PAPER
Synthesis of (–)-Methylenolactonin
133
tert-Butyldimethylsilyl (S,S)-4-Acetoxy-3-[(E)-hept-1-enyl]-
talunya for a doctorate studentship to J. O., and the Universitat de
Barcelona for a doctorate studentship to M. L.
nonanoate (18)
Pale-yellow oil; Rf 0.55 (hexane–EtOAc, 9:1); [ ]D20 –4.4 (c = 0.9,
CHCl3).
References
IR (film): 2930, 1750, 1729, 1220 cm–1.
(1) (a) Pichon, M.; Figadère, B. Tetrahedron: Asymmetry 1996,
7, 927. (b) Whitesell, J. K. Chem. Rev. 1989, 89, 1581.
(c) Chong, J. M.; Clarke, I. S.; Koch, I.; Olbach, P. C.;
Taylor, N. J. Tetrahedron: Asymmetry 1995, 6, 409.
(d) Kim, M. J.; Lee, I. S. Synlett 1993, 767.
(2) (a) Otten, S.; Fröhlich, R.; Hanfe, G. Tetrahedron:
Asymmetry 1998, 9, 189. (b) Julienne, K.; Metzner, P.;
Henryon, V.; Greiner, A. J. Org. Chem. 1998, 63, 4532.
(3) (a) Burk, M. J.; Feaster, J. E.; Harlow, R. L. Tetrahedron:
Asymmetry 1991, 2, 569. (b) Burk, M. J.; Harper, T. G. P.;
Kalberg, C. S. J. Am. Chem. Soc. 1995, 117, 4423; and
references cited therein. (c) Wiesaner, C.; Kratky, C.;
Weissensteiner, W. Tetrahedron: Asymmetry 1996, 7, 397.
(4) (a) Amador, M.; Ariza, X.; Garcia, J.; Sevilla, S. Org. Lett.
2002, 4, 4511. (b) Ariza, X.; Garcia, J.; López, M.;
Montserrat, L. Synlett 2001, 120.
1H NMR (CDCl3, 300 MHz): = 0.23 (s, 3 H, CH3Si), 0.24 (s, 3 H,
CH3Si), 0.87 (t, 6 H, J = 6.7 Hz, CH3CH2), 0.97 [s, 9 H, (CH3)3C],
1.25 (m, 14 H, CH2), 1.97 (dt, 2 H, J = 6.6, 6.6 Hz, CH2CH=CH),
2.04 (s, 3 H, CH3CO), 2.20 (dd, 1 H, J = 15.0, 9.6 Hz, HCHCO2),
2.42 (dd, 1 H, J = 15.0, 4.5 Hz, HCHCO2), 2.69 (m, 1 H,
CHCH=CH), 4.79 (m, 1 H, CHOAc), 5.23 (dd, 1 H, J = 15.3, 8.7
Hz, CH2CH=CH), 5.50 (td, 1 H, J = 15.3, 6.6 Hz, CH2CH=CH).
13C NMR (CDCl3): = –4.8 (CH3Si), 13.9 and 14.0 [CH3(CH2)4],
17.5 [(CH3)3C], 21.0, 22.5 and 24.7 (CH2), 25.5 (CH3CO), 25.7
[(CH3)3C], 31.3, 31,6, 31.9 and 32.5 (CH2), 38.1 (CHCH2CO), 43.4
(COCH2), 75.8 (CHO), 128.4 (CH=CHCH2), 133.7 (CH=CHCH2),
170.7 (C=O), 172.7 (C=O).
HRMS: FAB+ m/z calcd for C24H47O4Si (M+ + 1): 427.3244; found:
427.3243.
A similar experiment was carried out with (S,S)-4 (120 mg, 0.38
mmol), t-BuMe2SiCl (239 mg, 1.53 mmol) and a toluene solution of
KHMDS (0.5 M, 2.30 mL, 1.15 mmol) in anhyd THF (4 mL). In this
case, the residue was filtered through a pad of silica gel and the mix-
ture of the acid 17 and its silyl ester 18 was treated with THF (2 mL)
and aq LiOH (8 M, 1 mL) at 70 °C for 9 h. The solution was then
acidified with 2 M aq HCl (6 mL), additional THF (3 mL) was add-
ed and the mixture was heated at 50 °C for 6 h. CH2Cl2 (50 mL) was
added and the organic layer was separated and dried (MgSO4).
Evaporation of solvents and purification by flash chromatography
on silica gel (hexane–EtOAc, 95:5) gave 68 mg (70%) of lactone
(S,S)-15 as a yellowish oil.
(5) For an overview on the desymmetrization of meso and other
prochiral compounds in asymmetric synthesis, see:
(a) Willis, M. C. J. Chem. Soc., Perkin Trans. 1 1999, 1765.
(b) Magnunson, S. R. Tetrahedron 1995, 51, 2167.
(c) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev.
1993, 93, 1307.
(6) Park, B. K.; Nakagawa, M.; Hirota, A.; Nakayama, M. J.
Antibiot. 1988, 41, 751.
(7) (a) Saicic, R. N.; Zard, S. Z. Chem. Commun. 1996, 1631.
(b) Ghatak, A.; Sarkar, S.; Ghosh, S. Tetrahedron 1997, 53,
17335. (c) Mandal, P. K.; Maiti, G.; Roy, S. C. J. Org.
Chem. 1998, 63, 2829. (d) Loh, T.-P.; Lye, P.-L.
Tetrahedron Lett. 2001, 42, 3511.
(2S,3R)-5-Oxo-2-pentyl-3-tetrahydrofurancarboxylic Acid
[(–)-2]
(8) (a) Zhu, G.; Lu, X. J. Org. Chem. 1995, 60, 1087. (b) Zhu,
G.; Lu, X. Tetrahedron: Asymmetry 1995, 6, 885.
(c) Mawson, S. D.; Weavers, R. T. Tetrahedron 1995, 51,
11257. (d) Chandrasekharam, M.; Liu, R.-S. J. Org. Chem.
1998, 63, 9122. (e) Kongsaeree, P.; Meepowpan, P.;
Thebtaranonth, Y. Tetrahedron: Asymmetry 2001, 12, 1913.
(9) (a) de Azevedo, M. B. M.; Murta, M. M.; Greene, A. E. J.
Org. Chem. 1992, 57, 4567. (b) Murta, M. M.; de Azevedo,
M. B. M.; Greene, A. E. Synth. Commun. 1993, 23, 495.
(10) (a) Vaupel, A.; Knochel, P. Tetrahedron Lett. 1995, 36, 231.
(b) Takahata, H.; Uchida, Y.; Momose, T. J. Org. Chem.
1995, 60, 5628. (c) Drioli, S.; Felluga, F.; Forzato, C.; Nitti,
P.; Pitacco, G. Chem. Commun. 1996, 1289. (d) Sibi, M. P.;
Deshpande, P. K.; La Loggia, A. J. Synlett 1996, 343.
(e) Vaupel, A.; Knochel, P. J. Org. Chem. 1996, 61, 5743.
(f) Masaki, Y.; Arasaki, H.; Itoh, A. Tetrahedron Lett. 1999,
40, 4829. (g) Chhor, R. B.; Nosse, B.; Sörgel, S.; Böhm, C.;
Seitz, M.; Reiser, O. Chem.–Eur. J. 2003, 9, 260.
(11) In this connection it should be pointed out that the reduction
of related alk-2-ene-1,4-diones gives lower
To a stirred solution of (S,S)-15 (60 mg, 0.23 mmol) in CCl4 (0.5
mL), MeCN (0.5 mL) and H2O (0.75 mL) were added RuCl3 (2 mg,
0.009 mmol) and NaIO4 (209 mg, 0.97 mmol) at r.t. After 4 h, an
additional amount of NaIO4 (100 mg, 0.47 mmol) was added and
the mixture was vigorously stirred for 2 h. The reaction was
quenched by the addition of CH2Cl2 (20 mL), the phases were de-
canted and the aqueous layer was further extracted with more
CH2Cl2 (2 × 10 mL). The combined organic layers were dried
(MgSO4), filtered and the solvent was removed under vacuo. The
crude was purified by flash chromatography (CH2Cl2 –MeOH,
98:2) to give 33 mg of the known acid (–)-2; mp 102–103 °C (Lit.9a
20
mp 105–107 °C); Rf 0.16 (hexane–EtOAc, 2:1); [ ]D –53.3
(c = 0.25, CHCl3) {Lit.9a [ ]D20 –54 (c = 0.5, CHCl3)}.
IR (film): 3500, 2960, 2930, 1748, 1722, 1220 cm–1.
1H NMR (CDCl3, 300 MHz): = 0.90 (t, 3 H, J = 6.6 Hz, CH3CH2),
1.25–1.83 (m, 8 H, CH2), 1.97 (dt, 2 H, J = 6.6, 6.6 Hz,
CH2CH=CH), 2.04 (s, 3 H, CH3CO), 2.82 (dd, 1 H, J = 17.8, 9.9 Hz,
HCHCO2), 2.94 (dd, 1 H, J = 17.8, 8.2 Hz, HCHCO2), 3.10 (m, 1 H,
CHCO2H), 4.56–4.68 (m, 1 H, CHOCO), 8.35 (br s, 1 H, CO2H).
13C NMR (CDCl3): = 14.0 [CH3(CH2)4], 22.6, 25.0, 31.5, 32.1 and
35.5 (CH2), 45.5 (CHCO2H), 81.9 (CHO), 174.8 (C=O), 176.7
(C=O).
stereoselectivities: (a) Bach, J.; Berenguer, R.; Garcia, J.;
López, M.; Manzanal, J.; Vilarrasa, J. Tetrahedron 1998, 54,
14947. (b) Bach, J.; Berenguer, R.; Garcia, J.; Loscertales,
T.; Manzanal, J.; Vilarrasa, J. Tetrahedron Lett. 1997, 38,
1091.
(12) For a review, see: Corey, E. J.; Helal, C. J. Angew. Chem. Int.
Ed. 1998, 37, 1986.
MS (CI): m/z (%) = 218 (M + 18, 100).
(13) Chabaud, B.; Sharpless, K. B. J. Org. Chem. 1979, 44, 4202.
(14) (a) Amador, M.; Ariza, X.; Garcia, J.; Ortiz, J. Tetrahedron
Lett. 2002, 43, 2691. (b) Diez, R. S.; Adger, B.; Carreira, E.
M. Tetrahedron 2002, 58, 8341.
(15) An attempt to obtain (S,S)-5 by double addition of acetylene
to hexanal under similar conditions also failed, see: Sasaki,
Acknowledgment
This work was supported by the Ministerio de Educación y Cultura
(PB98-1272, DGESIC) and Direcció General de Recerca, Generali-
tat de Catalunya (2000SGR00021). We thank the Generalitat de Ca-
Synthesis 2004, No. 1, 128–134 © Thieme Stuttgart · New York