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

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.

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

References and Notes

1 For a recent review of Claisen rearrangement, see: Castro MM. Chem. Rev.  2004,  104:  2939 

2 For a pioneering study on the synthesis of spirocycles by Claisen rearrangement of bicyclic dihydropyrans, see: Ireland RE. Aristoff PA. J. Org. Chem.  1979,  44:  4323 

3a Nakazaki A. Miyamoto H. Henmi K. Kobayashi S. Synlett  2005,  1417 

3b Miyamoto H. Okawa Y. Nakazaki A. Kobayashi S. Angew. Chem. Int. Ed.  2006,  45:  2274 

3c Nakazaki A. Kobayashi S. J. Synth. Org. Chem., Jpn.  2008,  66:  124 

For the synthesis of spirocyclic sesquiterpenes, see:

4a Nakazaki A. Era T. Numada Y. Kobayashi S. Tetrahedron  2006,  62:  6264 

4b Nakazaki A. Era T. Kobayashi S. Chem. Lett.  2008,  37:  770 

For the synthesis of pyrrolidinoindoline alkaloids, see:

4c Miyamoto H. Okawa Y. Nakazaki A. Kobayashi S. Tetrahedron Lett.  2007,  48:  1805 

4d

Hirano T., Iwakiri K., Miyamoto H., Nakazaki A., Kobayashi S.; Heterocycles; 2009, 79, 805

5a Büchi G. Powell JE. J. Am. Chem. Soc.  1970,  92:  3126 

For recent examples, see:

5b Ko H. Kim E. Park JE. Kim D. Kim S. J. Org. Chem.  2004,  69:  112 

5c Ilardi EA. Isaacman MJ. Qin Y.-c. Shelly SA. Zakarian A. Tetrahedron  2009,  65:  3261 

6 For a review, see: Sinclair A. Stockman RA. Nat. Prod. Rep.  2007,  24:  298 

7a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  16:  4467 

7b Zhang Y. Herndon JW. Org. Lett.  2003,  5:  2043 

8 Piers E. Wong T. Coish PD. Rogers C. Can. J. Chem.  1994,  72:  1816 

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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.