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

Toshiyuki Kan; Tohru Inoue; Yuichiro Kawamoto; Mitsuhiro Yonehara; Tohru Fukuyama

doi:10.1055/s-2006-941603

LETTER

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

Toshiyuki Kan*^a, Tohru Inoue^b, Yuichiro Kawamoto^b, Mitsuhiro Yonehara^b, 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;

Abstract

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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

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References

References and Notes

<A NAME="RU02206ST-1">1</A> 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.

<A NAME="RU02206ST-2">2</A> For a review on asymmetric C-H insertion reactions: Davies HML. Beckwith REJ. Chem. Rev. 2003, 103: 2861

<A NAME="RU02206ST-3">3</A> Davies HML. Hansen T. J. Am. Chem. Soc. 1997, 119: 9075

<A NAME="RU02206ST-4A">4a</A> Kurosawa W. Kobayashi H. Kan T. Fukuyama T. Tetrahedron 2004, 60: 9615

<A NAME="RU02206ST-4B">4b</A> Kurosawa W. Kan T. Fukuyama T. J. Am. Chem. Soc. 2003, 125: 8112

<A NAME="RU02206ST-4C">4c</A> Kurosawa W. Kan T. Fukuyama T. Synlett 2003, 1028

<A NAME="RU02206ST-5">5</A> 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

<A NAME="RU02206ST-6">6</A> Depres JP. Green AE. Org. Synth., Coll. Vol. X 2004, 228

<A NAME="RU02206ST-7">7</A> Holmquist CR. Roskamp EJ. J. Org. Chem. 1989, 54: 3258

<A NAME="RU02206ST-8">8</A> 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

<A NAME="RU02206ST-9">9</A> Taber DF. Amedio JC. Patel YK. J. Org. Chem. 1985, 50: 3618

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

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

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

<A NAME="RU02206ST-13">13</A> Kashihara H. Suemune H. Kawahara T. Sakai K. Tetrahedron Lett. 1987, 28: 6489

<A NAME="RU02206ST-14">14</A> Watanabe N. Ogawa T. Ohtake Y. Ikegami S. Hashimoto S. Synlett 1996, 85

<A NAME="RU02206ST-15A">15a</A> Watanabe N. Ogawa T. Ohtake Y. Ikegami S. Hashimoto S. Synlett 1996, 85

<A NAME="RU02206ST-15B">15b</A> Hashimoto S. Watanabe N. Ikegami S. Tetrahedron Lett. 1990, 31: 5173

<A NAME="RU02206ST-16">16</A> 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

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

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⁺].

<A NAME="RU02206ST-19A">19a</A> For a pentalenolactone, see: Mori K. Tsuji M. Tetrahedron 1988, 44: 2835

<A NAME="RU02206ST-19B">19b</A> For a jasmonic acid analogue, see: Toshima H. Nara S. Fujino Y. Ichihara A. Bioscience, Biotechnology, and Biochemistry 2000, 64: 2702

For an isocarbacyclin, see:

<A NAME="RU02206ST-20A">20a</A> Hashimoto S. Shinoda T. Ikegami S. Chem. Commun. 1988, 1137

<A NAME="RU02206ST-20B">20b</A> Hashimoto S. Miyazaki Y. Ikegami S. Synlett 1996, 324