Subscribe to RSS
DOI: 10.1055/s-2005-868520
Stereoselective Synthesis of Functionalized Spiro[4.5]decanes by Claisen Rearrangement of Bicyclic Dihydropyrans
Publication History
Publication Date:
02 May 2005 (online)
![](https://www.thieme-connect.de/media/synlett/200509/lookinside/thumbnails/10.1055-s-2005-868520-1.jpg)
Abstract
A functionalized spiro[4.5]decane framework was synthesized by the Claisen rearrangement of 4-substituted bicyclic dihydropyrans in a highly stereoselective fashion.
Key words
pericyclic reactions - rearrangements - spiro compounds - stereoselective synthesis - terpenoids
- 2 For a recent example of stereoselective synthesis of spiro[4.5]decane framework, see:
Maulide N.Vanherck J.-C.Markò IE. Eur. J. Org. Chem. 2004, 3962 ; and references therein - 3
Katsui N.Matsunaga A.Kitahara H.Yagihashi F.Murai A.Masamune T.Sato N. Bull. Chem. Soc. Jpn. 1977, 50: 1217 ; and references therein - 4
Abe F.Chen R.-F.Yamauchi T. Phytochemistry 1991, 30: 3379 - For reviews on the synthesis of spirocyclic compounds, see:
-
5a
Sannigrahi M. Tetrahedron 1999, 55: 9007 -
5b
Krapcho AP. Synthesis 1974, 383 - For reviews on the Claisen rearrangement, see:
-
6a
Rhoads SJ.Rawlins NR. Org. React. 1975, 22: 1 -
6b
Ziegler FE. Chem. Rev. 1988, 88: 1423 -
6c
Wipf P. In Comprehensive Organic Synthesis Vol. 5:Trost BM.Fleming I.Heathcock CH. Pergamon; Oxford: 1991. p.827 -
6d
Enders D.Knopp M.Schiffers R. Tetrahedron: Asymmetry 1996, 7: 1847 -
6e
Ito H.Taguchi T. Chem. Soc. Rev. 1999, 28: 43 -
6f
Chai Y.Hong S.-P.Lindsay HA.McFarland C.McIntosh MC. Tetrahedron 2002, 58: 2905 -
6g
Hieremann M.Abraham L. Eur. J. Org. Chem. 2002, 1461 -
6h
Martin Castro AM. Chem. Rev. 2004, 104: 2939 - For examples of synthesis of spiro[4.5]decanes by Claisen rearrangement of bicyclic dihydropyrans without a high-oxidation state group in 4-position, see:
-
7a
Ireland RE.Aristoff PA. J. Org. Chem. 1979, 44: 4323 -
7b
Shishido K.Hiroya K.Fukumoto K.Kametani T. Tetrahedron Lett. 1986, 27: 971 -
7c
Brugnolotti M.Corsico CodaA.Desimoni C.Faita G.Gamba Invernizzi A.Righetti PP.Tacconi G. Tetrahedron 1988, 44: 5229 -
7d
Desimoni G.Faita G.Gamba A.Righetti PP.Tacconi G.Toma L. Tetrahedron 1990, 46: 2165 - 9
Collins I.Nadin A.Holmes AB.Long ME.Man J.Baker R. J. Chem. Soc., Perkin Trans. 1 1994, 2205 - 10
Dess DB.Martin JC. J. Am. Chem. Soc. 1991, 113: 7277 - 11
Luche J.-L.Rodriguez-Hahn L.Carabbé P. J. Chem. Soc., Chem. Commun. 1978, 601 - 12 The relative stereochemistry shown for 5a was not determined at this point, however, this stereochemistry was predicted from the results of the nucleophilic addition to the carbonyl group in simple 6-substituted dihydropyrones. For example of methylation, see:
Trost BM.Gunzner JL.Dirat O.Rhee YH. J. Am. Chem. Soc. 2002, 124: 10396 ; this prediction is also supported by the stereochemistry of 12 derived from rearrangement product 11 -
13a
Earnshaw C.Wallis CJ.Warren S. J. Chem. Soc., Perkin Trans. 1 1979, 3099 -
13b
Patel D.Schmidt RJ.Gordon EM. J. Org. Chem. 1992, 57: 7143 - For recent reviews on microwave-assisted organic synthesis, see:
-
14a
Lidström P.Tierney J.Wathey B.Westman J. Tetrahedron 2001, 57: 9225 -
14b
Perreux L.Loupy A. Tetrahedron 2001, 57: 9199 - 15 For a review on Lewis acid catalyzed Claisen rearrangement, see:
Lutz RP. Chem. Rev. 1984, 84: 205 - 16
Takai K.Mori I.Oshima K.Nozaki H. Bull. Chem. Soc. Jpn. 1984, 57: 446 - For examples of palladium-catalyzed Claisen rearrangement, see:
-
17a
Bann JL.Bickelhaupt F. Tetrahedron Lett. 1986, 27: 6267 -
17b
Mikami K.Takahashi K.Nakai T. Tetrahedron Lett. 1987, 28: 5879 -
17c For a review on mercury(II)- or palladium(II)-catalyzed Claisen rearrangement, see:
Overman LE. Angew. Chem., Int. Ed. Engl. 1984, 23: 579 - 18
Büchi G.Powell JE. J. Am. Chem. Soc. 1970, 92: 3126 - 21 For a related example, see:
Kang H.-J.Paquette LA. J. Am. Chem. Soc. 1990, 112: 3252 -
22a
Borowitz IJ.Gonis G. Tetrahedron Lett. 1964, 1151 -
22b
Borowitz IJ.Gonis G.Kelsey R.Rapp R.Williams GJ. J. Org. Chem. 1966, 31: 3032
References
Visiting scientist from Sankyo Co., Ltd.
8All new compounds were fully characterized by 1H NMR and 13C NMR, IR and mass spectra. Data for the selected compounds follow.
Compound 4: R
f
= 0.38 (hexane-EtOAc = 75:25). 1H NMR (300 MHz, CDCl3): δ = 5.88 (dq, J = 15.4, 6.4 Hz, 1 H), 5.66 (ddq, J = 15.4, 7.2, 1.5 Hz, 1 H), 4.88 (ddd, J = 12.5, 7.2, 4.3 Hz, 1 H), 2.60-2.50 (m, 5 H), 2.41 (dd, J = 16.9, 4.1 Hz, 1 H), 1.92 (quint., J = 7.5 Hz, 2 H), 1.77 (dd, J = 6.4, 1.5 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 189.74, 178.39, 131.37, 127.79, 114.01, 81.57, 40.87, 32.73, 25.43, 19.11, 17.73. IR (neat): 1779, 1666, 1613, 1426, 1154, 965 cm-1. HRMS (EI): m/z calcd for C11H14O2: 178.0994; found: 178.0987.
Compound 5b (>95% dr by 1H NMR analysis): R
f
= 0.56 (hexane-EtOAc = 90:10). 1H NMR (300 MHz, CDCl3): δ = 5.70 (dq, J = 15.3, 6.2 Hz, 1 H), 5.55 (dd, J = 15.3, 7.3 Hz, 1 H), 4.38-4.27 (m, 2 H), 2.42-2.08 (m, 5 H), 1.94 (ddd, J = 13.4, 6.5, 2.2 Hz, 1 H), 1.81-1.72 (m, 2 H), 1.63 (d, J = 6.2 Hz, 3 H), 0.82 (s, 9 H), 0.00 (s, 3 H), -0.01 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 153.00, 130.39, 128.96, 110.59, 77.37, 64.69, 38.81, 31.37, 28.90, 25.80, 19.18, 18.24, 17.71, -4.61, -4.88. IR (neat): 1686 cm-1. HRMS (ESI): m/z calcd for C17H30O2NaSi: 317.1907; found: 317.1897.
Compound 9 (>95% dr by 1H NMR analysis): R
f
= 0.52 (hexane-EtOAc = 75:25). 1H NMR (400 MHz, CDCl3): δ = 5.73 (ddt, J = 9.8, 4.0, 2.9 Hz, 1 H), 5.61 (dq, J = 9.8, 2.9 Hz, 1 H), 3.17 (dq, J = 20.8, 2.9 Hz, 1 H), 2.86-2.73 (m, 2 H), 2.61-2.57 (m, 1 H), 2.36-2.29 (m, 1 H), 2.24-2.15 (m, 1 H), 2.01-1.80 (m, 3 H), 1.12 (d, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 214.01, 204.38, 131.05, 122.54, 68.28, 41.40, 40.64, 37.99, 30.98, 19.82, 16.19. IR (neat): 1737, 1704 cm-1. HRMS (ESI): m/z calcd for C11H14O2Na: 201.0886; found: 201.0889.
Compound 11 (>95% dr by 1H NMR analysis): R
f
= 0.51 (hexane-EtOAc = 90:10). 1H NMR (400 MHz, CDCl3): δ = 5.52-5.40 (m, 2 H), 4.13 (dd, J = 9.5, 6.1 Hz, 1 H), 2.27-2.20 (m, 4 H), 2.06-1.87 (m, 3 H), 1.81-1.62 (m, 2 H), 0.89 (d, J = 7.4 Hz, 3 H), 0.78 (s, 9 H), 0.00 (s, 3 H), -0.03 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 220.52, 131.07, 123.14, 66.03, 56.41, 39.95, 37.20, 33.17, 29.10, 25.80, 18.69, 17.94, 17.59, -4.13, -5.26. IR (neat): 1734 cm-1. HRMS (ESI): m/z calcd for C17H30O2NaSi: 317.1907; found: 317.1903.
Compound 12 (>95% dr by 1H NMR analysis): R
f
= 0.81 (hexane-EtOAc = 75:25). 1H NMR (400 MHz, CDCl3): δ = 5.64-5.48 (m, 2 H), 4.21 (d, J = 3.7 Hz, 1 H), 4.17 (dd, J = 5.6, 4.4 Hz, 1 H), 2.20-1.63 (m, 7 H), 1.49 (s, 3 H), 1.38 (s, 3 H), 1.35-1.25 (m, 2 H), 0.98 (d, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 131.89, 123.29, 97.55, 74.81, 64.26, 46.54, 36.48, 30.34, 30.12, 30.10, 26.07, 19.89, 19.51, 15.43. IR (neat): 1092 cm-1. HRMS (ESI): m/z calcd for C14H22O2Na: 245.1512; found: 245.1500.
Compound 14 (67% dr by 1H NMR analysis): R
f
= 0.42 and 0.34 (hexane-EtOAc = 90:10). 1H NMR (400 MHz, CDCl3): δ = 5.94 (dt, J = 5.2, 1.6 Hz, 1 H), 5.77 (ddt, J = 9.6, 5.2, 2.0 Hz, 0.33 H), 5.68 (ddt, J = 9.6, 0.8, 3.6 Hz, 0.33 H), 5.64-5.57 (m, 1.33 H), 3.59 (s, 2 H), 3.42 (s, 1 H), 2.94 (br d, J = 20.4 Hz, 0.67 H), 2.71-2.64 (m, 1.33 H), 2.48 (ddq, J = 18.0, 1.2, 5.2 Hz, 0.33 H), 2.37-2.05 (m, 4.33 H), 1.94-1.68 (m, 2.33 H), 1.12 (d, J = 6.8 Hz, 1 H), 1.00 (d, J = 7.2 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 219.53, 218.52, 142.51, 142.34, 133.27, 131.07, 124.79, 124.11, 114.79, 111.26, 59.60, 58.99, 54.87, 53.57, 39.70, 38.56, 37.28, 37.19, 36.93, 36.04, 27.28, 23.23, 18.97, 18.51, 16.55, 16.47. IR (neat): 2961, 1732, 1670, 1222, 1128 cm-1. HRMS (EI): m/z calcd for C13H18O2: 206.1307; found: 206.1306.
Compound 16 (52% dr by 1H NMR analysis): R
f
= 0.30 and 0.21 (hexane-EtOAc = 75:25). 1H NMR (400 MHz, CDCl3): δ = 9.74 (s, 0.48 H), 9.57 (s, 0.52 H), 5.77-5.58 (m, 2 H), 4.01 (br s, 0.52 H), 3.78 (br s, 0.48 H), 2.72-2.57 (m, 1 H), 2.48-1.78 (m, 8 H), 1.09 (d, J = 7.3 Hz, 1.56 H), 1.03 (d, J = 7.6 Hz, 1.44 H). 13C NMR (100 MHz, CDCl3): δ = 219.53, 202.31, 201.53, 130.95 130.88, 122.35, 121.56, 79.47, 78.78, 58.49, 53.68, 40.33, 39.92, 38.86, 37.44, 32.42, 31.91, 30.99, 19.91, 19.06, 17.39, 16.42. IR (neat): 3471, 1730 cm-1. HRMS (ESI): m/z calcd for C12H16O3Na: 231.0991; found: 231.0986.
Under the thermal condition at lower temperature (165 °C), no formation of spiro[4.5]decane 11 was observed.
20Experimental Procedure. A solution of 5b (109 mg, >95% dr) in dry toluene (3.7 mL) was heated at 250 °C for 11 h in a sealed tube. The resulting mixture was cooled to r.t. and concentrated. Purification by silica gel column chromatography (hexane-EtOAc = 98:2) gave 75 mg (69% yield, >95% dr by 1H NMR analysis) of 11 as a colorless clear oil.