PDF herunterladen
Synlett 2006(10): 1583-1585  
DOI: 10.1055/s-2006-941603
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel Synthesis of Bicyclo[3.3.0]octane Ring System via a Desymmetric C-H Insertion Reaction

Toshiyuki Kan*a, Tohru Inoueb, Yuichiro Kawamotob, Mitsuhiro Yoneharab, Tohru Fukuyama*b
a School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka-shi 422-8526, Japan
Fax: +81(54)2645747; e-Mail: kant@u-shizuoka-ken.ac.jp;
b Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax: +81(3)58028694; e-Mail: fukuyama@mol.f.u-tokyo.ac.jp;
Weitere Informationen

Publikationsverlauf

Received 1 March 2006
Publikationsdatum:
12. Juni 2006 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

An optically active bicyclo[3.3.0]octane ring was synthesized by an intramolecular C-H insertion reaction. Upon treatment with a catalytic amount of Rh2(S-DOSP)4, a chiral-auxiliary-containing diazoester underwent a C-H insertion reaction to give the desired bicyclo[3.3.0]octane system.

Key words

bicyclo[3.3.0]octane ring - C-H insertion - piperidinyl mandelamide - chiral auxiliary - Rh2(S-DOSP)4

    References and Notes

  • 1 For a review on C-H insertion reactions: Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides   Wiley; New York: 1998. 
  • 2 For a review on asymmetric C-H insertion reactions: Davies HML. Beckwith REJ. Chem. Rev.  2003,  103:  2861 
    CrossrefPubMedSuche in Google Scholar
  • 3 Davies HML. Hansen T. J. Am. Chem. Soc.  1997,  119:  9075 
    CrossrefSuche in Google Scholar
  • 4a Kurosawa W. Kobayashi H. Kan T. Fukuyama T. Tetrahedron  2004,  60:  9615 
    Thieme ConnectSuche in Google Scholar
  • 4b Kurosawa W. Kan T. Fukuyama T. J. Am. Chem. Soc.  2003,  125:  8112 
    Thieme ConnectSuche in Google Scholar
  • 4c Kurosawa W. Kan T. Fukuyama T. Synlett  2003,  1028 
    Thieme Connect
  • 5 For a similar double asymmetric induction in C-H insertion reaction, see: Hashimoto S. Watanabe N. Kawano K. Ikegami S. Synth. Commun.  1994,  24:  3277 
    Suche in Google Scholar
  • 6 Depres JP. Green AE. Org. Synth., Coll. Vol. X  2004,  228 
  • 7 Holmquist CR. Roskamp EJ. J. Org. Chem.  1989,  54:  3258 
    CrossrefSuche in Google Scholar
  • 8 Chiral alcohols 11a and 11b were synthesized from the corresponding lactate and mandelate, respectively. A similar reaction has been reported, see: Devine PN. Dolling U.-H. Heid RM. Tschaen DM. Tetrahedron Lett.  1996,  37:  2683 
    CrossrefSuche in Google Scholar
  • 9 Taber DF. Amedio JC. Patel YK. J. Org. Chem.  1985,  50:  3618 
    CrossrefSuche in Google Scholar
  • 13 Kashihara H. Suemune H. Kawahara T. Sakai K. Tetrahedron Lett.  1987,  28:  6489 
    CrossrefSuche in Google Scholar
  • 14 Watanabe N. Ogawa T. Ohtake Y. Ikegami S. Hashimoto S. Synlett  1996,  85 
    Thieme Connect
  • 15a Watanabe N. Ogawa T. Ohtake Y. Ikegami S. Hashimoto S. Synlett  1996,  85 
  • 15b Hashimoto S. Watanabe N. Ikegami S. Tetrahedron Lett.  1990,  31:  5173 
    Suche in Google Scholar
  • 16 A similar interaction was observed in Rh carbenoid mediated intermolecular cyclopropanation, see: Davies HML. Huby NJS. Cantrell WR. Olive JL. J. Am. Chem. Soc.  1993,  115:  9468 
    CrossrefSuche in Google Scholar
  • 19a For a pentalenolactone, see: Mori K. Tsuji M. Tetrahedron  1988,  44:  2835 
    CrossrefSuche in Google Scholar
  • 19b For a jasmonic acid analogue, see: Toshima H. Nara S. Fujino Y. Ichihara A. Bioscience, Biotechnology, and Biochemistry  2000,  64:  2702 
    CrossrefSuche in Google Scholar
  • For an isocarbacyclin, see:
  • 20a Hashimoto S. Shinoda T. Ikegami S. Chem. Commun.  1988,  1137 
    Thieme Connect
  • 20b Hashimoto S. Miyazaki Y. Ikegami S. Synlett  1996,  324 
    Thieme Connect
10

Initially, we tested a reagent controlled C-H insertion reaction of diazoester 13, which was readily available from 10. Utilizing several chiral rhodium catalysts, the yield and the selectivity of 14 were unsatisfactory as shown in Scheme [3] .

Scheme 3

11

Diastereoselectivity of 5 was determined by the 1H NMR spectra of 15, which was readily converted from 5, as shown in Scheme [4] .

Scheme 4

12

The absolute configuration of 5 was determined as 2R,3R by comparing the optical rotation with that of reported compound 16, see ref. 13. Preparation of 16 from 5 was performed by a decarbonylation reaction (Scheme [5] ).

Scheme 5

17

The C-H insertion 4d reaction with Rh2(OAc)4 proceeded smoothly to afford 5a in 94% yield and a 43% de.

18

Experimental procedure for the C-H insertion reaction of diazoester 4d and confirmation of the diastereoselectivity by conversion of 13a and 13b from 5d are described below.
Compound 5d: to a solution of diazoester 4d (17.5 mg, 0.044 mmol) in CH2Cl2 (0.4 mL) was added Rh2(S-DOSP)4 (8.4 mg, 0.0044 mmol, 10 mol%) at r.t. After stirring for 5 min at the same temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by preparative TLC (50% EtOAc in hexane) to afford 5d (8.9 mg, 0.023 mmol, 55%, 78% de) as a yellow oil and mixture of diastereomers and their enols. IR (film): 2937, 2858, 1755, 1726, 1657, 1446, 1398, 1352, 1230, 1161, 1005, 852 cm-1. 1H NMR (400 MHz, CDCl3): δ = 10.3 (br, 0.2 H), 10.2 (br, 0.04 H), 7.48-7.32 (m, 5 H), 6.42 (s, 0.4 H), 6.24 (s, 0.6 H), 5.77-5.59 (m, 2 H), 3.83-3.13 (m, 7 H), 2.78-2.68 (m, 2 H), 2.22-2.05 (m, 2 H), 1.44-1.27 (m, 5 H), 1.06-1.04 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 216.3, 169.3, 166.8, 166.6, 165.8, 164.0, 135.0, 134.2, 132.8, 131.7, 129.6, 129.4, 129.3, 128.7, 128.6, 128.5, 127.7, 103.1, 75.4, 74.6, 73.0, 59.6, 59.0, 53.3, 51.7, 46.7, 45.3, 43.9, 41.1, 40.6, 40.3, 36.4, 34.7. HRMS (FAB): m/z calcd for C22H26NO4 [MH+]: 368.1861; found: 368.1858 [MH+].
Compounds 15a and 15b: to a solution of 5d (8.9 mg, 0.023 mmol) in THF (0.3 mL) was added NaHMDS in THF (34 µL, 0.034 mmol, 1.5 equiv) at 0 °C. After stirring for 30 min at the same temperature, BOMCl (5.0 µL, 0.035 mmol, 1.5 equiv) was added. After stirring for 30 min, the reaction mixture was quenched by sat. aq NH4Cl, extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by preparative TLC (50% EtOAc in hexane) to afford 15a (4.9 mg, 0.010 mmol, 44 %) as a colorless oil and its isomer 15b (0.6 mg, 0.0012 mmol, 5%) as a colorless oil.
Analytical Data for Compound 15a.
[α]D 21 +94.2 (c 0.165, CHCl3). IR (neat film): 2937, 2856, 1708, 1657, 1450, 1378, 1217, 1144, 1016 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.50-7.28 (m, 10 H), 6.41 (s, 1 H), 5.79 (dd, J = 5.6, 2.3 Hz, 1 H), 5.58 (dd, J = 5.6, 2.0 Hz, 1 H), 5.15 (d, J = 4.3 Hz, 2 H), 4.66 (s, 2 H), 4.07 (dd, J = 8.2, 2.0 Hz, 1 H), 3.62 (m, 1 H), 3.49-3.41 (m, 3 H), 3.03 (dd, J = 18.0, 9.9 Hz, 1 H), 2.91 (m, 1 H), 2.68 (m, 1 H), 2.45 (ddd, J = 17.4, 4.7, 2.1 Hz, 1 H), 2.10 (m, 1 H) 1.54-1.45 (m, 5 H), 1.16 (m, 1 H), 13C NMR (700 MHz, CDCl3): δ = 167.8, 166.8, 164.0, 146.0, 140.9, 137.2, 135.7, 133.5, 129.2, 129.0, 128.9, 128.6, 128.5, 128.3, 128.2, 127.7, 109.1, 92.8, 72.7, 71.9, 54.5, 43.8, 42.3, 40.8, 39.2, 34.7, 29.7, 25.7, 24.7, 24.2. HRMS-FAB: m/z calcd for C30H34NO5 [MH+]: 488.2437; found: 488.2445 [MH+].
Analytical Data for Compound 15b. [α]D 22 +15.3 (c 0.090, CHCl3). IR (neat film): 2935, 1709, 1654, 1454, 1215, 1018 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.52-7.28 (m, 10 H), 6.42 (s, 1 H), 6.18 (dd, J = 5.7, 2.3 Hz, 1 H), 5.66 (dd, J = 5.7, 2.1 Hz, 1 H), 5.12 (s, 2 H), 4.65 (s, 2 H), 3.98 (dd, J = 8.2, 2.0 Hz, 1 H), 3.61-3.39 (m, 4 H), 3.03 (dd, J = 18.3, 9.8 Hz, 1 H), 2.88 (m, 1 H), 2.67 (m, 1 H), 2.50 (m, 1 H), 2.10 (m, 1 H), 1.54-1.45 (m, 5 H), 1.16 (m, 1 H), 13C NMR (100 MHz, CDCl3): δ = 167.3, 166.7, 163.7, 157.1, 136.9, 135.5, 133.3, 128.8, 128.7, 128.4, 128.2, 128.1, 111.3, 92.6, 72.2, 70.3, 54.4, 46.3, 43.3, 40.6, 39.0, 34.3, 25.4, 24.5, 24.0. HRMS-FAB: m/z calcd for C30H34NO5 [MH+]: 488.2437; found: 488.2428 [MH+].