Syntheses of both enantiomers of 1,7-dioxaspiro[5.5]undecane: Pheromone components of the olive fruit-fly Dacus oleae from a new chiral intermediate, the (S(s))-2-(p-tolylsulfinyl)prop-2-en-1-ol

Article abstract of DOI:10.1055/s-1999-3467

Both enantiomers of 1,7-dioxaspiro[5.5]undecane, the pheromone components of the olive fruit-fly Dacus oleae have been synthesized from a new chiral sulfoxide, (Ss)-2-(p-tolylsulfinyl)prop-2-en-1-ol via hetero Diels-Alder reaction, chromatographic separation of the diastereomers on a silica gel column and desulfurization over Raney nickel as key steps.

Full text of DOI:10.1055/s-1999-3467

PAPER
783
Syntheses of Both Enantiomers of 1,7-Dioxaspiro[5.5]undecane: Pheromone
Components of the Olive Fruit-Fly Dacus oleae from a New Chiral
Intermediate, the (Ss)-2-(p-Tolylsulfinyl)prop-2-en-1-ol
Patricia Hayes, Christian Maignan*
Laboratoire de Synthèse Organique (associé au CNRS), Faculté des Sciences, Avenue Olivier Messiaen, F-72085 Cedex 9, Le Mans, France
Fax +33(2)43833902; E-mail: maignan@aviion.univ-lemans.fr
Received 29 October 1998
At first, we examined the preparation of (SS)-1 from (RS)-
Abstract: Both enantiomers of 1,7-dioxaspiro[5.5]undecane, the
p-tolyl vinyl sulfoxide.9 Unfortunately, treatment of (RS)-
p-tolyl vinyl sulfoxide with lithium diisopropylamide fol-
lowed by addition of gaseous formaldehyde proved to be
pheromone components of the olive fruit-fly Dacus oleae have been
synthesized from a new chiral sulfoxide, (Ss)-2-(p-tolylsulfi-
nyl)prop-2-en-1-ol via hetero Diels–Alder reaction, chromato-
graphic separation of the diastereomers on a silica gel column and unsuccessful. The reduction of ethyl 2-(p-tolylsulfi-
desulfurization over Raney nickel as key steps.
nyl)acrylate with NaBH4, LiAlH4 or DIBALH furnished
only the saturated ester. Finally, the synthesis of (SS)-1
was achieved in one step from (–)-menthyl p-toluenesulfi-
nate [(–)-3]. Indeed, substitution reaction of (–)-3 with
lithium 2-lithioprop-2-en-1-olate (4)10 afforded directly
(SS)-1 in 60% yield (Scheme 1).
Key words: insect pheromone, hetero Diels–Alder reaction, chiral
1,7-dioxaspiro[5.5]undecane, chiral sulfinyl heterodiene, (Ss)-2-(p-
tolylsulfinyl)prop-2-en-1-ol
In a previous report,1 we disclosed the high reactivity in
hetero Diels–Alder reaction, of the in situ generated (±)-
2-(p-tolylsulfinyl)acrolein (6) obtained by oxidation of
(±)-2-(p-tolylsulfinyl)prop-2-en-1-ol (1). This new unsta-
ble intermediate diene reacts with different enol ethers
and leads to functionalized dihydropyran and spiroketal
derivatives. In order to demonstrate the utility of the pro-
cedure developed, we examined here the synthesis of 1,7-
dioxaspiro[5.5]undecane (2) using the enantiomerically
pure (SS)-2-p-(tolylsulfinyl)prop-2-en-1-ol (1), not yet de-
scribed, as chiral sulfinyl source.
Scheme 1
The hetero Diels–Alder reaction between 2-methylenetet-
rahydropyran (5) and (SS)-2-(p-tolylsufinyl)acrolein (6)
generated in situ by oxidation at room temperature of (SS)-
1 (MnO2 (10 equiv)/CH2Cl2, 8 h) affords (SS,6R)- and
(SS,6S)-3-(p-tolysulfinyl)-1,7-dioxaspiro[5.5]undec-2-
ene (7) as a mixture of diastereomers in the ratio 50:50.
However, the lack of chiral induction is compensated by
the ease of the separation of the diastereoisomers on a sil-
ica gel column.
1,7-Dioxaspiro[5.5]undecane (2) was shown as the main
component of the Dacus oleae (olive fruit-fly) by Baker,
Francke and their co-workers2 in 1980; the (+)-(S)-2 enan-
tiomer is active against the female while the (–)-(R)-2
enantiomer is active against the male species.
Because of the difficulty encountered in controlling the
stereochemistry at the spiro center, only three groups3–6
have succeeded in the enantioselective syntheses of (–)-
(R)-2 and the (+)-(S)-2; from D-glucose by Redlich and
Francke,4 from (S)-malic acid by Mori,5 and from hyd-
roxybutylated chiral vinylic sulfoxide by Iwata.6 Recent-
ly, two examples of selective separation have been also re-
Hydrogenation of (+)-(SS,6S)-7 and (–)-(SS,6R)-7 with
Raney nickel in methanol12 involving reduction of the
C=C bond and desulfurization affords (+)-(S)-2 and (–)-
(R)-2 in 62 and 60% yield, respectively (Scheme 2). The
spectral properties of the synthetic products are in accor-
dance with those reported in the literature.5,6
ported
using
hexakis(2,3,6-tri-O-methyl)-a-7
or
hexakis(2,6-di-O-methyl)-b-cyclodextrin.8
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784
P. Hayes, C. Maignan
PAPER
Scheme 2
(R)-1,7-Dioxaspiro[5.5]undec-2-ene (8) is obtained in
69% yield by treatment of (SS, 6R)-7 with Raney nickel in
anhydrous tetrahydrofuran12,13 (Scheme 3).
were performed at the C.N.R.S. (Gif-sur-Yvette). Flash chromatog-
raphy were carried out on SDS silica gel A.C.C. (230–400 mesh)
and on activated neutral aluminum oxide (50–200 micron).
2-Bromoprop-2-en-1-ol10
Anhyd HBr (40g, 0.49 mol) was bubbled into a suspension of
Et4NBr (113.3 g, 0.54 mol) and CH2Cl2 (450 mL) at 0°C to give a
clear yellow solution. The mixture was stirred at r.t. for 10 min.
Prop-2-yn-1-ol (25.5 g, 0.45 mol) was added slowly and the mixture
was stirred for 1 h and then refluxed for 2 h. The mixture was
cooled, poured into Et2O (400 mL) and the precipitate formed was
filtered through a short pad of silica gel and washed with Et2O (150
mL). The combined Et2O layers were dried and evaporated to give
39.4g (63%) (Lit.10 72%) of 2-bromoprop-2-en-1-ol as a colorless
oil; bp 150°C/760 Torr.
1H NMR (CDCl3/TMS): d = 3.23 (s, 1 H, OH), 4.2 (t, J = 1.4 Hz, 2
H, CH2OH), 5.57 (dd, J = 1.4, 0.9 Hz, 1 H), 5.90 (dd, J = 1.4, 0.9
Hz, 1 H).
13C NMR (CDCl3/TMS): d = 67.36, 116.21, 132.27.
Scheme 3
Enantiomeric purities of (+)-(S)-2 (80% ee), (–)-(R)-2
(94.5% ee) and (–)-(R)-8 (94% ee) were determined by
gas chromatography using a chiral column. The (+)-(S)-2
enantiomer seems to be less stable than the (–)-(R)-2.6b
2-(p-Tolylsulfinyl)prop-2-en-1-ol (1) is a suitable sub-
strate for the synthesis of spiroketal system, which is a
structural feature of many natural products. (SS)-1 is easily
obtained in one step and no isomerization of 2-methylene-
tetrahydropyran (5) was observed during the Diels–Alder
condensation.14
IR (neat): n = 3340 (vs), 2917 (s), 2863 (m), 1641 (s), 1448 (m),
1411 (m), 1234 (m), 1157 (m), 1045 (s), 976 (w), 893 cm–1 (s).
(SS)-2-(p-Tolylsulfinyl)prop-2-en-1-ol [(SS)-(+)-(1)]
To a solution of 2-bromoprop-2-en-1-ol (826 mg, 6.02 mmol) in
Et2O (16 mL) at –78°C was added slowly a 1.5 M solution of t-BuLi
(10 mL) in pentane. The mixture was quickly warmed to 0°C and
stirred for 4 h. The mixture was added to a solution of (–)-3 (590
mg, 2 mmol) in THF (15 mL) at –78°C and the stirring was contin-
ued for 10 min. The mixture was hydrolyzed with H2O and the
aqueous phase was extracted with CH2Cl2. The organic phases were
combined, dried (MgSO4), and concentrated. The final purification
was achieved by silica gel chromatography [eluent: Et2O/petroleum
ether (5:5), then pure Et2O] affording (+)-1 as a white solid; mp
28°C; [a]D +103.0 (c = 0.55, EtOH).
1H NMR (CDCl3/TMS): d = 2.41 (s, 3 H, CH3-Ar), 2.66 (m, 1 H,
OH), 4.02 (2 d, J = 8 Hz, 1 H, CH2OH), 4.31 (2 d, J = 5.3, 14 Hz, 1
H, CH2OH), 5.82 (s, 1 H, Hcis), 6.08 (s, 1 H, Htrans), 7.32 and 7.52 (4
H, J = 8 Hz, AA'BB' system).
13C NMR (CDCl3/TMS): d = 21.43, 59.57, 118.65, 125.03, 130.08,
138.52, 142.01, 153.39.
To conclude, we have developed a convenient two-step
procedure for the preparation of both (+)-(S) and (–)-(R)-
1,7-dioxaspiro[5.5]undecane (2) via an hetero Diels–Al-
der reaction and a facile diastereomer separation.
(–)-Menthyl p-toluenesulfinate was prepared according to the liter-
ature.15 Et2O and THF were distilled from Na/benzophenone prior
to use. Melting points were determined on a Reichert Thermovar
apparatus and are uncorrected. H (400 MHz) and 13C (100 MHz)
1
NMR spectra were recorded on a Bruker AC 400 instrument in
CDCl3 using TMS for 1H spectra and the solvent for 13C spectra as
internal reference. Multiplicities in the 13C spectra were determined
by DEPT experiments. IR spectra were recorded on a Mattson spec-
trometer. Specific optical rotations were measured with a Perkin-
Elmer Model 343 polarimeter at 20°C. Mass spectra were recorded
on a Finnigan instrument. Optical purities were determined on a
Hewlett-Packard HP6890 Series GC system equipped with a chiral
column (Restek b-DEX, 30 m, 120°C, helium). Elemental analyses
IR (KBr): n = 3369 (s), 3052 (m), 2921 (m), 2865 (m), 1596 (s),
1492 (s), 1450 (m), 1398 (m), 1303 (w), 1234 (w), 1178 (w), 1081
(s), 1039 (s), 931 (s), 811 cm–1 (s).
Synthesis 1999, No. 5, 783–786 ISSN 0039-7881 © Thieme Stuttgart · New York

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Syntheses of Both Enantiomers of 1,7-Dioxaspiro[5.5]undecane
785
Anal. calcd for C10H12SO2 (196.3): C, 61.19; H, 6,16; S, 16.33.
Found C, 61.40; H, 6,42; S, 16.46.
(+)-(S)-1,7-Dioxaspiro[5.5]undecane [(+)-(S)-2]
Raney Ni (W-2, ca 1g) was added to a solution of (+)-(SS,6S)-7 (54
mg ; 0.18 mmol) in anhyd MeOH (8 mL) and the mixture was
stirred at 65°C for 1 h. The catalyst was removed by filtration and
the filtrate was concentrated carefully under vacuum at 0°C. The
oily residue was chromatographed on alumina with pentane as elu-
ent to give 20 mg (62%) of (+)-(S)-2 as a colorless oil; [a]D +97.0 (c
= 0.25, pentane) [Lit5,6 [a]D +119.0 (c = 1.41, pentane); [a]D +123.0
(c = 0.234, pentane)].
(–)-(SS,6R)-3-(p-Tolylsulfinyl-1,7-dioxaspiro[5.5]undec-2-ene
and (+)-(SS,6S)-3-(p-Tolylsulfinyl)-1,7-dioxaspiro[5.5]undec-2-
ene [(–)-(SS,6R) and (+)-(SS,6S)-7]
To a solution of (SS)-1 (576 mg, 2.94 mmol) in CH2Cl2 (35 mL) was
added an excess of activated MnO2 (2.61 g, 30 mmol) and 2-meth-
ylenetetrahydropyran (5; 864 mg, 8.8 mmol). After 8 h at r.t., the so-
lution was concentrated and the residue was diluted with Et2O. The
excess of MnO2 was removed by filtration through a short pad of sil-
ica gel (Et2O). The residue (diastereomeric ratio = 50:50) was puri-
fied by chromatography on silica gel (20 g) (eluent: 1% MeOH in
CH2Cl2) to afford 250 mg (29%) of (–)-(SS,6R)-7 as a white solid,
200 mg (23 %) of (+)-(SS,6S)-7 as a colorless oil, and 80 mg (9%)
of a mixture of (–)-7 and (+)-7.
The IR, 1H NMR, and MS of (S)-2 were found to be identical with
those of (R)-2.
(–)-(R)-1,7-Dioxaspiro[5.5]undec-2-ene [(–)-(R)-8]
Raney Ni (W-2, ca 1g) was added to a solution of (–)-(SS,6R)-7 (110
mg, 0.37 mmol) in anhyd THF (30 mL) and the mixture was stirred
at r.t. for 1 h. The catalyst was removed by filtration and the filtrate
was concentrated carefully under vacuum at 0°C. The oily residue
was chromatographed on alumina with pentane to give 40 mg
(69%) of (–)-(R)-8 as a colorless oil; [a]D –141.0 (c = 0.37, pen-
tane).
1H NMR (CDCl3/TMS): d = 1.41–1.90 (m, 9 H), 2.11–2.21 (m, 1
H), 3.64–3.7 (m, 1 H), 3.81 (dt, J = 11.4, 3 Hz, 1 H), 4.76–4.78 (m,
1 H), 6.25 (m, 1 H).
13C NMR (CDCl3/TMS): d = 16.71, 18.52, 25.41, 32.31, 34.69,
61.79, 95.57, 101.58, 140.45.
MS (EI, 70 eV): m/z (%) = 155 (M+ + 1, 1.7), 154 (M+, 6.7), 136 (3),
126 (14), 111 (3.8), 98 (100), 83 (20), 70 (13), 55 (33), 39 (58).
Anal. calcd for C16H20SO3 (292.4): C, 65.72; H, 6.89; S, 10.96.
Found C, 65.67; H, 6.64; S, 10.88.
(–)-(7): mp 85°C; [a]D –195.0 (c = 0.44, CH2Cl2).
1H NMR (CDCl3/TMS): d = 1.37–1.38 (m, 7 H), 1.70–1.91 (m, 3
H), 2.36 (s, 3 H), 3.59–3.62 (m, 1 H), 3.68–3.75 (m, 1 H), 7.17 (s, 1
H), 7.25-7.39 (4 H, J = 8.2 Hz, AA'BB' system).
13C NMR (CDCl3/TMS): d = 11.21, 19.76, 21.19, 25.08, 31.97,
33.68, 62.02, 97.75, 120.19, 124.47, 129.54, 139.08, 140.17,
147.77.
IR (KBr): n = 3048 (w), 3020 (w), 2945 (s), 2850 (m), 1631 (s),
1492 (m), 1442 (m), 1373 (w), 1288 (w), 1275 (w), 1232 (m), 1203
(s), 1186 (m), 1175 (m), 1147 (m), 1101 (m), 1078 (m), 1033 (s),
1022 (s), 970 (s), 945 (w), 887 (w), 862 (m), 844 (m), 812 (m), 763
(w), 733 (w), 700 cm–1 (w).
IR (neat): n = 3060 (w), 2941 (s), 2873 (m), 2848 (m), 1654 (s),
1440 (w), 1371 (w), 1274 (w), 1248 (w), 1222 (s), 1180 (w), 1145
(w), 1105 (m), 1080 (m), 1066 (s), 1045 (m), 1026 (s), 1001 (m),
974 (m), 883 (w), 868 (m), 812 (w), 765 cm–1 (w).
(+)-7: oil; [a]D +106.0 (c = 0.25, CH2Cl2).
1H NMR (CDCl3/TMS): d = 1.37–1.69 (m, 8 H), 1.78-1.88 (m, 2 H),
2.35 (s, 3 H), 3.66–3.71 (m, 1 H), 3.77–3.84 (m, 1 H), 7.16 (s, 1 H),
7.27–7.43 (4 H, J = 8.2 Hz, AA'BB' system).
13C NMR (CDCl3/TMS): d = 12.67, 18.02, 21.19, 24.65, 31.62,
33.29; 62.08, 97.86, 119.98, 124.53, 129.59, 139.61, 140.41,
147.88.
References
(1) Hayes, P.; Maignan, C. Synlett 1994, 409.
(2) Baker, R.; Herbert, R.; Howse, P.E.; Jones, O.T.; Francke, W.;
Reith, W. J.Chem. Soc., Chem. Commun. 1980, 52.
(3) For reviews, see:
(a) Fletcher, M.T.; Kitching, W. Chem. Rev. 1995, 95, 789.
(b) Mori, K. The Total Synthesis of Natural Products,
Apsimon, J., Ed.; Wiley: New York, 1992, Vol. 9, p 381.
(4) Redlich, H.; Francke, W. Angew. Chem. 1984, 96, 506;
Angew. Chem., Int. Ed. Engl. 1984, 23, 519.
IR (neat): n = 3048 (w), 3020 (w), 2945 (s), 2850 (m), 1631 (s),
1492 (m), 1442 (m), 1373 (w), 1288 (w), 1275 (w), 1232 (m), 1203
(s), 1186 (m), 1175 (m), 1147 (m), 1101 (m), 1078 (m), 1033 (s),
1022 (s), 970 (s), 945 (w), 887 (w), 862 (m), 844 (m), 812 (m), 763
(w), 733 (w), 700 cm–1 (w).
(5) (a) Mori, K.; Uematsu, T.; Watanabe, H.; Yanagi, K.; Minobe,
M. Tetrahedron Lett. 1984, 25, 3875.
(b) Mori, K.; Watanabe, H.; Yanagi, K.; Minobe, M.
Tetrahedron 1985, 41, 3663.
(6) a) Iwata, C.; Fujita, M.; Hattori, K.; Uchida, S. Tetrahedron
Lett. 1985, 26, 2221.
(–)-(R)-1,7-Dioxaspiro[5.5]undecane [(–)-(R)-(2)]
Raney Ni (W-2, ca 1 g) was added to a solution of (–)-(SS,6R)-7 (77
mg, 0.26 mmol) in anhyd MeOH (10 mL) and the mixture was
stirred at 65°C for 1 h. The catalyst was removed by filtration and
the filtrate was concentrated carefully under vacuum. The oily resi-
due was chromatographed on alumina with pentane as eluent to give
25 mg (60%) of (–)-(R)-2 as a colorless oil; [a]D –118.0 (c = 0.2,
pentane) [Lit5,6 [a]D –121.0 (c = 1.84, pentane); [a]D –128.0 (c =
0.503, pentane)].
1H NMR (CDCl3/TMS): d = 1.39–1.63 (m, 10 H), 1.77–1.86 (m, 2
H), 3.58–3.72 (m, 4 H).
13C NMR (CDCl3/TMS): d = 18.52, 25.30, 35.73, 60.34, 94.98.
MS (EI, 70 eV): m/z (%) = 156 (M+, 10), 101 (58), 83 (91), 55 (83),
(b) Iwata, C.; Fujita, M.; Kunoki, T.; Hattori, K.; Uchida, S.;
Imanishi, T. Chem. Pharm. Bull. 1988, 36, 3257.
(7) Yannakopoulou, K.; Mentzafos, D.; Mavridis, K.; Dandika,
K. Angew. Chem. 1996, 108, 2632; Angew. Chem., Int. Ed.
Engl. 1996, 35, 2480.
(8) Galons, H.; Gnaïn, J.; Rysanek, G.; Lebas, F.; Villain, F.;
Tsoucaris, G. Tetrahedron: Asymmetry 1993, 4, 181.
(9) Bonfand, E.; Gosselin, P.; Maignan, C. Tetrahedron:
Asymmetry 1993, 4, 1667.
(10) Corey, E. J.; Widiger, G. N. J. Org. Chem. 1975, 40, 2975.
(11) Al Dulayymi, A.R.; Al Dulayymi, J.R.; Baird, M.S.; Gerrard,
M.E.; Koza, G.; Harkins, S.D.; Roberts, E. Tetrahedron 1996,
52, 3409.
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Szwed, K.; Wichmann, J. Liebigs Ann. Chem. 1991, 275.
43 (95), 39 (100).
IR (neat): n = 2937 (s), 2867 (m), 1450 (m), 1384 (m), 1278 (m),
1230 (m), 1207 (m), 1178 (m), 1095 (s), 1066 (s), 989 (s), 937 (m),
877 (m), 796 cm–1 (m).
Synthesis 1999, No. 5, 783– 786 ISSN 0039-7881 © Thieme Stuttgart · New York

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P. Hayes, C. Maignan
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(13) Hayes, P.; Maignan, C. 12th Symposium on Chemistry of
Heterocyclic Compounds, 1996, Brno, Czech Republic.
(14) This phenomenon occurs frequently with sensitive and labile
methylene derivatives at high temperature, see:
Weichert, A.; Hoffmann, H. M. R. J. Org. Chem. 1991, 56,
4098.
Article Identifier:
1437-210X,E;1999,0,05,0783,0786,ftx,en;H10298SS.pdf
(15) Solladié, G.; Hutt, J.; Girardin, A. Synthesis 1987, 173.
Synthesis 1999, No. 5, 783–786 ISSN 0039-7881 © Thieme Stuttgart · New York