Stereoselective Synthesis of Functionalized Spiro[4.5]decanes by Claisen Rearrangement of Bicyclic Dihydropyrans

Abstract

A functionalized spiro[4.5]decane framework was ­synthesized by the Claisen rearrangement of 4-substituted bicyclic dihydropyrans in a highly stereoselective fashion.

pericyclic reactions - rearrangements - spiro compounds - stereoselective synthesis - terpenoids

References

1

Visiting scientist from Sankyo Co., Ltd.

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

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7a Ireland RE. Aristoff PA. J. Org. Chem.  1979,  44:  4323 

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8

All 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.

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 

19

Under the thermal condition at lower temperature (165 °C), no formation of spiro[4.5]decane 11 was observed.

20

Experimental 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.

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