Enantiomerically pure cis- and trans-2-substituted cyclopropanols from allylic sulfones

Article abstract of DOI:10.1055/s-2003-36256

Enantiomerically pure cis- and trans-2-substituted cyclopropanols have been obtained from allylic sulfones derived from (R)-glyceraldehyde, in good yields.

Full text of DOI:10.1055/s-2003-36256

PAPER
53
Enantiomerically Pure cis- and trans-2-Substituted Cyclopropanols from
Allylic Sulfones
C
yclopropanolsfr
a
A
llylic
vSulfones id Díez,* Pilar García, Isidro S. Marcos, Narciso M. Garrido, Pilar Basabe, Julio G. Urones
Dpto. de Química Orgánica, Universidad de Salamanca, Plaza de los Caídos 1–5, 37008 Salamanca, Spain
Fax +34(923)294574; E-mail: ddm@usal.es
Received 24 July 2002
compound reacts selectively with p-toluenesulfonyl
chloride in pyridine to give 5, which was transformed un-
der the usual conditions of protection and substitution into
iodide 6.6 In order to obtain the different iodides, com-
pound 6 was protected as its THP, TBDMS, and
C(CH3)2(OCH3),7 derivatives (13, 16 and 17 respective-
ly). The MOM derivative was better prepared by protec-
tion of the tosylate 5 to give 11, followed by conversion to
iodide 14 (Scheme 2).
Abstract: Enantiomerically pure cis- and trans-2-substituted cy-
clopropanols have been obtained from allylic sulfones derived from
(R)-glyceraldehyde, in good yields.
Key words: cyclopropanols, sulfones, cyclization, synthesis
1,2-disubstituted cyclopropanes can be found in natural
and biologically active molecules.1 Therefore, and be-
cause of their unique reactivity2 the development of an
asymmetric approach to these rings is of considerable in-
terest. Among cyclopropanes, disubstituted cyclopro-
panols are quite rare, and their chemistry offers great
potential3 especially in the case of vinylic substituents.4
The benzyl derivative 15 was made from diol 4 by protec-
tion under the usual conditions to yield the acetal 7. Re-
duction was attempted under a variety of conditions, with
NaCNBH3 TMSCl giving the best results, yielding com-
pounds 8 and 9 in a 1:1 ratio. Compound 8 was trans-
formed into the required 15 as usual by tosylation and
reaction of the corresponding tosylate 12 with sodium io-
dide.
As part of our program on the elimination reaction of al-
lylic sulfones such as 1, we have found that, if the same
protecting group is used for both hydroxyl groups,5 these
compounds give rise to 1-hydroxymethyl-4-sulfonylbuta-
dienes (Scheme 1).
Once the starting materials 13 17 had been obtained, they
were treated separately with LDA as base. In a recent pa-
per, we showed that if the secondary alcohol was protect-
ed as its tetrahydropyranyl derivative, then treatment
under basic conditions led to the protected cyclopropanes
in good yield as a 70:30 mixture of 18 and 19.6 The same
ratio was observed using 1.0 or 1.5 equivalents of LDA,
but a better yield was achieved in the latter case
(Scheme 3).
Here we show that this reaction can be extended to other
protecting groups that add more versatility to our method-
ology. Treatment of compounds 13 17 with LDA as base
led to the desired cyclopropanes in different, even re-
versed diastereomeric ratios, depending on the protecting
group.
Scheme 1
In a recent paper, we differentiated the two hydroxyl
groups.6 The primary hydroxyl group was converted into
a good leaving group (iodide) and the secondary one pro-
tected with a very stable group (tetrahydropyranyl). The
stereogenic center was preserved in order to obtain cyclo-
propanols in enantiomerically pure form instead of dienes,
in the above reaction. To extend the methodology, several
protecting groups were tested, and the best conditions for
obtaining enantiomerically enriched cyclopropanes are
reported here.
The configuration of the double bond in all vinylcyclopro-
panes was assigned according to the coupling constant of
its vicinal hydrogens (3J = 15.0 Hz).6 The ratio of the dia-
stereomeric cyclopropanes formed can be rationalized on
the basis of the competition between the bulkiness of the
protecting group, the chelating effect between the neigh-
boring oxygenated group and the 1-sulfonylallyllithium
intermediate with delocalization of the partial negative
charge (Scheme 3).8
Compound 1, previously synthesized by us,5 was depro-
tected with 2 N HCl in methanol, to yield diol 4. This
Deprotection under acidic conditions of 18 led to alde-
hyde 28 (Scheme 4). For this reason it was decided to hy-
drogenate first and then deprotect to obtain the required
cyclopropanols.
Synthesis 2003, No. 1, 30 12 2002. Article Identifier:
1437-210X,E;2003,0,01,0053,0062,ftx,en;P04002SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

54
D. Díez et al.
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Scheme 2 Reagents and conditions: (a) HCl 2N, MeOH, r.t.; (b) TsCl, pyridine, r.t., (c) NaI, acetone, 80 ºC; (d) p-MeOC6H4CH(OMe)2,
TsOH, PhH, 130 ºC; (e) NaCNBH3, TMSCl, MeCN, r.t.; (f) DHP, TsOH, CH2Cl2, r.t.; (g) CH2(OCH3)2, P2O5, CHCl3, r.t.; (h) TBDMSOTf,
2,6-lutidine, THF, r.t.; (i) 2-methoxypropene, PPTS, r.t.
Scheme 3
stants J1 2 = 2.8 Hz for 30, J1 2 = 6.4 Hz for 35, and exten-
sive NOE studies.
In conclusion, we have developed a convenient method
for the synthesis of enantiomerically pure cis- and trans-
2-substituted cyclopropanols with great synthetic poten-
tial. It is necessary to differentiate the two hydroxy groups
of the 5-benzenesulfonyl-pent-3-ene-1,2-diol (4), to ob-
Scheme 4
tain the desired cyclopropanols on treatment with base,
While compounds 18 25 were hydrogenated giving satu-
rated protected cyclopropanols 29, 31 33, 34, 36 38
which were subsequently deprotected separately to yield
30 and 35, compound 26 gave compound 30 directly on
hydrogenation. Compound 27 decomposed, possibly due
to steric encumbrance of the double bond (Scheme 5).
since undifferentiated protection of both hydroxyl groups
led to elimination of the protecting group and diene for-
mation.
1H NMR spectra were recorded in CDCl3 (ref. = 7.26) at 200 and
400 MHz on Varian 200 VX and BRUKER DRX 400 instruments,
respectively. 13C NMR spectra were recorded in CDCl3 (ref.
= 77.0) at 50 and 100 MHz on Varian 200 VX and BRUKER
DRX 400 instruments, respectively, and multiplicities were deter-
mined by DEPT experiments. IR spectra were registered on a
The configuration of these compounds was determined
from the 1H NMR spectra on the basis of the coupling con-
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York

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Cyclopropanols from Allylic Sulfones
55
Scheme 5 Reagents and conditions: (a) H2, PtO2, EtOAc; (b) TsOH, MeOH; (c) THF–H2O–HCl 6M 1:5:2; (d) H2, Pd/C, EtOAc; (e) TBAF,
THF.
BOMEM 100 FT IR spectrophotometer. Optical rotations were de-
termined using a Perkin-Elmer 241 polarimeter and 1 dm cells. The
electron impact (EI) mass spectra were run on a VG-TS 250 spec-
trometer at 70 eV ionizing voltage. HRMS were recorded in a VG
Platform (Fisons) spectrometer using Chemical Ionization (ammo-
nia as gas) or Fast Atom Bombardment (FAB) technique. Column
chromatography was performed with Merck silica gel 60 (70–230
mesh). Solvents and reagents were generally distilled immediately
prior to use: THF from sodium benzophenone ketyl; CH2Cl2 and di-
isopropylamine from CaH2; pyridine from KOH.
(–)-(2S)- 5-Benzenesulfonyl-1-tosyloxy-pent-3-ene-2-ol (5)
To a soln of 4 (0.83 g, 3.44 mmol) in pyridine (5 mL) was added
TsCl (0.66 g, 3.44 mmol). The soln was allowed to stir for 16 h, by
which time TLC analysis showed that no starting material re-
mained. Some drops of H2O were added, the soln was poured into a
separating funnel, extracted with Et2O, the organic phase was
washed with a soln of 2 N HCl, H2O, sat. brine, dried with anhyd
Na2SO4, filtered and the solvent removed in vacuo. The resultant oil
was purified by flash silica column chromatography (hexane–
EtOAc, 8:2) to yield 0.95 g (70%) of 5 as a white solid.
[ ]D20 –2.0 (c 0.94, CHCl3).
(–)-(2S)-5-Benzenesulfonyl-pent-3-ene-1,2-diol (4)
To a soln of 1 (1.02 g, 3.62 mmol) in MeOH (10 mL) were added
an aq soln of 2 N HCl (2 mL), the mixture was left to stir for 2 h
before completion. To stop the reaction, an aq soln of Na2CO3
(10%) was added until neutralization occured. The mixture was
poured into an Erlenmeyer with Et2O, dried over anhyd Na2SO4, fil-
tered and the solvent removed in vacuo to give 0.85 g of diol 4 (97%
yield).
IR: 3200–3600, 2924, 1447, 1358, 1308, 1177, 1144, 1086, 974
cm–1.
1H NMR (200 MHz, CDCl3): = 2.45 (3 H, s, CH3-), 2.65 (1 H, br
s, -OH), 3.79 (3 H, m, HA-1, H-5), 3.90 (1 H, dd, J = 3.6, 10.2 Hz,
HB-1), 4.33 (1 H, m, H-2), 5.49 (1 H, dd, J = 5.2, 15.7 Hz, H-3), 5.74
(1 H, m, H-4), 7.36 (2 H, d, J = 8.4 Hz, Hmeta Ts-), 7.58 (3 H, m, -
SO2Ph), 7.81 (4 H, m, Hortho Ts-, -SO2Ph).
[ ]D20 –6.1 (c 0.92, CHCl3).
13C NMR (50 MHz, CDCl3): = 22.0 (CH3-), 59.6 (C-5), 69.5 (C-
2) 72.5 (C-1), 120.1 (C-3), 128.2 (Cortho, Ts-), 128.7 (Cortho
-SO2Ph), 129.5 (Cmeta, -SO2Ph), 130.3 (Cmeta, Ts-), 132.5 (Cipso
Ts-), 134.3 (Cpara, -SO2Ph), 137.2 (C-4), 138.3 (Cipso, -SO2Ph),
145.6 (Cpara, Ts-).
MS: m/z (%) = 397 (10) [M+], 307 (11), 154 (100), 107 (40), 77 (42).
,
,
IR: 3100–3700, 3067, 2924, 2876, 1586, 1447, 1402, 1306, 1240,
1142, 1087, 1026, 974, 889, 772, 739, 689 cm–1.
1H NMR (200 MHz, CDCl3): = 3.31 (1 H, dd, J = 7.0, 11.4 Hz,
HA-1), 3.49 (1 H, dd, J = 3.2, 11.4 Hz, HB-1), 3.76 (2 H, d, J = 7.0
Hz, H-5), 4.16 (1 H, m, H-2), 5.59 (1 H, dd, J = 4.8, 15.4 Hz, H-3),
5.69 (1 H, m, H-4), 7.53 (3 H, m, -SO2Ph), 7.80 (2 H, m, -SO2Ph).
HRMS: m/z calcd for C18H20O6S2, 396.0701; found, 397.0707.
13C NMR (50 MHz, CDCl3): = 59.8 (C-5), 66.1 (C-1), 72.3 (C-2),
118.0 (C-3), 128.6 (Cortho, -SO2Ph), 129.5 (Cmeta, -SO2Ph), 134.3
(Cpara, -SO2Ph), 138.3 (Cipso, -SO2Ph), 140.0 (C-4).
Anal. calcd for C18H20O6S2 (396.5): C, 54.53; H, 5.08; S, 16.18.
Found: C, 54.55; H, 5.18; S, 16.02.
MS: m/z (%) = 243 (9) [M+], 176 (12), 154 (100), 107 (21), 77 (29).
(–)-(2S)-5-Benzenesulfonyl-1-iodo-pent-3-en-2-ol (6)
To a soln of 5 (0.31 g, 0.78 mmol) in acetone (4 mL) was added so-
dium iodide (0.40 g, 2.66 mmol). The soln was refluxed (80 °C) for
5 h under an argon atm, and allowed to cool. The solvent was re-
moved in vacuo. The mixture was dissolved in H2O, Et2O and
poured into a separating funnel. The organic phase was washed with
a sat. soln of Na2S2O3, a soln. of NaHCO3 (5%), H2O, brine, then
dried with anhyd Na2SO4, filtered and the solvent removed in vac-
HRMS: m/z calcd for C11H14O4S, 242.0613; found, 243.0623.
Anal. calcd for C11H14O4S (242.3): C, 54.53; H, 5.82; S, 13.23.
Found: C, 54.53; H, 5.88; S, 13.33.
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56
D. Díez et al.
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uo. The resultant oil was purified by flash silica column chromatog-
raphy (hexane–EtOAc, 8:2) to yield 0.26 g (94%) of 6.
[ ]D20 –6.3 (c 1.30, CHCl3).
13C NMR (50 MHz, CDCl3): = –4.5 (MeA–Si), –4.3 (MeB–Si),
12.2 (C-1), 18.3 [(CH3)3C–Si], 26.0 [(CH3)3C–Si], 59.6 (C-5), 71.8
(C-2), 118.4 (C-3), 128.6 (Cortho, -SO2Ph), 129.4 (Cmeta, -SO2Ph),
134.0 (Cpara, -SO2Ph), 138.6 (Cipso, -SO2Ph), 141.3 (C-4).
IR: 3200–3600, 3063, 2972, 2920, 1447, 1306, 1146, 1086, 972,
739, 689 cm–1.
(+)-(2S)-5-Benzenesulfonyl-1-iodo-2-(1-methoxy-1-methyl-
ethoxy)-pent-3-ene (17)
1H NMR (200 MHz, CDCl3): = 2.52 (1 H, d, J = 5.2 Hz, -OH),
3.08 (1 H, dd, J = 6.4, 10.2 Hz, HA-1), 3.20 (1 H, dd, J = 4.8, 10.2
Hz, HB-1), 3.81 (2 H, d, J = 7.4 Hz, H-5), 4.12 (1 H, m, H-2), 5.57
(1 H, dd, J = 5.0 , 15.4 Hz, H-3), 5.78 (1 H, m, H-4), 7.60 (3 H, m,
-SO2Ph), 7.87 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 13.3 (C-1), 59.6 (C-5), 70.9 (C-2),
119.2 (C-3), 128.7 (Cortho, -SO2Ph), 129.5 (Cmeta, -SO2Ph), 134.2
(Cpara, -SO2Ph), 138.4 (Cipso, -SO2Ph), 140.4 (C-4).
To a soln of 6 (0.16 g, 0.47 mmol) in 2-methoxypropene (2 mL) was
added a catalytic amount of pyridinium p-toluensulfonate. It was
left to stir for 1 h before addition of some drops of Et3N. The solvent
was then removed in vacuo and the resultant oil purified by column
chromatography (hexane–EtOAc, 9:1) to yield 0.20 g (100%) of 17.
[ ]D20 +4.6 (c 1.13, CHCl3).
IR: 2988, 2942, 1447, 1375, 1319, 1150, 1086, 1024, 972, 737, 689
cm–1.
MS: m/z (%) = 352 (2) [M+], 225 (18), 211 (65), 169 (100), 125 (35),
1H NMR (200 MHz, CDCl3): = 1.26, (3 H, s, Me2C), 1.33 (3 H, s,
Me2C), 2.98 (1 H, dd, J = 7.2, 9.8 Hz, HA-1), 3.11 (1 H, dd, J = 4.4,
9.8 Hz, HB-1), 3.16 (3 H, s, CH3O-), 3.83 (2 H, d, J = 6.6 Hz, H-5),
4.17 (1 H, m, H-2), 5.63 (2 H, m, H-3, H-4), 7.58 (3 H, m, -SO2Ph),
7.87 (2 H, m, -SO2Ph).
77 (60).
HRMS: m/z calcd for C11H13IO3S, 351.9630; found, 351.9631.
(+)-(2S)- 5-Benzenesulfonyl-1-iodo-2-(tetrahydropyran-2-
yloxy)-pent-3-ene (13)
13C NMR (50 MHz, CDCl3): = 10.7 (C-1), 25.4 (MeAC),
25.5 (MeBC), 49.8 (CH3O-), 59.7 (C-5), 69.9 (C-2), 101.6
[-OC(CH3)2(OCH3)], 119.0 (C-3), 128.6 (Cortho, -SO2Ph), 129.4
(Cmeta, -SO2Ph), 134.0 (Cpara, -SO2Ph), 138.7 (Cipso, -SO2Ph), 140.8
(C-4).
MS: m/z (%) = 425 (5) [M + 1+], 335 (7), 307 (15), 154 (100), 137
(58), 107 (25), 77 (30), 73 (25).
To a soln of 6 (0.12 g, 0.34 mmol) in CH2Cl2 (1 mL) was added di-
hydropyrane (80 L, 0.88 mmol) and a catalytic amount of p-tolue-
nesulfonic acid monohydrate. The reaction was left to stir for 19 h
before addition of Et2O. The soln was then poured into a separating
funnel, washed with a soln of NaHCO3 (5%), H2O, and sat. brine.
The organic phase was dried with anhyd Na2SO4, filtered and the
solvent removed in vacuo. The resultant oil was then purified by
flash silica column chromatography (hexane EtOAc, 9:1) to yield
0.09 g (69%) of 13 as a colorless oil. Some starting material was
also recovered from the column.
HRMS: m/z calcd for C15H22IO4S, 425.0284; found, 425.0284.
(+)-(2S)-5-Benzenesulfonyl-2(tetrahydropyran-2-yloxy)-1-
tosyloxy-pent-3-ene (10)
[ ]D20 +31.3 (c 1.04, CHCl3).
IR: 2944, 2868, 1447, 1319, 1150, 1086, 1020, 972, 743, 689 cm–1.
1H NMR (200 MHz, CDCl3): = 1.42–1.85 (6 H, m, H-2 , H-3 , H-
4 ), 3.10 (2 H, m, H-1), 3.51 (1 H, m, HA-5 ), 3.84 (2 H, d, J = 7.4
Hz, H-5), 3.96 (1 H, m, HB-5 ), 4.14 (1 H, m, H-2), 4.48 and 4.72 (1
H, m, H-1 ), 5.34–5.82 (2 H, m, H-3, H-4), 7.58 (3 H, m, -SO2Ph),
7.86 (2 H, m, -SO2Ph).
This experiment was carried out based on the procedure given for
obtaining compound 13 from 6. Compound 5 (0.19 g, 0.48 mmol),
CH2Cl2 (0.5 mL), dihydropyrane (0.13 mL, 1.42 mmol), and p-tol-
uenesulfonic acid monohydrate (cat.) were reacted for 16 h to yield
0.22 g (95%) of compound 10.
[ ]D20 +44.7 (c 0.94, CHCl3).
13C NMR (50 MHz, CDCl3): = 8.5 (C-1), 19.1 and 19.5 (C-3 ),
25.5 and 25.7 (C-4 ), 30.6 (C-2 ), 59.7 and 59.8 (C-5), 62.4 and 62.7
(C-5 ), 74.3 and 74.6 (C-2), 95.7 and 97.8 (C-1 ), 119.2 and 121.5
(C-3), 128.7 (Cortho, -SO2Ph), 129.4 (Cmeta, -SO2Ph), 134.0
(Cpara, -SO2Ph), 138.3 (Cipso, -SO2Ph), 138.7and 139.5 (C-4).
MS: m/z (%) = 436 (2) [M+], 335 (10), 295 (20), 208 (10), 141 (15),
85 (100), 67 (60).
IR: 2945, 2870, 1447, 1360, 1308, 1177, 1146, 976, 816 cm–1.
1H NMR (200 MHz, CDCl3): = 1.37–1.71 (6 H, m, H-2 , H-3 , H-
4 ), 2.45 (3 H, s, CH3-), 3.42 (1 H, m, HA-5 ), 3.65–4.00 (5 H, m, HB-
5 , H-5, H-1), 4.27 (1 H, m, H-2), 4.43 and 4.63 [1 H, m, H-1 (3:1)],
5.30–5.76 (2 H, m, H-3, H-4), 7.34 (2 H, m, Hmeta Ts-), 7.59 (3 H,
m, -SO2Ph), 7.80 (4 H, m, Hortho Ts-, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 18.8 and 19.4 (C-3 ), 21.9 (CH3-),
25.5 (C-4 ), 30.3 and 30.5 (C-2 ), 59.7 and 59.8 (C-5), 61.8 and 62.8
(C-5 ), 70.8 and 71.1 (C-1), 72.3 and 73.1 (C-2), 95.4 and 98.5
(C-1 ), 120.1 and 122.2 (C-3), 128.2 (Cortho, Ts-), 128.7 (Cortho
-SO2Ph), 129.3 (Cmeta, -SO2Ph), 130.1 (Cmeta, Ts-), 133.1 (Cipso
Ts-), 134.1 (Cpara, -SO2Ph), 135.7 and 136.6 (C-4), 138.3
(Cipso,-SO2Ph), 145.2 (Cpara, Ts-).
(–)-(2S)-5-Benzenesulfonyl-1-iodo-2-tert-butyldimethylsilyloxy-
pent-3-ene (16)
,
,
To a soln of 6 (0.14 g, 0.39 mmol) in THF (2 mL) was added 2,6
lutidine (0.14 mL, 1.17 mmol). The mixture was cooled to 0 °C.
Then tert-butyldimethylsilyl triflate (0.27 mL, 1.17 mmol) was add-
ed. The mixture was left to stir at r.t. for 30 min before addition of
sat. NaHCO3 soln, until neutralization. This soln was extracted with
Et2O and the organic extracts combined and washed with H2O,
NaHCO3 soln (5%) and sat. brine. The organic phase was dried with
anhyd Na2SO4, filtered and the solvent removed in vacuo. The re-
sultant oil was purified by column chromatography (hexane
EtOAc, 95:5) to yield 0.18 g (98%) of 16.
[ ]D20 –5.5 (c 1.38, CHCl3).
IR: 2928, 2855, 1464, 1321, 1258, 1152, 1088, 970, 837, 779 cm–1.
1H NMR (200 MHz, CDCl3): = 0.00 (3 H, s, MeA–Si), 0.07 (3 H,
s, MeB–Si), 0.87 [9 H, s, (CH3)3CSi], 3.01 (2 H, d, J = 5.8 Hz, H-1),
3.82 (2 H, d, J = 5.8 Hz, H-5), 4.15 (1 H, m, H-2), 5.63 (2 H, m, H-
3, H-4), 7.58 (3 H, m, -SO2Ph), 7.87 (2 H, m, -SO2Ph).
(+)-(2S)-5-Benzenesulfonyl-2-methoxymethoxy-1-tosyloxy-
pent-3-ene (11)
To a soln of 5 (0.10 g, 0.24 mmol) in CHCl3 (3 mL) was added
dimethoxymethane (0.65 mL, 7.24 mmol). The mixture was cooled
to 0 °C and P2O5 (0.47 g, 3.28 mmol) was added. The mixture was
left to stir at r.t. for 1 h before addition of ice. This soln was extract-
ed with Et2O and the organic extracts combined and washed with
NaHCO3 soln (5%), H2O (until pH 7) and sat. brine. The organic
phase was dried over anhyd Na2SO4, filtered and the solvent re-
moved in vacuo to yield 0.12 g of 11 (100%).
[ ]D20 +48.7 (c 1.05, CHCl3).
IR: 3067, 2963, 2924, 1597, 1447, 1358, 1096, 1020, 802, 665 cm–1.
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Cyclopropanols from Allylic Sulfones
57
1H NMR (200 MHz, CDCl3): = 2.41 (3 H, s, CH3C6H4SO2-), 3.23
(3 H, s, -OCH2OCH3), 3.75 (2 H, d, J = 7.4 Hz, H-1), 3.84 (2 H, d,
J = 5.2 Hz, H-5), 4.18 (1 H, m, H-2), 4.42 (2 H, s, -OCH2OCH3),
5.35 (1 H, dd, J = 6.6, 15.6 Hz, H-3), 5.69 (1 H, m, H-4), 7.31 (2 H,
d, J = 8.4 Hz, Hmeta Ts-), 7.54 (3 H, m, -SO2Ph), 7.76 (4 H, m,
Hortho Ts, -SO2Ph).
1H NMR (200 MHz, CDCl3): = 2.06 (1 H, m, -OH), 3.42 (2 H, m,
H-1), 3.80 (3 H, s, p-CH3OC6H4CH2-), 3.88 (3 H, m, H-2, H-5), 4.21
(1 H, d, J = 11.0 Hz, p-CH3OC6H4CHAHB-), 4.41 (1 H, d, J = 11.0
Hz, p-CH3OC6H4CHAHB-), 5.49 (1 H, dd, J = 7.0, 15.8 Hz, H-3),
5.76 (1 H, m, H-4), 6.87 (2 H, m, Hmeta p-CH3OC6H4CH2-), 7.18 (2
H, m, Hortho p-CH3OC6H4CH2-), 7.59 (3 H, m, -SO2Ph), 7.88 (2 H,
m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 55.5 (p-CH3OC6H4CH2-), 59.9
(C-5), 65.2 (C-1), 70.7 (p-CH3OC6H4CH2-), 79.3 (C-2), 114.2
(Cmeta, p-CH3OC6H4CH2-), 121.0 (C-3), 128.6 (Cortho, -SO2Ph),
129.4 (Cmeta, -SO2Ph), 129.8 (Cortho, p-CH3OC6H4CH2-), 129.9
(Cipso, p-CH3OC6H4CH2-), 134.2 (Cpara, -SO2Ph), 137.9 (C-4), 138.4
(Cipso, -SO2Ph), 159.6 (Cpara, p-CH3OC6H4CH2-).
13C NMR (50 MHz, CDCl3): = 21.8 (CH3C6H4SO2-), 55.8
(-OCH2OCH3), 59.6 (C-5), 70.9 (C-1), 73.1 (C-2), 94.5
(-OCH2OCH3), 122.0 (C-3), 128.1 (Cortho, Ts-), 128.6 (Cortho
-SO2Ph), 129.4 (Cmeta, -SO2Ph), 130.1 (Cmeta, Ts-), 132.9 (Cipso
,
,
Ts-), 134.2 (Cpara, -SO2Ph), 135.4 (C-4), 138.3 (Cipso, -SO2Ph),
145.3 (Cpara, Ts-).
(+)-(2S)-5-Benzenesulfonyl-[1,2]-(4-methoxybenzyliden)-pent-
3-ene-1,2-diol (7)
MS: m/z (%) = 362 (1) [M+], 300 (5), 210 (5), 154 (20), 67 (80).
To a soln of 4 (0.11 g, 0.47 mmol) in benzene (20 mL) was added
p-methoxybenzylidendimethylacetal (0.28 mL, 1.65 mmol) and a
catalytic amount of p-toluensulfonic acid monohydrate. The soln
was refluxed for 3 h using a Dean–Stark apparatus, and allowed to
cool. The soln was then poured into a separating funnel, washed
with a soln of NaHCO3 (5%), H2O and sat. brine. The organic phase
was dried with anhyd Na2SO4, filtered and the solvent removed in
vacuo. The resultant oil was purified by column chromatography
(hexane–EtOAc, 8:2) to yield 0.16 g (92%) of 7.
9
[ ]D20 –2.1 (c 1.33, CHCl3).
IR: 3200–3600, 3063, 2924, 2859, 1613, 1586, 1514, 1447, 1306,
1248, 1144, 1086, 1032, 974, 820, 739, 689 cm–1.
1H NMR (200 MHz, CDCl3): = 2.43 (1 H, m, -OH), 3.18 (1 H, dd,
J = 7.8, 9.6 Hz, HA-1), 3.37 (1 H, dd, J = 3.6, 9.6 Hz, HB-1), 3.78 (2
H, d, J = 7.2 Hz, H-5), 3.81 (3 H, s, p-CH3OC6H4CH2-), 4.26 (1 H,
m, H-2), 4.45 (2 H, s, p-CH3OC6H4CH2-), 5.52 (1 H, dd, J = 5.2,
15.4 Hz, H-3), 5.75 (1 H, m, H-4), 6.89 (2 H, m, Hmeta p-
CH3OC6H4CH2-), 7.23 (2 H, m, Hortho p-CH3OC6H4CH2-), 7.56 (3
H, m, -SO2Ph), 7.84 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 55.5 (p-CH3OC6H4CH2-), 59.9
(C-5), 70.5 (C-2), 73.3 (C-1, p-CH3OC6H4CH2-), 114.1 (Cmeta
p-CH3OC6H4CH2-), 118.5 (C-3), 128.8 (Cortho, -SO2Ph), 129.3
(Cmeta, -SO2Ph), 129.7 (Cortho, p-CH3OC6H4CH2-), 129.9 (Cipso
[ ]D20 +29.8 (c 1.61, CHCl3).
IR: 3065, 2924, 1615, 1518, 1447, 1308, 1250, 1148, 1084, 1030,
974, 831, 741 cm–1.
1H NMR (200 MHz, CDCl3): = 3.47 and 3.58 [1 H, dd, J = 7.4, 8.4
Hz, J = 5.8, 8.0 Hz, HA-1 (1:1)], 3.82 (5 H, m, p-CH3OC6H4-, H-5),
4.05 and 4.21 (1 H, dd, J = 7.4, 8.0 Hz, J = 6.6, 8.4 Hz, HB-1), 4.59
(1 H, m, H-2), 5.58 (1 H, m, H-3), 5.81 (2 H, m, H-4, p-
CH3OC6H4CH), 6.89 (2 H, m, Hmeta p-CH3OC6H4-), 7.35 (2 H, m,
,
,
p-CH3OC6H4CH2-), 134.0 (Cpara, -SO2Ph), 138.3 (Cipso, -SO2Ph),
139.1 (C-4), 159.8 (Cpara, p-CH3OC6H4CH2-).
Hortho p-CH3OC6H4-), 7.57 (3 H, m, -SO2Ph), 7.90 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 55.6 (p-CH3OC6H4-), 59.7 (C-5),
70.0 and 70.3 (C-1), 75.9 and 76.5 (C-2), 104.1 and 104.7 (p-
CH3OC6H4CH), 114.0 (Cmeta, p-CH3OC6H4-), 119.7 and 120.0 (C-
3), 128.0 and 128.2 (Cortho, p-CH3OC6H4-), 128.8 (Cortho, -SO2Ph),
(+)-(2S)-5-Benzenesulfonyl-2-(4-methoxybenzyloxy)-1-
tosyloxy-pent-3-ene (12)
This experiment was carried out based on the procedure given for
obtaining compound 5 from 4. Compound 8 (29 mg, 0.08 mmol),
pyridine (1 mL), and TsCl (45 mg, 0.24 mmol) were reacted for 2 d
and 16 h to yield 35 mg (86%) of compound 12.
129.4 (Cmeta, -SO2Ph), 129.9 (Cipso, p-CH3OC6H4), 134.1 (Cpara
,
-SO2Ph), 138.0 and 138.3 (C-4), 138.3 (Cipso, -SO2Ph), 160.7 (Cpara
,
p-CH3OC6H4-).
MS: m/z (%) = 361 (1) [M + 1+], 307 (12), 154 (100), 67 (80).
[ ]D20 +22.4 (c 1.62, CHCl3).
IR: 3065, 2959, 2872, 1613, 1514, 1447, 1362, 1308, 1250, 1177,
1146, 1080, 1032, 978, 818, 665 cm–1.
HRMS: m/z calcd for C19H21O5S, 361.1110; found, 361.1110.
1H NMR (200 MHz, CDCl3): = 2.43 (3 H, s, CH3C6H4SO2-), 3.80
(3 H, s, p-CH3OC6H4CH2-), 3.80 (2 H, d, J = 7.4 Hz, H-5),
3.86 (2 H, m, H-1), 3.95 (1 H, m, H-2), 4.20 (1 H, d,
J = 11.4 Hz, p-CH3OC6H4CHAHB-), 4.35 (1 H, d,
J = 11.4 Hz, p-CH3OC6H4CHAHB-), 5.41 (1 H, dd, J = 6.2,
15.4 Hz, H-3), 5.73 (1 H, m, H-4), 6.84 (2 H, m, Hmeta
p-CH3OC6H4CH2-), 7.12 (2 H, m, Hortho p-CH3OC6H4CH2-), 7.29 (2
H, d, J = 8.2 Hz, Hmeta Ts-), 7.58 (3 H, m, -SO2Ph), 7.73 (2 H, d,
J = 8.0 Hz, Hortho Ts-), 7.84 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 21.9 (CH3C6H4SO2-), 55.5 (p-
CH3OC6H4CH2-), 59.7 (C-5) 70.9 (C-1), 71.0 (p-CH3OC6H4CH2-),
75.8 (C-2), 114.0 (Cmeta, p-CH3OC6H4CH2-), 122.0 (C-3), 128.2
(Cortho, Ts-), 128.6 (Cortho, -SO2Ph), 129.5 (Cmeta, -SO2Ph), 129.6
(+)-(2S)-5-Benzenesulfonyl-2-(4-methoxybenzyloxy)-pent-3-en-
1-ol (8)
(–)-(2S)-5-Benzenesulfonyl-1-(4-methoxybenzyloxy)-pent-3-en-
2-ol (9)
A soln of trimethylsilyl chloride (0.44 mL, 3.44 mmol) in CH3CN
(0.5 mL) was added dropwise to a stirred mixture containing com-
pound 7 (0.16 g, 0.43 mmol), sodium cyanoborohydride (0.33 g,
5.20 mmol) in CH3CN (8.5 mL). The reaction mixture was stirred
for 1 h at r.t. The mixture was filtered through celite and poured into
ice-cold sat. aq NaHCO3. The aq phase was repeatedly extracted
with CH2Cl2. The combined extracts were washed with sat. aq
NaHCO3, dried (Na2SO4), filtered and concentrated. The residue
was purified by flash silica column chromatography (hexane–
EtOAc, 7:3) to yield 0.10 g (70%) of compounds 8 and 9 (1:1).
(Cortho, Cipso, p-CH3OC6H4CH2-), 130.1 (Cmeta, Ts-), 133.0 (Cipso
,
Ts-), 134.2 (Cpara, -SO2Ph), 136.2 (C-4), 138.4 (Cipso, -SO2Ph),
145.2 (Cpara, p-CH3OC6H4CH2-).
MS: m/z (%) = 517 (3) [M +1+], 307 (10), 239 (5), 136 (80), 154
8
[ ]D20 +54.7 (c 1.26, CHCl3).
(40), 121 (100).
IR: 3200–3600, 2924, 2870, 1613, 1514, 1447, 1306, 1248, 1144,
1086, 1032, 976, 741, 689 cm–1.
HRMS: m/z calcd for C26H29O7S2, 517.1355; found, 517.1355.
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York

58
D. Díez et al.
PAPER
(+)-(2S)-5-Benzenesulfonyl-1-iodo-2-(tetrahydropyran-2-
yloxy)-pent-3-ene (13)
were obtained in a 70:30 ratio separated by flash silica column chro-
matography (hexane–EtOAc, 9:1).
This experiment was carried out based on the procedure given for
obtaining compound 6 from 5. Compound 10 (0.22 g, 0.46 mmol),
acetone (5 mL), and sodium iodide (0.28 g, 1.84 mmol) were react-
ed for 14 h to yield 0.15 g (76%) of compound 13.
(+)-(1R,2S)-2-[2-(2-Benzenesulfonylvinyl)-1-(tetrahydropyran-
2-yloxy)]-cyclopropane (18)
[ ]D20 +17.2 (c 0.79, CHCl3).
IR: 3063, 2942, 2853, 1620, 1447, 1308, 1146, 1086, 1036, 974,
802 cm–1.
(+)-(2S)-5-Benzenesulfonyl-1-iodo-2-methoxymethoxy-pent-3-
ene (14)
This experiment was carried out based on the procedure given for
obtaining compound 6 from 5. Compound 11 (0.10 g, 0.24 mmol),
acetone (3 mL), and sodium iodide (0.18 g, 1.20 mmol) were react-
ed for 20 h to yield 0.08 g (84%) of compound 14.
[ ]D20 +44.7 (c 0.90, CHCl3).
IR: 2955, 2892, 1447, 1308, 1146, 1086, 1024, 974, 741, 689 cm–1.
1H NMR (200 MHz, CDCl3): = 3.09 (2 H, d, J = 6.0 Hz, H-1), 3.38
(3 H, s, -OCH2OCH3), 3.83 (2 H, d, J = 7.2 Hz, H-5), 4.05 (1 H, m,
H-2), 4.53 (2 H, s, -OCH2OCH3), 5.45 (1 H, dd, J = 7.0, 15.4, H-3),
5.73 (1 H, m, H-4), 7.60 (3 H, m, -SO2Ph), 7.87 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 8.2 (C-1), 56,3 (-OCH2OCH3),
59.7 (C-5), 75.0 (C-2), 94.5 (-OCH2OCH3), 121.3 (C-3), 128.6
(Cortho, -SO2Ph), 129.5 (Cmeta, -SO2Ph), 134.1 (Cpara, -SO2Ph), 138.4
(Cipso, -SO2Ph), 138.7 (C-4).
1H NMR (200 MHz, CDCl3): = 0.93 and 1.04 [1 H, q, J = 6.2 Hz,
H -3 (3:7)], 1.24 and 1.43 (1 H, ddd, J = 4.0, 6.2, 9.8 Hz, H -3),
1.42–1.80 (6.3 H, m, H-2 , H-3 , H-4 , 0.3 H-2), 1.87 (0.7 H, dddd,
J = 2.2, 6.2, 9.6, 9.6 Hz, 0.7 H-2), 3.56 (1.3 H, HA-5 , 0.3 H-1), 3.71
(0.7 H, ddd, J = 2.2, 4.0, 6.6 Hz, 0.7 H-1), 3.88 (1 H, m, HB-5 ), 4.68
(1 H, m, H-1 ), 6.28 and 6.25 (1 H, d, J = 15.0 Hz, -CH=CHSO2Ph),
6.54 (1 H, dd, J = 9.6, 15.0 Hz, -CH=CH–SO2Ph), 7.56 (3 H, m, -
SO2Ph), 7.86 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 16.0 and 17.1 (C-3), 19.3 and 19.4
(C-3 ), 21.5 and 22.2 (C-2), 25.5 (C-4 ), 30.6 (C-2 ), 59.0 (C-1), 62.6
and 62.8 (C-5 ), 99.1 (C-1 ), 127.5 and 128.2 (-CH=CH-SO2Ph),
127.7 (Cortho, -SO2Ph), 129.5 (Cmeta, -SO2Ph), 133.4 (Cpara, -SO2Ph),
141.1 (Cipso, -SO2Ph), 147.9 and 148.0 (-CH=CHSO2Ph).
MS: m/z (%) = 309 (2) [M+], 279 (5), 167 (8), 149 (15), 125 (10), 85
(100).
HRMS: m/z calcd for C16H20O4S, 308.1082; found, 308.1083.
(+)-(2S)-5-Benzenesulfonyl-1-iodo-2-(4-methoxybenzyloxy)-
pent-3-ene (15)
This experiment was carried out based on the procedure given for
obtaining compound 6 from 5. Compound 12 (47 mg, 0.24 mmol),
acetone (5 mL), and sodium iodide (54 mg, 0.36 mmol) were react-
ed for 3 d and 13 h to yield 44 mg (100%) of compound 15.
(–)-(1R,2R)-2-[2-(2-Benzenesulfonylvinyl)-1-(tetrahydropyran-
2-yloxy)]-cyclopropane (19)
[ ]D20 –41.7 (c 0.87, CHCl3).
IR: 3063, 2945, 2870, 1618, 1447, 1317, 1144, 1086, 1038, 999,
754, 689 cm–1.
[ ]D20 +28.3 (c 1.01, CHCl3).
1H NMR (200 MHz, CDCl3): = 0.91 (1 H, m, H -3), 1.12–1.81 (8
H, m, H-2 , H-3 , H-4 , H-2, H -3), 3.52 (1 H, m, HA-5 ), 3.75–4.01
(2 H, m, HB-5 , H-1), 4.42 and 4.72 (1 H, m, H-1 ), 6.37 (1 H, m,
-CH=CHSO2Ph), 6.80 (1 H, m, -CH=CHSO2Ph), 7.53 (3 H, m,
-SO2Ph), 7.87 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 15.8 and 16.9 (C-3), 19.3 and 19.5
(C-3 ), 20.5 and 21.1 (C-2), 25.6 (C-4 ), 30.3 and 30.6 (C-2 ), 57.0
IR: 2959, 2924, 2853, 1613, 1586, 1514, 1447, 1308, 1248, 1175,
1148, 1086, 1032, 972, 822, 741, 689 cm–1.
1H NMR (200 MHz, CDCl3): = 3.06 (2 H, d, J = 5.8 Hz, H-1), 3.81
(3 H, s, p-CH3OC6H4CH2-), 3.81 (1 H, m, H-2), 3.86 (2 H, d, J = 7.4
Hz, H-5), 4.27 (1 H, d, J = 11.4 Hz, p-CH3OC6H4CHAHB-), 4.40 (1
H, d, J = 11.4 Hz, p-CH3OC6H4CHAHB-), 5.49 (1 H, dd, J = 6.8,
15.4 Hz, H-3), 5.74 (1 H, m, H-4), 6.87 (2 H, m, Hmeta p-
CH3OC6H4CH2-), 7.23 (2 H, m, Hortho p-CH3OC6H4CH2-), 7.59 (3
H, m, -SO2Ph) 7.88 (2 H, m, -SO2Ph).
(C-1), 62.6 and 62.8 (C-5 ), 99.3 (C-1 ), 127.6 and 127.7 (Cortho
-SO2Ph), 128.5 and 128.6 (-CH=CHSO2Ph), 129.3 and 129.4 (Cmeta
-SO2Ph), 133.2 (Cpara, -SO2Ph), 141.4 (Cipso, -SO2Ph), 146.8 and
,
,
13C NMR (50 MHz, CDCl3): = 8.2 (C-1), 55.5 (p-CH3OC6H4-
CH2-), 59.7 (C-5), 70.8 (p-CH3OC6H4CH2-), 77.6 (C-2), 114.1 (Cme-
ta, p-CH3OC6H4CH2-), 121.1 (C-3), 128.6 (Cortho, -SO2Ph), 129.5
(Cmeta, -SO2Ph), 129.7 (Cipso, p-CH3OC6H4CH2-), 129.8 (Cortho, p-
CH3OC6H4CH2-), 134.2 (Cpara, -SO2Ph), 138.5 (Cipso, -SO2Ph),
139.2 (C-4), 159.6 (Cpara, p-CH3OC6H4CH2-).
147.4 (-CH=CH–SO2Ph).
MS: m/z (%) = 308 (2) [M+], 224 (5), 195 (8), 125 (15), 85 (100).
HRMS: m/z calcd for C16H20O4S, 308.1082; found, 308.1087.
Reaction of compound 14 with LDA
This experiment was carried out based on the procedure given for
the above reaction. BuLi, 1.6 M (0.19 mL, 0.30 mmol), diisopropy-
lamine (42 L, 0.30 mmol), THF (0.5 mL), compound 14 (79 mg,
0.20 mmol) in THF (1 mL) were reacted for 90 min to yield 49 mg
(91%) of cyclopropanes 20 and 21 in a 70:30 ratio, and separated by
column chromatography (hexane–EtOAc, 8:2).
MS: m/z (%) = 472 (1) [M+], 300 (5), 295 (5), 208 (5), 154 (40), 85
(70), 67 (100).
LDA Reaction; General Procedure
Reaction of compound 13 with LDA
LDA was generated by the addition of BuLi 1.6 M (0.17 mL, 0.27
mmol) to a soln of diisopropylamine (38 L, 0.27 mmol) in THF
(0.5 mL) at –78 °C. After 5 min, the mixture was allowed to warm
to r.t., and then recooled to –78 °C.
(–)-(1R,2S)-2-(2-Benzenesulfonylvinyl)-1-methoxymethoxy-
cyclopropane (20)
[ ]D20 –16.0 (c 0.83, CHCl3).
IR: 3057, 2922, 2851, 1622, 1447, 1306, 1144, 1086, 1051, 999,
799 cm–1.
Compound 13 (80 mg, 0.18 mmol) was then added to the reaction
flask via cannula as a soln in THF (1 mL). The reaction mixture was
left to stir for 1 h at –78 °C under Argon before the addition of sat.
ammonium chloride soln (1 mL). The product was extracted into
EtOAc (3 ). The organic extracts were combined, washed with
H2O and sat. brine, then dried over anhyd Na2SO4, filtered and re-
moved the solvent in vacuo. Cyclopropanes 18 and 19, 53 mg (94%)
1H NMR (200 MHz, CDCl3): = 1.00 (1 H, q, J = 6.2 Hz, H -3),
1.33 (1 H, ddd, J = 4.0, 6.2, 9.8 Hz, H -3), 1.76 (1 H, dddd, J = 2.2,
6.2, 9.6, 9.6 Hz, H-2), 3.38, (3 H, s, -OCH2OCH3), 3.61 (1 H, ddd,
J = 2.2, 4.0, 6.2 Hz, H-1), 4.62 (2 H, s, -OCH2OCH3), 6.28 (1 H, d,
J = 14.6 Hz, -CH=CH–SO2Ph), 6.53 (1 H, dd, J = 9.4, 14.6 Hz,
-CH=CHSO2Ph), 7.57 (3 H, m, -SO2Ph), 7.86 (2 H, m, -SO2Ph).
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Cyclopropanols from Allylic Sulfones
59
13C NMR (50 MHz, CDCl3): = 16.5 (C-3), 21.8 (C-2), 56.2
1H NMR (200 MHz, CDCl3): = 1.12 (1 H, dt, J = 4.0, 6.2, 6.2 Hz,
H -3), 1.22 (1 H, m, H -3), 1.62 (1 H, m, H-2), 3.65 (1 H, dt, J = 4.0,
6.2, 6.2 Hz, H-1), 3.81 (3 H, s, p-CH3OC6H4CH2-), 4.38 (2 H, s, p-
CH3OC6H4CH2-), 6.43 (1 H, d, J = 15.2Hz, -CH=CHSO2Ph), 6.89
(3 H, m, -CH=CHSO2Ph), Hmeta p-CH3OC6H4CH2-), 7.24 (2 H, m,
Hortho p-CH3OC6H4CH2-), 7.54 (3 H, m, -SO2Ph), 7.87 (2 H, m, -
SO2Ph).
13C NMR (50 MHz, CDCl3): = 16.8 (C-3), 21.0 (C-2), 55.5 (p-
CH3OC6H4CH2-), 59.7 (C-1), 73.4 (p-CH3OC6H4CH2-), 114.2
(Cmeta, p-CH3OC6H4CH2-), 127.7 (Cortho, -SO2Ph), 128.6
(-OCH2OCH3), 59.1 (C-1), 96.8 (-OCH2OCH3), 127.7 (Cortho
,
-SO2Ph), 128.1 (-CH=CHSO2Ph), 129.5 (Cmeta, -SO2Ph), 133.4
(Cpara, -SO2Ph), 141.0 (Cipso, -SO2Ph), 147.5 (-CH=CHSO2Ph).
MS: m/z (%) = 269 (1) [M + 1+] 149 (10), 135 (10), 91 (100).
(+)-(1R,2R)-2-(2-Benzenesulfonylvinyl)-1-methoxymethoxy-
cyclopropane (21)
[ ]D20 +6.8 (c 1.04, CHCl3).
IR: 3054, 2926, 2853, 1622, 1447, 1306, 1283, 1142, 1086, 1032,
993, 797 cm–1.
(-CH=CHSO2Ph), 129.2 (Cipso, p-CH3OC6H4CH2-), 129.4 (Cmeta
,
-SO2Ph), 130.0 (Cortho, p-CH3OC6H4CH2-), 133.2 (Cpara, -SO2Ph),
141.4 (Cipso, -SO2Ph), 146.9 (-CH=CH–SO2Ph), 159.8 (Cpara, p-
CH3OC6H4CH2-).
MS: m/z (%) = 345 (2) [M + 1+], 307 (5), 154 (26), 136 (25).
HRMS: m/z calcd for C19H21O4S, 345.1161; found, 345.1166.
Reaction of compound 16 with LDA
1H NMR (200 MHz, CDCl3): = 1.07 (1 H, dt, J = 4.4, 6.2, 6.2 Hz,
H -3), 1.25 (1 H, m, H -3), 1.64 (1 H, m, H-2), 3.40 (3 H, s, -
OCH2OCH3), 3.83 (1 H, dt, J = 4.4, 6.2, 6.2 Hz, H-1), 4.55 (1 H, d,
J = 6.6 Hz, -OCHAHBOCH3), 4.63 (1 H, d, J = 6.6 Hz, -
OCHAHBOCH3), 6.41 (1 H, d, J = 15.0, -CH=CHSO2Ph), 6.80 (1 H,
dd, J = 10.2, 15.0 Hz, -CH=CHSO2Ph), 7.54 (3 H, m, -SO2Ph), 7.88
(2 H, m, -SO2Ph).
This experiment was carried out based on the procedure given for
the above reaction. BuLi 1.6 M (0.36 mL, 0.58 mmol), diisopropy-
lamine (81 L, 0.58 mmol), THF (1 mL), compound 16 (0.18 g,
0.38 mmol) in THF (1 mLwere reacted for 45 min to yield 0.12 g
(91%) of cyclopropanes 24 and 25 in a 30:70 ratio and separated by
flash silica column chromatography (hexane–EtOAc, 9:1).
13C NMR (50 MHz, CDCl3): = 16.2 (C-3), 20.6 (C-2), 56.4
(-OCH2OCH3), 57.3 (C-1), 97.0 (-OCH2OCH3), 127.7 (Cortho
,
-SO2Ph), 128.9 (-CH=CHSO2Ph), 129.4 (Cmeta, -SO2Ph), 133.3
(Cpara, -SO2Ph), 141.3 (Cipso, -SO2Ph), 146.6 (-CH=CHSO2Ph).
MS: m/z (%) = 269 (1) [M + 1+] 136 (20), 114 (10), 77 (100).
Reaction of compound 15 with LDA
(–)-(1R,2S)-2-(2-Benzenesulfonylvinyl)-1-tert-butyldimethyl-
sililoxy-cyclopropane (24)
This experiment was carried out based on the procedure given for
the above reaction. BuLi 1.6 M (80 ml, 0.13 mmol), diisopropy-
lamine (18 L, 0.13 mmol), THF (0.5 mL), compound 15 (41 mg,
0.08 mmol) in THF (1 mL) were reacted for 1 h to yield 20 mg
(68%) of cyclopropanes 22 and 23 in a 50:50 ratio and separated by
flash silica column chromatography (hexane–EtOAc, 9:1).
[ ]D20 –64.4 (c 0.50, CHCl3).
IR: 3065, 2957, 2930, 2857, 1622, 1447, 1317, 1209, 1148, 1086,
916, 837, 801 cm–1.
1H NMR (200 MHz, CDCl3): = 0.08 (6 H, s, MeASi, MeBSi), 0.86
[9 H, s, (CH3)3CSi], 0.96 (1 H, q, J = 6.2 Hz, H -3), 1.25 (1 H, ddd,
J = 4.0, 6.2, 9.6 Hz, H -3), 1.64 (1 H, dddd, J = 2.2, 6.4, 9.4, 9.4 Hz,
H-2), 3.49 (1 H, ddd, J = 2.2, 4.0, 6.2 Hz, H-1), 6.23 (1 H, d,
J = 15.0 Hz, -CH=CHSO2Ph), 6.53 (1 H, dd, J = 9.4, 15.0 Hz,
-CH=CHSO2Ph), 7.54 (3 H, m, -SO2Ph), 7.85 (2 H, m, -SO2Ph).
(–)-(1R,2S)-2-(2-Benzenesulfonylvinyl)-1-(4-methoxybenzyl-
oxy)-cyclopropane (22)
[ ]D20 –26.2 (c 0.98, CHCl3).
IR: 3054, 2922, 2851, 1615, 1514, 1447, 1306, 1248, 1146, 1086,
1034, 802, 752, 689 cm–1.
13C NMR (50 MHz, CDCl3): = –4.8 (MeASi), –4.7 (MeBSi), 18.2
[(CH3)3C–Si], 18.7 (C-3), 23.7 (C-2), 25.9 [(CH3)3CSi], 56.9 (C-1),
1H NMR (200 MHz, CDCl3): = 0.97 (1 H, q, J = 6.2 Hz, H -3),
1.35 (1 H, ddd, J = 4.0, 6.2, 10.0 Hz, H -3), 1.66 (1 H, dddd, J = 2.2,
6.2, 10.0, 10.0 Hz, H-2), 3.39 (1 H, ddd, J = 2.2, 4.2, 6.2 Hz, H-1),
3.79 (3 H, s, p-CH3OC6H4CH2-), 4.47 (1 H, br s, p-
CH3OC6H4CHAHB-), 4.48 (1 H, s, p-CH3OC6H4CHAHB-), 6.18 (1
H, d, J = 15.0 Hz, -CH=CH–SO2Ph), 6.48 (1 H, dd, J = 10.0, 15.2
Hz, -CH=CHSO2Ph), 6.84 (2 H, m, Hmeta p-CH3OC6H4CH2-), 7.20
(2 H, m, Hortho p-CH3OC6H4CH2-), 7.56 (3 H, m, -SO2Ph), 7.86 (2
H, m, -SO2Ph).
127.3 (-CH=CH–SO2Ph), 127.6 (Cortho, -SO2Ph), 129.4 (Cmeta
,
-SO2Ph), 133.3 (Cpara, -SO2Ph), 141.3 (Cipso, -SO2Ph), 148.5
(-CH=CHSO2Ph).
MS: m/z (%) = 339 (5) [M+], 281 (20), 197 (15), 135 (10), 73 (100).
HRMS: m/z calcd for C17H27O3SSi, 339.1450; found, 339.1450.
(–)-(1R,2R)-2-(2-Benzenesulfonylvinyl)-1-tert-butyldimethyl-
sililoxy-cyclopropane (25)
13C NMR (50 MHz, CDCl3): = 16.9 (C-3), 22.4 (C-2), 55.5
[ ]D20 –59.5 (c 0.56, CHCl3).
(p-CH3OC6H4CH2-), 61.6 (C-1), 73.2 (p-CH3OC6H4CH2-), 114.1
IR: 2957, 2930, 2857, 1624, 1447, 1317, 1260, 1146, 1086, 1020,
837, 793, 667 cm–1.
(Cmeta, p-CH3OC6H4CH2-), 127.7 (-CH=CH–SO2Ph, Cortho
,
-SO2Ph), 129.3 (Cipso, p-CH3OC6H4CH2-), 129.5 (Cmeta, -SO2Ph),
130.1 (Cortho, p-CH3OC6H4CH2-), 133.4 (Cpara, -SO2Ph), 141.2
(Cipso, -SO2Ph), 147.9 (-CH=CH–SO2Ph), 159.8 (Cpara, p-CH3
OC6H4CH2-).
MS: m/z (%) = 345 (5) [M + 1+], 307 (14), 154 (85), 125 (25), 107
(50).
1H NMR (200 MHz, CDCl3): = 0.05 (3 H, s, MeASi), 0.08 (3 H, s,
MeBSi), 0.88 [9 H, s, (CH3)3CSi], 0.94 (1 H, dt, J = 4.0, 5.8, 5.8 Hz,
H -3), 1.18 (1 H, dt, J = 9.6, 5.8, 5.8 Hz, H -3), 1.54 (1 H, m, H-2),
3.75 (1 H, dt, J = 4.2, 5.8, 5.8 Hz, H-1), 6.37 (1 H, d, J = 15.0 Hz,
-CH=CHSO2Ph), 6.83 (1 H, dd, J = 9.8, 15.0 Hz, -CH=CHSO2Ph),
7.52 (3 H, m, -SO2Ph), 7.88 (2 H, m, -SO2Ph).
HRMS: m/z calcd for C19H21O4S, 345.1161; found, 345.1161.
13C NMR (50 MHz, CDCl3): = –5.0 (MeASi), –4.9 (MeBSi), 18.3
[(CH3)3CSi, C-3], 21.0 (C-2), 25.9 [(CH3)3C–Si], 54.4 (C-1), 127.7
(+)-(1R,2R)-2-(2-Benzenesulfonylvinyl)-1-(4-methoxybenzyl-
oxy)-cyclopropane (23)
(Cortho, -SO2Ph), 128.5 (-CH=CHSO2Ph), 129.3 (Cmeta
,
-SO2Ph), 133.2 (Cpara, -SO2Ph), 141.5 (Cipso, -SO2Ph),
147.8 (-CH=CHSO2Ph).
[ ]D20 +8.7 (c 0.91, CHCl3).
IR: 3057, 2926, 2855, 1615, 1514, 1447, 1306, 1250, 1144, 1086,
1032, 799, 754, 689 cm–1.
MS: m/z (%) = 339 (5) [M+], 281 (23), 197 (20), 136 (20), 73 (100).
HRMS: m/z calcd for C17H27O3SSi, 339.1450; found, 339.1450.
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York

60
D. Díez et al.
PAPER
Reaction of compound 17 with LDA
by column chromatography (hexane–EtOAc, 8:2) to yield 14 mg
(100%) of 29.
[ ]D20 +39.4 (c 0.69, CHCl3).
This experiment was carried out based on the procedure given for
the above reaction. BuLi 1.6 M (0.12 mL, 0.19 mmol), diisopro-
pylamine (26 L, 0.19 mmol), THF (0.5 mL) compound 17 (53 mg,
0.13 mmol) in THF (1 mL) were reacted for 90 min to yield 43 mg
(100%) of cyclopropanes 26 and 27 in a 40:60 ratio and separated
by flash silica column chromatography (hexane–EtOAc, 9:1).
IR: 3063, 2942, 2870, 1447, 1306, 1148, 1086, 1038, 993, 735, 691
cm–1.
1H NMR (200 MHz, CDCl3): = 0.32 and 0.46 (1 H, q and m,
J = 5.8 Hz, H -3), 0.71 and 0.92 (1 H, ddd, J = 3.4, 5.8, 9.2 Hz, H -
3), 0.92 (1 H, m, H-2), 1.41–1.82 (8 H, m, H-2 , H-3 , H-4 ,
-CH2CH2SO2Ph), 3.21 (3 H, m, H-1, -CH2CH2SO2Ph), 3.55 (1 H,
m, HA-5 ), 3.87 (1 H, m, HB-5 ), 4.62 (1 H, m, H-1 ), 7.62 (3 H, m,
-SO2Ph), 7.92 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 11.8 and 13.5 (C-3), 16.8 and 18.0
(C-2), 19.3 and 19.6 (C-3 ), 25.3 (-CH2CH2SO2Ph), 25.5 (C-4 ),
30.5 (C-2 ), 55.7 (-CH2CH2-SO2Ph), 55.8 and 56.2 (C-1), 62.4 and
62.8 (C-5 ), 98.8 and 99.1 (C-1 ), 128.2 (Cortho, -SO2Ph), 129.4
(Cmeta, -SO2Ph), 133.8 (Cpara, -SO2Ph), 139.3 (Cipso, -SO2Ph).
(–)-(1R,2S)-2-(2-Benzenesulfonylvinyl)-1-(1-Methoxy-1-meth-
ylethoxy)-cyclopropane (26)
[ ]D20 –7.5 (c 1.41, CHCl3).
IR: 3059, 2992, 2944, 1624, 1447, 1373, 1308, 1283, 1211, 1146,
1086, 1067, 802 cm–1.
1H NMR (200 MHz, CDCl3): = 0.98 (1 H, q, J = 6.2 Hz, H -3),
1.30 (1 H, m, H -3), 1.32 (3 H, s, MeAC), 1.33 (3 H, s, MeBC), 1.65
(1 H, dddd, J = 2.2, 6.2, 9.6, 9.6 Hz, H-2), 3.21 (1 H, s, CH3O-), 3.44
(1 H, ddd, 2.2, 4.4, 6.2 Hz, H-1), 6.25 (1 H, d, J = 15.0 Hz,
-CH=CH–SO2Ph), 6. 53 (1 H, dd, J = 9. 4, 15. 0 Hz,
-CH=CHSO2Ph), 7.53 (3 H, m, -SO2Ph), 7.85 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 16.0 (C-3), 22.4 (C-2), 24.6
(MeAC), 25.3 (MeBC), 49.0 (CH3O-), 54.4 (C-1), 102.0 [-
OC(CH3)2(OCH3)], 127.6 (Cortho, -SO2Ph), 127.7 (-CH=CHSO2Ph),
129.4 (Cmeta, -SO2Ph), 133.4 (Cpara, -SO2Ph), 141.2 (Cipso, -SO2Ph),
148.1 (-CH=CHSO2Ph).
(–)-(1R,2R)-2-(2-Benzenesulfonylethyl)-1-(tetrahydropyran-2-
yloxy)-cyclopropane (34)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Compound 19 (6 mg, 0.02 mmol) was
reacted for 15 h to yield 5 mg (90%) of hydrogenated product 34.
[ ]D20 –31.7 (c 0.52, CHCl3).
IR: 3071, 2940, 2868, 1447, 1306, 1148, 1088, 1036, 741, 691 cm–1.
1H NMR (400 MHz, CDCl3): = 0.13 and 0.33 (1 H, dt, J = 3.2, 6.0,
6.0 Hz, H -3), 0.62 and 0.73 (1 H, dt and m, J = 9.2, 6.0, 6.0 Hz, H -
3), 0.87 (1 H, m, H-2), 130 and 2.07 (8 H, m, H-2 , H-3 , H-4 ,
-CH2CH2SO2Ph), 3.21 (2 H, m, -CH2CH2SO2Ph), 3.34 and 3.52 (1
H, ddd and m, J = 5.2, 10.8, 14.0 Hz, H-1), 3.52 (1 H, m, HA-5 ),
3.84 (1 H, m, HB-5 ), 4.55 and 4.60 (1 H, m, H-1 ), 7.56 (2 H, m,
-SO2Ph), 7.64 (1 H, m, -SO2Ph), 7.92 (2 H, m, -SO2Ph).
13C NMR (100 MHz, CDCl3): = 10.9 and 11.2 (C-3), 14.7 and 15.5
(C-2), 19.1 and 19.5 (C-3 ), 20.9 and 21.7 (-CH2CH2SO2Ph), 25.1
and 25.3 (C-4 ), 30.3 and 30.4 (C-2 ), 52.9 and 53.7 (C-1), 55.9 and
56.4 (-CH2CH2SO2Ph), 62.2 and 62.5 (C-5 ), 98.9 and 99.3 (C-1 ),
128.0 (Cortho, -SO2Ph) 129.1 (Cmeta, -SO2Ph), 133.4 (Cpara, -SO2Ph),
139.3 (Cipso, -SO2Ph).
(+)-(1R,2R)-2-(2-Benzenesulfonylvinyl)-1-(1-Methoxy-1-meth-
ylethoxy)-cyclopropane (27)
[ ]D20 +59.1 (c 1.16, CHCl3).
IR: 3057, 2994, 2944, 1622, 1447, 1373, 1306, 1209, 1144, 1086,
1067, 1005, 820, 799, 752, 689 cm–1.
1H NMR (200 MHz, CDCl3): = 0.99 (1 H, dt, J = 4.4, 6.2, 6.2 Hz,
H -3), 1.25 (3 H, s, MeAC), 1.28 (1 H, m, H -3), 1.31 (3 H, s, Me-
BC), 1.58 (1 H, m, H-2), 3.22 (3 H, s, CH3O-), 3.72 (1 H, dt, J = 4.4,
6.2, 6.2 Hz, H-1), 6.36 (1 H, d, J = 15.0 Hz, -CH=CHSO2Ph), 6.80
(1 H, dd, J = 10.4, 15.0 Hz, -CH=CHSO2Ph), 7.53 (3 H, m,
-SO2Ph), 7.87 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 15.8 (C-3), 20.5 (C-2),
24.4 (MeAC), 25.1 (MeBC), 49.0 (CH3O-), 52.5 (C-1),
101.8 [(-OC(CH3)2(OCH3)], 127.6 (Cortho, -SO2Ph), 128.3
(-CH=CHSO2Ph), 129.4 (Cmeta, -SO2Ph), 133.2 (Cpara, -SO2Ph),
141.5 (Cipso, -SO2Ph), 147.8 (-CH=CHSO2Ph).
(–)-(1R,2S)-2-(2-Benzenesulfonylethyl)-1-methoxymethoxy-
cyclopropane (31)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Compound 20 (16 mg, 0.06 mmol) was
reacted for 15 h to yield 14 mg (89%) of the hydrogenated product
31.
5-Benzenesulfonyl-pent-2-enal (28)
Cyclopropane 18 (13 mg, 0.04 mmol) was dissolved in AcOH–
THF–H2O, 4:1:1 (2 mL). It was left for 12 h before pouring into an
Erlenmeyer with a buffer soln (pH = 7.2). The aq layer was extract-
ed with EtOAc, and the organic layer dried over anhyd Na2SO4, fil-
tered and the solvent removed in vacuo. The resultant oil was
purified by flash silica column chromatography (hexane–EtOAc,
85:15) to yield 8 mg (80%) of 28.
[ ]D20 –14.4 (c 1.23, CHCl3).
IR: 3065, 2928, 2855, 1449, 1306, 1146, 1088, 1059, 1003, 920,
741, 691 cm–1.
1H NMR (200 MHz, CDCl3): = 0.38 (1 H, q, J = 6.2 Hz, H -3),
0.79 (1 H, ddd, J = 3.0, 6.2, 9.8 Hz, H -3), 1.14 (1 H, m, H-2), 1.58
(2 H, m, -CH2CH2SO2Ph), 3.17 (3 H, m, H-1, –CH2CH2SO2Ph),
3.37 (3 H, s, -OCH2OCH3), 4.58 (2 H, s, -OCH2OCH3), 7.58 (3 H,
m, -SO2Ph), 7.87 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 12.7 (C-3), 17.6 (C-2), 25.3
(-CH2CH2SO2Ph), 55.7 (-CH2CH2SO2Ph), 55.9 (-OCH2OCH3),
IR: 2930, 2868, 1690, 1449, 1308, 1146, 1086 cm–1.
1H NMR (200 MHz, CDCl3): = 2.79 (2 H, m, H-4), 3.27 (2 H, t,
J = 7.4 Hz, H-5), 6.09 (1 H, dd, J = 15.8, 7.6 Hz, H-2), 6.76 (1 H,
dt, J = 15.8, 6.6 Hz, H-3), 7.64 (3 H, m, -SO2Ph), 7.93 (2 H, m,
-SO2Ph), 9.47 (1 H, d, J = 7.6 Hz, -CHO).
56.3 (C-1), 96.9 (-OCH2OCH3), 128.2 (Cortho, -SO2Ph), 129.5 (Cmeta
-SO2Ph), 133.9 (Cpara, -SO2Ph), 139.3 (Cipso, -SO2Ph).
MS: m/z (%) = 271 (1) [M + 1+], 136 (20), 114 (10), 77 (100).
,
Hydrogenation Reaction; General Procedure
(+)-(1R,2S)-2-(2-Benzenesulfonylethyl)-1-(tetrahydropyran-2-
yloxy)-cyclopropane (29)
To a soln of 18 (13 mg, 0.04 mmol) in EtOAc (1 mL) was added a
catalytic amount of PtO2. The mixture was left to stir under hydro-
gen for 15 h. The mixture was then filtered through celite and the
solvent evaporated in vacuo. If necessary, the product was purified
(–)-(1R,2R)-2-(2-Benzenesulfonylethyl)-1-methoxymethoxy-
cyclopropane (36)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Compound 21 (11 mg, 0.04 mmol) was
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Cyclopropanols from Allylic Sulfones
61
reacted for 15 h to yield 9 mg (80%) of the hydrogenated product
36.
[ ]D20 –28.1 (c 0.88, CHCl3).
IR: 3067, 2924, 2851, 1447, 1306, 1146, 1088, 1045, 741, 691 cm–1.
1H NMR (200 MHz, CDCl3): = 0.22 (1 H, dt, J = 3.2, 6.2, 6.2 Hz,
H -3), 0.68 (1 H, dt, J = 9.2, 6.2, 6.2 Hz, H -3), 0.88 (1 H, m, H-2),
1.86 (2 H, m, -CH2CH2SO2Ph), 3.23 (2 H, m, -CH2CH2SO2Ph), 3.45
(3 H, m, -OCH2OCH3), 3.46 (1 H, dt, J = 3.4, 6.6, 6.6 Hz, H-1), 4.55
(1 H, d, J = 6.6 Hz, -OCHAHBOCH3), 4.60 (1 H, d, J = 6.6 Hz,
-OCHAHBOCH3), 7.58 (3 H, m, -SO2Ph), 7.90 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 11.3 (C-3), 15.6 (C-2), 21.5
(-CH2CH2SO2Ph), 54.1 (C-1), 56.0 (-OCH2OCH3), 56.3
(-CH2CH2SO2Ph), 97.1 (-OCH2OCH3), 128.3 (Cortho, -SO2Ph),
129.4 (Cmeta, -SO2Ph), 133.8 (Cpara, -SO2Ph), 139.2 (Cipso, -SO2Ph).
CH3OC6H4CH2-), 128.3 (Cortho, -SO2Ph), 129.4 (Cmeta, -SO2Ph),
129.6 (Cortho, p-CH3OC6H4CH2-), 130.2 (Cipso, p-CH3OC6H4CH2-),
133.7 (Cpara, -SO2Ph), 139.3 (Cipso, -SO2Ph), 159.2 (Cpara, p-
CH3OC6H4CH2-).
MS: m/z (%) = 347 (5) [M + 1+], 154 (40), 121 (100), 95 (40), 77
(70).
HRMS: m/z calcd for C19H23O4S, 347.1317; found, 347.1317.
(–)-(1R,2S)-2-(2-Benzenesulfonylethyl)-1-tert-butyldi-
methylsililoxy-cyclopropane (33)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Compound 24 (12 mg, 0.03 mmol) was
reacted for 1 h to yield 11 mg (90%) of the hydrogenated product
33.
[ ]D20 –36.4 (c 0.78, CHCl3).
IR: 2957, 2950, 2857, 1447, 1308, 1148, 1086, 873, 779 cm–1.
MS: m/z (%) = 271 (1) [M + 1+], 149 (20), 91 (40), 77 (100).
(–)-(1R,2S)-2-(2-Benzenesulfonylethyl)-1-(4-methoxy-
benzyloxy)-cyclopropane (32)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Compound 22 (11 mg, 0.03 mmol) was
reacted for 30 min to yield 3 mg (34%) of the hydrogenated product
32.
1H NMR (200 MHz, CDCl3): = 0.06 (6 H, s, MeASi, MeBSi), 0.27
(1 H, q, J = 5.8Hz, H -3), 0.65 (1 H, ddd, J = 2.8, 5.8, 9.4 Hz, H -
3), 0.85 (1 H, m, H-2), 0.86 [9 H, s, (CH3)3CSi], 1.34 (1 H, m,
-CHAHBCH2SO2Ph), 1.81 (1 H, m, -CHAHBCH2SO2Ph), 3.12 (3 H,
m, H-1, -CH2CH2SO2Ph), 7.59 (3 H, m, -SO2Ph), 7.90 (2 H, m,
-SO2Ph).
[ ]D20 –18.9 (c 0.37, CHCl3).
13C NMR (50 MHz, CDCl3): = –4.6 (MeA–Si, MeB–Si), 14.3 (C-
3), 18.2 [(CH3)3C–Si], 18.8 (C-2), 25.3 (-CH2CH2SO2Ph), 26.0
IR: 2922, 2853, 1613, 1514, 1447, 1304, 1260, 1146, 1086, 1032
cm–1.
MS: m/z (%) = 347 (5) [M + 1+], 121 (37), 99 (5), 49 (70).
[(CH3)3CSi], 53.4 (C-1), 55.7 (-CH2CH2SO2Ph), 128.2 (Cortho
,
-SO2Ph), 129.5 (Cmeta, -SO2Ph), 133.9 (Cpara, -SO2Ph), 139.5(Cipso
,
-SO2Ph).
1H NMR (200 MHz, CDCl3): = 0.33 (1 H, q, J = 6.2 Hz, H -3),
0.80 (1 H, ddd, J = 3.0, 6.2, 9.8 Hz, H -3), 1.14 (1 H, m, H-2), 1.57
(2 H, m, -CH2CH2SO2Ph), 3.00 (1 H, dt, J = 6.2, 3.0, 3.0 Hz, H-1),
3.11 (2 H, dd, J = 7.4, 8.8 Hz, -CH2CH2SO2Ph), 3.80 (3 H, s, p-
CH3OC6H4CH2-), 4.41 (1 H, s, p-CH3OC6H4CHAHB-), 4.42 (1 H, s,
p-CH3OC6H4CHAHB-), 6.85 (2 H, m, Hmeta p-CH3OC6H4CH2-), 7.22
(2 H, m, Hortho p-CH3OC6H4CH2-), 7.60 (3 H, m, -SO2Ph) 7.89 (2 H,
m, -SO2Ph).
MS: m/z (%) = 341 (25) [M+], 283 (35), 211 (8), 135 (25), 73 (100).
HRMS: m/z calcd for C17H29O3SSi, 341.1607; found, 341.1607.
(–)-(1R,2R)-2-(2-Benzenesulfonylethyl)-1-tert-butyldi-
methylsililoxy-cyclopropane (38)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Data are reported. Compound 25 (27
mg, 0.08 mmol) was reacted for 22 h to yield 18 mg (66%) of the
hydrogenated product 38.
[ ]D20 –36.8 (c 1.37, CHCl3).
IR: 2957, 2930, 2857, 1447, 1306, 1148, 1088, 839, 779 cm–1.
1H NMR (200 MHz, CDCl3): = 0.01 (3 H, s, MeASi), 0.04 (3 H, s,
MeBSi), 0.62 (2 H, m, H-3), 0.75 (1 H, m, H-2), 0.81 [9 H, s,
(CH3)3CSi], 1.71 (1 H, m, -CHAHB-CH2SO2Ph), 1.87 (1 H, m,
-CHAHB-CH2SO2Ph), 3.07–3.38 (3 H, m, H-1, -CH2CH2SO2Ph),
7.58 (3 H, m, -SO2Ph), 7.90 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 13.0 (C-3), 18.0 (C-2),
25.2 (-CH2CH2SO2Ph), 55.5 (p-CH3OC6H4CH2-), 55.8
(-CH2CH2SO2Ph), 58.6 (C-1), 72.7 (p-CH3OC6H4CH2-), 114.1
(Cmeta, p-CH3OC6H4CH2-), 128.2 (Cortho, -SO2Ph), 129.5 (Cmeta
-SO2Ph), 129.8 (Cortho, p-CH3OC6H4CH2-), 129.9 (Cipso
,
,
p-CH3OC6H4CH2-), 133.9 (Cpara, -SO2Ph), 139.3 (Cipso, -SO2Ph),
159.6 (Cpara, p-CH3OC6H4CH2-).
HRMS: m/z calcd for C19H23O4S, 347.1317; found, 347.1317.
(–)-(1R,2R)-2-(2-Benzenesulfonylethyl)-1-(4-methoxy-
benzyloxy)-cyclopropane (37)
This experiment was carried out based on the procedure given for
the hydrogenation reaction. Compound 23 (10 mg, 0.03 mmol) was
reacted for 18 h to yield 9 mg (92%) of the hydrogenated product
37.
13C NMR (50 MHz, CDCl3): = –5.0 (MeASi), –4.8 (MeBSi), 13.3
(C-3), 15.0 (C-2), 18.1 [(CH3)3CSi], 21.6 (-CH2CH2SO2Ph), 25.9
[(CH3)3CSi], 50.2 (C-1), 56.4 (-CH2CH2SO2Ph), 128.3 (Cortho
,
-SO2Ph), 129.4 (Cmeta, -SO2Ph), 133.7 (Cpara, -SO2Ph), 139.5 (Cipso
,
-SO2Ph).
MS: m/z (%) = 341 (35) [M+], 283 (40), 199 (5), 135 (25), 73 (100).
HRMS: m/z calcd for C17H29O3SSi, 341.1607; found, 341.1609.
[ ]D20 –9.8 (c 0.53, CHCl3).
IR: 2922, 2853, 1615, 1516, 1447, 1304, 1248, 1146, 1088, 1034
cm–1.
(–)-(1R,2S)-2-(2-Benzenesulfonylethyl)-cyclopropanol (30)
To a soln of 26 (27 mg, 0.09 mmol) in EtOAc (1 mL) was added a
catalytic amount of PtO2. The mixture was left to stir under hydro-
gen for 15 h. It was filtered then through celite and the solvent evap-
orated in vacuo. The product was purified by column
chromatography (hexane–EtOAc, 7:3) to yield 10 mg (48%) of 30.
1H NMR (200 MHz, CDCl3): = 0.20 (1 H, dt, J = 3.4, 6.2, 6.2 Hz,
H -3), 0.62 (1 H, dt, J = 9.2, 6.2, 6.2 Hz, H -3), 0.85 (1 H, m, H-2),
1.87 (2 H, q, J = 8.0 Hz, -CH2CH2SO2Ph), 3.25 (3 H, m, H-1,
-CH2CH2SO2Ph), 3.81 (3 H, s, p-CH3OC6H4CH2-), 4.38 (1 H, s, p-
CH3OC6H4CHAHB-), 4.40 (1 H, s, p-CH3OC6H4CHAHB-), 6.86 (2
H, m, Hmeta p-CH3OC6H4CH2-), 7.17 (2 H, m, Hortho p-
CH3OC6H4CH2-), 7.57 (3 H, m, -SO2Ph), 7.90 (2 H, m, -SO2Ph).
13C NMR (50 MHz, CDCl3): = 11.4 (C-3), 16.2 (C-2), 21.4
(-CH2CH2SO2Ph), 55.5 (p-CH3OC6H4CH2-), 56.2 (C-1), 56.4
(-CH2CH2SO2Ph), 72.9 (p-CH3OC6H4CH2-), 114.0 (Cmeta, p-
To a soln of 29 (8 mg, 0.02 mmol) in MeOH (1 mL) was added a
catalytic amount of p-toluensulfonic acid monohydrate. The mix-
ture was left to stir for 2 h. The soln was then diluted with Et2O, and
washed with a soln of NaHCO3 (5%), H2O and sat. brine. The or-
ganic phase was dried with anhyd Na2SO4, filtered and removed the
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York

62
D. Díez et al.
PAPER
solvent in vacuo. The product was purified by column chromatog-
[ ]D20 –8.5 (c 0.46, CHCl3).
raphy (hexane–EtOAc, 7:3) to yield 5 mg (79%) of 30.
IR: 3200–3600, 3063, 2926, 2855, 1447. 1304, 1144, 1086, 689,
665 cm–1.
1H NMR (200 MHz, CDCl3): = 0.21 (1 H, m, H -3), 0.72 (2 H, m,
H -3, H-2), 1.93 (2 H, m, -CH2CH2SO2Ph), 2.26 (1 H, br s, -OH),
3.26 (2 H, m, -CH2CH2SO2Ph), 3.52 (1 H, dt, J = 3.2, 6.4, 6.4 Hz,
H-1), 7.61 (3 H, m, -SO2Ph), 7.92 (2 H, m, -SO2Ph).
Compound 31 (10 mg, 0.04 mmol) was dissolved in 1 mL of the
mixture: THF–H2–HCl 6 N (1:5:2). The mixture was left to stir for
15 h before the addition of sat. NaCl soln (1 mL). The product was
extracted into EtOAc (3 ). The organic extracts were dried over
anhyd Na2SO4, filtered and the solvent removed in vacuo. The prod-
uct was purified by flash silica column chromatography (hexane–
EtOAc, 7:3) to yield 7 mg (60%) of 30.
13C NMR (50 MHz, CDCl3): = 13.3 (C-3), 16.7 (C-2), 20.7
(-CH2CH2SO2Ph), 49.9 (C-1), 56.6 (-CH2CH2SO2Ph), 128.2 (Cortho
-SO2Ph), 129.5 (Cmeta, -SO2Ph), 133.9 (Cpara, -SO2Ph), 139.5 (Cipso
-SO2Ph).
,
,
To a soln of 32 (4 mg, 0.01 mmol) in EtOAc (1 mL) was added a
catalytic amount of Pd–C. The mixture was left to stir under hydro-
gen for 1 h. It was then filtered through celite and the solvent evap-
orated in vacuo. The product was purified by column
chromatography (hexane–EtOAc, 7:3) to yield 1 mg (42%) of 30.
MS: m/z (%) = 226 (5) [M+] 184 (15), 143 (65), 125 (30), 104 (20),
77 (100), 67 (25).
HRMS: m/z calcd for C11H14O3S, 226.0664; found, 226.0639.
To a soln of 33 (8 mg, 0.02 mmol) in THF (0.5 mL) was added tre-
trabutylammonium fluoride 1.0 M soln (34 mL, 0.03 mmol). The
mixture was left to stir for 20 h. Then, it was diluted with EtOAc,
washed with H2O and sat. brine. The organic layer was dried over
anhyd Na2SO4, filtered and concentrated. The product was purified
by column chromatography (hexane–EtOAc, 7:3) to yield 4 mg
(78%) of 30.
Acknowledgment
We thank the CICYT (BQU 2001-1034), Junta de Castilla y León
(SA 13:00B) and Universidad de Salamanca for a doctoral fel-
lowship to P. G. G. and for financial support of this research. We
gratefully acknowledge the Mass Spectrometry and NMR Services
of Universidad de Salamanca.
[ ]D20 –17.2 (c 0.43, CHCl3).
IR: 3200–3600, 2926, 2855, 1447, 1304, 1142, 1086, 739, 689 cm–1.
1H NMR (400 MHz, CDCl3): = 0.37 (1 H, q, J = 6.0 Hz, H -3),
0.76 (1 H, ddd, J = 2.8, 5.6, 9.2 Hz, H -3), 0.95 (1 H, m, H-2), 1.56–
1.73 (2 H, m, -CH2CH2SO2Ph), 3.18 (2 H, ddd, J = 4.0, 6.4, 8.8 Hz,
-CH2CH2SO2Ph), 3.25 (1 H, dt, J = 6.4, 2.8, 2.8 Hz, H-1), 7.58 (2
H, m, -SO2Ph), 7.65 (1 H, m, -SO2Ph), 7.91 (2 H, m, -SO2Ph).
References
(1) Kazuta, Y.; Matsuda, A.; Shuto, S. J. Org. Chem. 2002, 67,
1669; and references cited therein.
(2) (a) Donaldson, W. A. Tetrahedron 2001, 57, 8589; and
references cited therein. (b) Esposito, A.; Taddei, M. J. Org.
Chem. 2000, 65, 9245.
13C NMR (50 MHz, CDCl3): = 14.9 (C-3), 19.6 (C-2), 25.2
(-CH2CH2SO2Ph), 52.8 (C-1), 56.0 (-CH2CH2SO2Ph), 128.2 (Cortho
-SO2Ph), 129.5 (Cmeta, -SO2Ph), 133.9 (Cpara, -SO2Ph), 139.4 (Cipso
-SO2Ph).
,
,
(3) For asymmetric synthesis of disubstituted cyclopropanols in
enantiomerically pure form from boronic esters see:
(a) Pietruszka, J.; Widenmeyer, M. Synlett 1997, 977.
(b) Fontani, P.; Carboni, B.; Vaultier, M.; Maas, G. Synthesis
1991, 605. (c) Imai, T.; Mineta, H.; Nishida, S. J. Org.
Chem. 1990, 55, 4986. (d) Pietruszka, J.; Witt, A. J. Chem.
Soc., Perkin Trans. 1 2000, 4293. (e) Luithle, J. E. A.;
Pietruszka, J.; Witt, A. Chem. Commun. 1998, 2651.
(f) Taylor, R. E.; Schmidt, M. J.; Yuan, H. Org. Lett. 2000,
2, 601; and references cited therein. (g) Baird, M. S.; Huber,
A. M.; Clegg, W. Tetrahedron 2001, 57, 9849.
(4) For lead references, see (a) Salaün, J. The Chemistry of the
Cyclopropyl Group, In Rearrangements Involving the
Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York,
1987, 809. (b) de Meijere, A. Carbocyclic Three and Four-
membered Ring Systems in Methods of Organic Chemistry
(Houben–Weyl), Vol. E 17a–f; Thieme: New York, 1997.
(c) Sylvestre, I.; Olivier, J.; Salaün, J. Tetrahedron Lett.
2001, 42, 4991; and references cited therein. (d) Shaffer, C.
L.; Morthon, M. D.; Hanzlik, R. P. J. Am. Chem. Soc. 2001,
123, 8502. (e) Kulinkovich, O. G.; de Meijere, A. Chem.
Rev. 2000, 100, 2789; and references cited therein.
(5) (a) Díez, D.; San Feliciano, S. G.; Marcos, I. S.; Basabe, P.;
Garrido, N. M.; Urones, J. G. Synthesis 2001, 1069.
(b) Díez, D.; Templo Beneitez, M.; Marcos, I. S.; Garrido, N.
M.; Basabe, P.; Urones, J. G. Synlett 2001, 655.
MS: m/z (%) = 226 (5) [M+], 184 (10), 143 (60), 125 (25), 84 (85),
77 (90).
HRMS: m/z calcd for C11H14O3S, 226.0664; found, 226.0673.
(–)-(1R,2R)-2-(2-Benzenesulfonylethyl)-cyclopropanol (35)
To a soln of 34 (3 mg, 0.01 mmol) in MeOH (1 mL) was added a
catalytic amount of p-toluensulfonic acid monohydrate. The mix-
ture was left to stir for 15 h. The soln was then diluted with Et2O,
and washed with a soln of NaHCO3 (5%), H2O and sat. brine. The
organic phase was dried with anhyd Na2SO4, filtered and the solvent
removed in vacuo. The product was purified by column chromatog-
raphy (hexane–EtOAc, 7:3) to yield 2 mg (95%) of 35.
Compound 36 (10 mg, 0.04 mmol) was dissolved in the mixture:
THF–H2O–HCl 6 N (1:5:2, 1 mL). The mixture was left to stir for
15 h before the addition of sat. NaCl soln (1 mL). The product was
extracted into EtOAc (3 ). The organic extracts were dried over
anhyd Na2SO4, filtered and the solvent removed in vacuo. The prod-
uct was purified by flash silica column chromatography (hexane–
EtOAc, 7:3) to yield 6 mg (72%) of 35.
To a soln of 37 (5 mg, 0.01 mmol) in EtOAc (1 mL) was added a
catalytic amount of Pd–C. The mixture was left to stir under hydro-
gen for 15 h. It was then filtered through celite and the solvent evap-
orated in vacuo. The product was purified by column
chromatography (hexane–EtOAc, 7:3) to yield 2 mg (53%) of 35.
(6) Díez, D.; Garcia, P.; Pacheco, M. P.; Marcos, I. S.; Garrido,
N. M.; Basabe, P.; Urones, J. G. Synlett 2002, 355.
(7) Kociénski, P. J. In Protecting Groups; Georg Thieme
Verlag: Stuttgart and New York, 1994.
(8) (a) Reissig, H.-U.; Böhn, I. J. Am. Chem. Soc. 1982, 104,
1735. (b) Padwa, A.; Wannamaker, M. W. Tetrahedron Lett.
1986, 27, 2555. (c) Militzer, H.-C.; Schömenauer, S.; Otte,
C.; Puls, C.; Hain, J. B. S.; de Meijere, A. Synthesis 1993,
998; and references cited therein.
To a soln of 38 (17 mg, 0.05 mmol) in THF (0.5 mL) was added tet-
rabutyl ammonium fluoride 1.0 M soln (77 mL, 0.08 mmol). The
mixture was left to stir for 3 h. Then, it was diluted with EtOAc and
washed with H2O and sat. brine. The organic layer was dried over
anhyd Na2SO4, filtered and concentrated. The product was purified
by column chromatography (hexane–EtOAc, 7:3) to yield 9 mg
(78%) of 35.
Synthesis 2003, No. 1, 53–62 ISSN 0039-7881 © Thieme Stuttgart · New York