Download PDF
Synlett 2004(6): 1064-1068  
DOI: 10.1055/s-2004-822899
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Synthesis of Alkylidenecyclopropanes by the Julia-Lythgoe-type Olefination Using Sulfones and Sulfoxides

Angela M. Bernard*, Angelo Frongia, Pier Paolo Piras*, Francesco Secci
Dipartimento di Scienze Chimiche, Università di Cagliari, Complesso Universitario di Monserrato, S.S. 554, Bivio per Sestu, 09042 Monserrato (Cagliari), Italy
Fax: +39(070)6754388; e-Mail: pppiras@unica.it;
Further Information

Publication History

Received 19 January 2004
Publication Date:
25 March 2004 (online)

    Permissions and Reprints All articles of this category

Abstract

The first use of the Julia-Lythgoe-type olefination with cyclopropylsulfones and cyclopropylsulfoxides for the synthesis of alkylidenecyclopropanes is reported.

Key words

olefination - carbocycles - sulfones - sulfoxides - alkylidenecyclopropanes

    References

  • Reviews:
  • 1a Brandi A. Goti A. Chem. Rev.  1998,  98:  589 
    CrossrefPubMedGoogle Scholar
  • 1b Brandi A. Cicchi S. Cordero FM. Goti A. Chem. Rev.  2003,  103:  1213 
    CrossrefPubMedGoogle Scholar
  • For reviews on this topic see:
  • 2a Binger P. Buch HM. Top. Curr. Chem.  1987,  135:  77 
    Google Scholar
  • 2b Goti A. Cordero FM. Brandi A. Top. Curr. Chem.  1996,  178:  2 
    Google Scholar
  • 3 Noyori R. Odagi T. Takaya H. J. Am. Chem. Soc.  1970,  92:  5780 
    CrossrefGoogle Scholar
  • 4 Ohta T. Takaya H. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Pergamon Press; Oxford: 1991.  p.1185 
    Google Scholar
  • 5 Hsiao C.-N. Hannick SM. Tetrahedron Lett.  1990,  31:  6609 
    CrossrefGoogle Scholar
  • 6 Motherwell WB. Shipman M. Tetrahedron Lett.  1991,  32:  1103 ; and references therein
    CrossrefGoogle Scholar
  • 7 Trost BM. Angew. Chem., Int. Ed. Engl.  1986,  25:  1 
    Google Scholar
  • 8 Donaldson WA. Wang J. Cepa VG. Suson JD. J. Org. Chem.  1989,  54:  6056 
    Google Scholar
  • 9 Pisaneschi F. Cordero FM. Goti A. Paugam R. Ollivier J. Brandi A. Salaun J. Tetrahedron: Asymmetry  2000,  11:  897 
    CrossrefGoogle Scholar
  • 10 Salaun J. Rearrangements Involving the Cyclopropyl Group, In The Chemistry of the Cyclopropyl Group   Rappoport Z. Wiley; New York: 1987.  p.809 
    Google Scholar
  • 11 Salaun J. Conia JM. J. Chem. Soc., Chem. Commun.  1971,  1579 
    Google Scholar
  • 12 Salaun J. Champion J. Conia JM. Org. Synth.  1977,  57:  36 
    Google Scholar
  • 13 Salaun J. Top. Curr. Chem.  1988,  144:  1 
    Google Scholar
  • 14 Bernard AM. Floris C. Frongia A. Piras PP. Tetrahedron  2000,  56:  4555 
    CrossrefGoogle Scholar
  • 15 Suginome M. Matsuda T. Ito Y. J. Am. Chem. Soc.  2000,  122:  11015 
    CrossrefGoogle Scholar
  • 16 Ishiyama T. Momota S. Miyaura N. Synlett  1999,  1790 
    Article in Thieme ConnectGoogle Scholar
  • 17 Bessmertnykh AG. Blinov KA. Grishin YK. Donskaya NA. Tveritinova EV. Yurieva NM. Beletskaya IP. J. Org. Chem.  1997,  62:  6069 
    CrossrefGoogle Scholar
  • 18 Chatani N. Takeyasu T. Hanafusa T. Tetrahedron Lett.  1988,  29:  3979 
    CrossrefGoogle Scholar
  • 19 Nakamura I. Itagaki H. Yamamoto Y. J. Org. Chem.  1998,  63:  6458 
    Google Scholar
  • 20 Camacho DH. Nakamura L. Saito S. Yamamoto Y. Angew. Chem. Int. Ed.  1999,  38:  3365 
    CrossrefGoogle Scholar
  • 21 Tsukada N. Shibuya A. Nakamura I. Kitahara H. Yamamoto Y. Tetrahedron  1999,  55:  8833 
    CrossrefGoogle Scholar
  • For the aminoacid hypoglycine see:
  • 22a Hassall CH. Reyle K. Biochem. J.  1955,  60:  334 
    Google Scholar
  • 22b Fowden L. Pratt HM. Phytochemistry  1973,  12:  1677 
    Google Scholar
  • 22c Baldwin JE. Adlington RM. Bebbington D. Russel AT. Tetrahedron  1994,  50:  12015 
    Google Scholar
  • 22d For the methylenecyclopropyl glycine see: Grey DO. Fowden L. Biochem. J.  1962,  82:  385 
    Google Scholar
  • 22e See also: Kurokawa N. Ohfune Y. Tetrahedron Lett.  1985,  26:  83 
    Google Scholar
  • 22f For the amphimic acids A and B see: Nemoto T. Ojika M. Sakagami Y. Tetrahedron Lett.  1997,  38:  5667 ; and ref. 23b
    Google Scholar
  • 22g For a cyclopropylidene unit present in a quinoline derivative, isolated from the fermentation broth of Cytophaga Johnsonii, that has antibiotic activity against a few bacteria see: Evans JR. Napier EJ. Fletton RA. J. Antibiot.  1978,  31:  952 
    Google Scholar
  • For some examples see:
  • 23a Salaun J. Bennani F. Compain JC. Fadel A. Ollivier J. J. Org. Chem.  1980,  45:  4129 
    Google Scholar
  • 23b Cohen T. Sherbine JP. Matz JR. Hutchins RR. McHenry BM. Willey PR. J. Am. Chem. Soc.  1984,  106:  3245 
    Google Scholar
  • 23c Meijs GF. Eichinger PCH. Tetrahedron Lett.  1987,  28:  5559 
    Google Scholar
  • 23d Liu H. Shook CA. Jamison JA. Thiruvazhi M. Cohe T. J. Am. Chem. Soc.  1998,  120:  605 
    Google Scholar
  • 23e Katritzky AR. Du W. Levell JR. Li J. J. Org. Chem.  1998,  63:  6710 
    Google Scholar
  • 23f Nemoto T. Yoshino G. Ojika M. Sakagami Y. Tetrahedron  1997,  53:  16669 
    Google Scholar
  • 24 Bernard AM. Frongia A. Piras PP. Synth. Commun.  2003,  33:  801 
    CrossrefGoogle Scholar
  • 25a Julia M. Paris J.-M. Tetrahedron Lett.  1973,  4833 
    CrossrefGoogle Scholar
  • 25b Kocienski PP. Lythgoe B. Ruston SJ. J. Chem. Soc., Perkin Trans. 1  1978,  829 
    CrossrefGoogle Scholar
  • 25c Simpkins NS. Sulphones in Organic Synthesis   Pergamon; Oxford: 1993.  p.254-262  
    CrossrefGoogle Scholar
  • 26 Satoh T. Hanaki N. Yamada N. Asano T. Tetrahedron  2000,  56:  6223 
    CrossrefGoogle Scholar
  • 28 Cyclopropylphenyl sulfide is a rather expensive commercial product, which can be conveniently prepared using cheap starting materials: Tanaka K. Uneme H. Matsui S. Kaji A. Bull. Chem. Soc. Jpn.  1982,  55:  2965 
    Google Scholar
  • 29a Salaun J. Hanack M. J. Org.Chem.  1975,  40:  1994 
    Google Scholar
  • 29b Halazy S. Dumont W. Krief A. Tetrahedron Lett.  1981,  22:  4737 
    Google Scholar
  • 29c Krief A. Ronvaux A. Tuch A. Bull. Soc. Chim. Belg.  1997,  106:  699 
    Google Scholar
  • For a more efficient preparation of the alkylidene-cyclopropane 7c see:
  • 30a Zefirov NS. Kozhushkov SI. Kuznetsova TS. Lukin KA. Kazimirchik IV. J. Org. Chem. USSR (Engl. Transl.)  1988,  24:  605 
    CrossrefGoogle Scholar
  • 30b Meagher TP. Yet L. Hsiao C.-N. Shechter H. J. Org. Chem.  1998,  63:  4181 
    CrossrefGoogle Scholar
27

Typical Procedure for the Reductive Elimination of the Sulfones with Na/Hg.
To a stirred suspension of sodium amalgam (10%, 422 mg, 1.85 mmol) in THF (6 mL) and MeOH (2 mL) at -20 °C, under Argon was added a solution of the appropriate cyclopropylsulfone (0.37 mmol) in THF (2 mL). After 30 min at same temperature the reaction mixture was diluted with Et2O, washed with brine, dried and concentrated in vacuo. Chromatography with light petroleum-Et2O, (1:1) yielded the corresponding alkylidenecyclopropanes.
Typical Procedure for the Reductive Elimination of the Sulfones with Mg/HgCl 2 cat.
A mixture of the cyclopropylsulfone (0.76 mmol), Mg powder (54.7 mg, 2.28 mmol) and few crystals of HgCl2 in dry EtOH (10 mL) was stirred for 1 h at r.t. The reaction mixture was then poured into cold 0.5 N HCl and extracted with Et2O. The organic layer was washed with sat. aq NaHCO3, dried (Na2SO4), filtered and then concentrated in vacuo to give the crude products which were purified as above.
Typical Procedure for the Reductive Elimination of the Sulfoxides with n -BuLi.
To a solution of n-BuLi (1.5 M in hexane, 1.6 mL, 2.4 mmol) at -78 °C, under an argon atmosphere, a solution of the cyclopropylsulfoxide (0.6 mmol) in THF (10 mL) was added dropwise with stirring. After stirring for 5 min, the reaction was quenched with sat. aq NH4Cl and the mixture was extracted with Et2O. The organic layer, dried and evaporated, gave the corresponding alkylidenecyclo-propanes that were purified as above.
All new compounds have been fully characterized by 1H NMR (300 MHz), 13C NMR (75.4 MHz), IR, GLC mass spectra (70 eV) and elemental analyses.
Selected analytical data for some representative derivatives are reported.
Cyclopropyl carbinol 1d: A 65:35 mixture of two diastereoisomers. Minor isomer. White crystals, mp 58-60 °C. Yield: 21%. [α]D 25 +39.30 (c 3.89, CHCl3). IR (film): 3400 cm-1.1H NMR (CDCl3): δ = 0.91-1.30 (m, 4 H), 1.34 (s, 3 H), 1.39 (s, 3 H), 2.62 (br s, 1 H), 3.49 (d, 1 H, J = 5.1 Hz), 3.78 (t, 1 H, J = 8.1 Hz), 4.04 (dd, 1 H, J = 8.1 Hz and 6.6 Hz), 4.43 (q, 1 H, J = 6.6 Hz), 7.12-7.46 (m, 5 H). 13C NMR (CDCl3): δ = 11.3, 13.9, 25.2, 26.4, 26.8, 66.8, 73.4, 77.5, 109.1, 125.7, 128.1, 128.7, 136.1. MS: m/z (%) = 280 (13) [M+], 265 (15), 207(10), 191 (13), 178 (14), 149 (13), 101(100), 91(16). Anal. Calcd for C15H20O3S: C, 64.26; H, 7.19; S, 11.43. Found: C, 64.41; H, 7.26; S, 11.39. Major isomer. Yellow oil. Yield 40%. [α]D 27 -25.74 (c 4.00, CHCl3). IR (neat): 3430 cm-1. 1H NMR (CDCl3): δ = 0.93-1.28 (m, 4 H), 1.31 (s, 3 H), 1.38 (s, 3 H), 2.65 (br s, 1 H), 3.51 (d, 1 H, J = 5.7 Hz), 3.91 (dd, 1 H, J = 6.3 Hz and J = 8.4 Hz), 4.04 (dd, 1 H, J = 8.4 Hz and 6.3 Hz), 4.31 (q, 1 H, J = 6.3 Hz), 7.12-7.48 (m, 5 H). 13C NMR (CDCl3): δ = 13.3, 13.6, 25.1, 26.1, 27.3, 65.5, 75.0, 78.7, 108.5, 125.6, 128.1, 128.5, 136.0. MS: m/z (%) = 280 (14) [M+], 265 (20), 204 (4), 191(23), 179 (20), 149 (14), 101(100), 91(15). Anal. Calcd for C15H20O3S: C, 64.26; H, 7.19; S, 11.43. Found: C, 64.36; H, 7.28; S, 11.34.
Sulfoxide 8d: (Obtained by oxidation of the minor isomer of 1d): Colorless oil. Yield 90%. Spectral data refer to a 70:30 mixture of two inseparable diastereoisomers. IR (neat): 1040, 3430 cm-1. 1H NMR (CDCl3): δ = 0.98 (s, 3 H), 1.18-1.57 (m, 8 H), 1.22 (s, 3 H), 1.27 (s, 3 H), 1.43 (s, 3 H), 1.84 (s, 2 H), 3.64-4.29 (m, 8 H), 7.51-7.70 (m, 10 H). Major isomer: MS: m/z (%) = 281 (39) [M+ - 15], 221 (18), 195 (100), 153 (77), 125 (34), 109 (18), 101(59), 95 (64), 77 (25). Minor isomer: MS: m/z (%) = 281 (34) [M+ - 15], 221 (18), 195 (100), 153 (77), 125 (40), 109 (21), 101 (86), 95 (98), 77 (30). Anal. Calcd for C15H20O4S: C, 60.79; H, 6.80; S, 10.82. Found: C, 60.64; H, 6.68; S, 10.61.
Acetate 9d: Yield 90%. A 70:30 mixture of two inseparable diastereoisomers: IR (neat): 1060, 1740 cm-1. Major isomer: 1H NMR (CDCl3): δ = 1.20-1.36 (m, 4 H), 1.30 (s, 3 H,), 1.34 (s, 3 H), 1.84 (s, 3 H), 3.73 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.07 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.48 (q, 1 H, J = 6.3 Hz), 4.85 (d, 1 H, J = 6.9 Hz), 7.47-7.70 (m, 5 H). Minor isomer: 1H NMR (CDCl3): δ = 1.20-1.36 (m, 4 H), 1.28, (s, 3 H), 1.32 (s, 3 H), 1.83 (s, 3 H), 3.78 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.02 (dd, 1 H, J = 6.3 Hz and J = 8.7 Hz), 4.39 (q, 1 H, J = 6.3 Hz), 5.03 (d, 1 H, J = 6.3 Hz), 7.47-7.70 (m, 5 H). MS (identical for the two isomers): m/z (%) = 323 (7) [M+ - 15], 281 (6), 207 (43), 191 (12), 153 (27), 125 (13), 95 (59), 43 (100). Anal. Calcd for C17H22O5S: C, 60.34; H, 6.55; S, 9.47. Found: C, 60.44; H, 6.78; S, 9.61.
Methylcyclopropilidene 15b: Colorless oil. Yield 65%. Data worked out from the unseparable 60:40 E/Z-mixture: 1H NMR (CDCl3): δ = 1.05-1.12 (m, 2 H), 1.63-1.70 (m, 2 H), 1.76-1.80 (m, 3 H, E-isomer), 1.84-1.89 (m, 3 H, Z-isomer), 2.29 (s, 3 H, Z-isomer), 2.30 (s, 3 H, E-isomer), 2.52-2.55 (m, 2 H), 5.91-5.95 (m, 2 H), 6.98-7.08 (m, 8 H). 13C NMR (CDCl3): δ = 13.3, 15.0, 16.8, 17.0, 19.2, 19.7, 19.8, 20.9, 21.0, 114.3, 114.5, 126.1, 126.3, 128.9, 129.0, 135.0, 135.1, 139.2, 139.5. MS (identical for the two isomers): m/z (%) = 158 (12) [M+], 143 (100), 128 (65), 115 (25), 91 (7), 77 (12). Anal. Calcd for C12H14: C, 91.08; H, 8.92. Found: C, 91.15; H, 8.98.
Compound 16b: A 50:50 mixture of two E-diastereoisomers (syn + anti). Colorless oil. Yield 20%. IR (neat): 3400 cm-1. anti-Diastereoisomer: 1H NMR (CDCl3): δ = 0.85-0.90 (m, 2 H), 1.24-1.26 (m, 1 H), 1.34 (d, 3 H, J = 5.7 Hz), 1.57 (br s, 1 H), 1.75-1.78 (m, 1 H), 2.30 (s, 3 H), 3.36 (q, 1 H, J = 5.7 Hz), 6.95-7.08 (m, 4 H). 13C NMR (CDCl3): δ = 13.6, 20.9, 22.7, 30.6, 71.9, 76.6, 125.8, 129.0, 135.2, 139.3. syn-Diastereoisomer: 1H NMR (CDCl3): δ = 0.91-0.98 (m, 2 H), 1.20-1.22 (m, 1 H), 1.32 (d, 3 H, J = 5.7 Hz), 1.57 (br s, 1 H), 1.84-1.92 (m, 1 H), 2.30 (s, 3 H), 3.34 (q, 1 H, J = 5.7 Hz), 6.95-7.08 (m, 4 H). 13C NMR (CDCl3): δ = 13.1, 20.4, 22.3, 30.6, 71.9, 76.6, 125.7, 129.0, 135.1, 139.4. MS (identical for the two isomers): m/z (%) = 176 (5) [M+], 143 (21), 131 (40), 121 (96), 117 (100), 91 (55), 77 (20). Anal. Calcd for C12H16O: C, 81.77; H, 9.15. Found: C, 81.65; H, 8.86.