

T. Zoller, D. Uguen
FULL PAPER
[16] [16a]
stereomeric (E)-hydroxysulfide upon treatment with traces of p-
J. R. Parikh, W. von E. Doering, J. Am. Chem. Soc. 1967,
[16b]
thiocresol and either AIBN or oxygen, in dichloromethane.
89, 5505Ϫ5507. Ϫ
J. Org. Chem. 1962, 27, 1597Ϫ1601. Ϫ
K. Nakagawa, R. Konaka, T. Nakata,
[12]
[16c]
T. Zoller, D. Uguen, Tetrahedron Lett. 1998, 39, 8089Ϫ8092.
D. B. Dess, J. C.
[16d]
[13] [13a]
K. Takai, K. Kimura, T. Kuroda, T. Hiyama, H. Nozaki,
Martin, J. Org. Chem. 1983, 48, 4155Ϫ4156. Ϫ
S. M. Ru-
[13b]
Tetrahedron Lett. 1983, 24, 5281Ϫ5284. Ϫ
K. Kishi, Pure
bistein, R. M. Williams, J. Org. Chem. 1995, 60, 7215Ϫ7223.
Due to the sensitivity of the aldehyde 1, which decomposes
within a few days on standing at room temperature, execution
of the 1Ϫ4a condensation by us did not proceed satisfactorily
under these conditions.
[13c]
[17]
[18]
Appl. Chem. 1992, 64, 343Ϫ350, and references therein. Ϫ
For a review, see: P. Cintas, Synthesis 1992, 248Ϫ257; L. A.
Luger, A. Wessjohann, G. Scheid Synthesis, 1999, 1Ϫ36.
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[14b]
Ϫ
C. J. Rao, P. Knochel, J. Org. Chem. 1991, 56,
The results presented herein are taken in part from the Doctor-
ate dissertation of Thomas Zoller and have been presented in
brief at the symposium on the “Impact of Organic Synthesis on
Drug Discovery”, University of Heidelberg, September 6Ϫ8th,
1998.
[14c]
4593Ϫ4596. Ϫ
Lett. 1983, 24, 4025Ϫ4028. Ϫ
P. L. Fuchs, J. Am. Chem. Soc. 1996, 118, 4284Ϫ4290. Ϫ
W. E. Truce, A. W. Borel, P. J. Marek, J. Org. Chem. 1976,
41, 401Ϫ402.
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[14d]
J. S. Xiang, A. Mahadevan,
[14e]
Received November 18, 1998
[15]
G. Oddon, D. Uguen, Tetrahedron Lett. 1998, 39, 1157Ϫ1160.
[O98521]
1550
Eur. J. Org. Chem. 1999, 1545Ϫ1550