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Synlett 2009(10): 1605-1608  
DOI: 10.1055/s-0029-1217339
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Claisen Rearrangement Using Bicyclic 2-[(Z)-Alkenyl]dihydropyran: Stereoselective Synthesis of trans-Substituted Spiro[4.5]decane

Atsuo Nakazaki, Susumu Kobayashi*
Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI), 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan
Fax: +81(4)71213671; e-Mail: kobayash@rs.noda.tus.ac.jp;
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Publication History

Received 5 March 2009
Publication Date:
02 June 2009 (online)

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Abstract

We report the first example of the Claisen rearrangement in the 2-[(Z)-alkenyl]dihydropyran system yielding spiro[4.5]decane in a trans fashion. This protocol is useful for the synthesis of trans-substituted spiro[4.5]decanes, a potentially useful class of spirocyclic terpenes and alkaloids.

Key words

2-(alkenyl)dihydropyran - alkynes - Claisen rearrangement - spiro compounds - stereoselective synthesis

    References and Notes

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10

All new compounds were fully characterized by ¹H NMR, ¹³C NMR, and IR analyses. Data for the selected compounds are given below.
Compound 9a (>95% dr by ¹H NMR analysis): R f = 0.65 (hexane-EtOAc = 95:5). ¹H NMR (400 MHz, CDCl3): δ = 6.01 (dd, J = 11.0, 8.1 Hz, 1 H), 5.55 (br d, J = 11.0 Hz, 1 H), 5.01 (br t, J = 10.7 Hz, 1 H), 4.45 (br t, J = 6.6 Hz, 1 H), 2.54-2.07 (m, 8 H), 1.92-1.75 (m, 2 H), 1.54-1.41 (m, 4 H), 0.93 (t, J = 7.3 Hz, 3 H), 0.90 (s, 9 H), 0.08 (s, 3 H), 0.07 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 152.8, 140.1, 111.2, 110.6, 96.9, 76.1, 74.6, 64.3, 37.5, 31.4, 30.8, 29.1, 25.8, 21.9, 19.2, 19.1, 18.2, 13.6, -4.63, -4.91. IR (neat): 2217, 1686, 1463, 1383, 1251, 1065 cm-¹. HRMS (EI): m/z calcd for C22H36O2Si: 360.2485; found: 360.2490.
Compound 9b (>95% dr by ¹H NMR analysis): R f = 0.71 (hexane-EtOAc = 9:1). ¹H NMR (400 MHz, CDCl3): δ = 6.16 (dd, J = 11.0, 8.0 Hz, 1 H), 5.57 (br d, J = 11.0 Hz, 1 H), 5.03 (br t, J = 10.0 Hz, 1 H), 4.42 (br t, J = 6.7 Hz, 1 H), 2.53-2.10 (m, 5 H), 1.89-1.74 (m, 3 H), 0.89 (s, 9 H), 0.21 (s, 9 H), 0.09 (s, 3 H), 0.07 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 152.7, 143.3, 110.9, 110.2, 101.4, 100.5, 74.7, 64.2, 37.3, 31.4, 29.2, 25.9, 19.2, 18.3, -0.01, -4.51, -4.78. IR (neat): 2149, 1686, 1471, 1382, 1251, 1066 cm-¹. ESI-HRMS: m/z calcd for C21H36O2NaSi2: 399.2146; found: 399.2135.

11

General Procedure for the Claisen Rearrangement of 9
A degassed solution of the Claisen precursor 9a (26.3 mg, 0.073 mmol) in triglyme (7.3 mL) was heated at 250 ˚C for 10 min in a sealed tube, washed with a soln of KOH in 2-PrOH before use. The resulting mixture was cooled to r.t. and diluted with H2O. The aqueous layer was extracted two times with EtOAc. The combined organic layer was washed with H2O and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The obtained product was purified by SiO2 column chromatography (hexane-EtOAc = 99:1) giving 10.2 mg of spiro[4.5]decane 10a (39% yield, >95% dr by ¹H NMR analysis).
Compound 10a: R f = 0.63 (hexane-EtOAc = 9:1). ¹H NMR (400 MHz, CDCl3): δ = 5.55-5.43 (m, 2 H), 3.95 (dd, J = 10.1, 6.1 Hz, 1 H), 3.39 (br s, 1 H), 2.27-1.87 (m, 10 H), 1.48-1.31 (m, 4 H), 0.89 (t, J = 7.1 Hz, 3 H), 0.83 (s, 9 H), 0.02 (s, 3 H), -0.03 (s, 3 H). ¹³C NMR (100 MHz, CDCl3):
δ = 223.0, 127.8, 124.5, 82.4, 78.7, 71.7, 56.2, 39.9, 36.4, 32.6, 30.9, 25.7, 25.0, 21.9, 20.0, 18.4, 17.8, 13.6, -4.34, -5.22. IR (neat): 1742, 1461, 1256, 1093 cm-¹. HRMS (EI): m/z calcd for C22H36O2Si: 360.2485; found: 360.2484.
Compound 10b (>95% dr by ¹H NMR analysis): R f = 0.74 (hexane-EtOAc = 9:1). ¹H NMR (400 MHz, CDCl3): δ = 5.58-5.53 (m, 1 H), 5.50-5.46 (m, 1 H), 3.94 (dd, J = 10.0, 6.1 Hz, 1 H), 3.41 (br s, 1 H), 2.31-1.89 (m, 8 H), 0.83 (s, 9 H), 0.12 (s, 9 H), 0.02 (s, 3 H), -0.04 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 222.6, 126.7, 125.1, 105.5, 86.7, 71.5, 56.1, 39.8, 37.4, 32.6, 25.8, 25.0, 20.0, 17.9, -4.31, -5.18.
IR (neat): 2175, 1742, 1471, 1404, 1250, 1065 cm-¹. ESI-HRMS: m/z calcd for C21H36O2NaSi2: 399.2146; found: 399.2144.