Intramolecular Diels-Alder Reactions with 6-Hydroxypyranone as Dienophile

Frank Richter; Cäcilia Maichle-Mössmer; Martin E. Maier

doi:10.1055/s-2002-32584

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Synlett 2002(7): 1097-1100
DOI: 10.1055/s-2002-32584

LETTER

Intramolecular Diels-Alder Reactions with 6-Hydroxypyranone as Dienophile

Frank Richter^a, Cäcilia Maichle-Mössmer^b, Martin E. Maier*^a
^a Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
^b Institut für Anorganische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
Fax: +49(7071)295137; e-Mail: martin.e.maier@uni-tuebingen.de;

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Publication History

Received 26 March 2002
Publication Date:
07 February 2007 (online)

Abstract
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Abstract

Oxidative rearrangement of furfuryl alcohols carrying an appropriately positioned dienyl side chain provided hydroxypyranone intermediates that underwent a subsequent intramolecular Diels-Alder reaction. The heterocyclic ring of the tricyclic cycloadducts opened via ring chain tautomerism to highly functionalized decalin or hexahydroindene derivatives, respectively. In one instance, that is compound 6 the structure was secured by X-ray analysis.

Key words

furfuryl alcohol - intramolecular Diels-Alder - pyranone - decalin - oxidative rearrangement

References

1 Lipshutz BH. Chem. Rev. 1986, 86: 795

Crossref Google Scholar
2 Maier ME. In Organic Synthesis Highlights Waldmann H. VCH Verlagsgesellschaft mbH; Weinheim: 1995. p.231

Google Scholar
3 Lautens M. Ma S. Chiu P. J. Am. Chem. Soc. 1997, 119: 6478

Google Scholar
4 Sammes PG. Gazz. Chim. Ital. 1986, 116: 109

Google Scholar
5 Martin SF. Guinn DE. J. Org. Chem. 1987, 52: 5588

Crossref Google Scholar
6 Taniguchi T. Nakamura K. Ogasawara K. Synlett 1996, 971

Article in Thieme Connect Google Scholar
7 Archer DA. Bromidge SM. Sammes PG. J. Chem. Soc., Perkin Trans. 1 1988, 3223

Crossref Google Scholar
8 Wender PA. Rice KD. Schnute ME. J. Am. Chem. Soc. 1997, 119: 7897

Crossref Google Scholar
9 Knol J. Jansen JFGA. van Bolhuis F. Feringa BL. Tetrahedron Lett. 1991, 32: 7465

Crossref Google Scholar
10 Kobayashi Y. Okui H. J. Org. Chem. 2000, 65: 612

Crossref Google Scholar
11 Ho T.-L. Sapp SG. Synth. Commun. 1983, 13: 207

Crossref Google Scholar
12 Richter F. Bauer M. Perez C. Maichle-Mössmer C. Maier ME. J. Org. Chem. 2002, 67: 2474

Crossref Google Scholar
13 Dess DB. Martin JC. J. Am. Chem. Soc. 1991, 113: 7277

Crossref Google Scholar
14 Meyer SD. Schreiber SL. J. Org. Chem. 1994, 59: 7549

Crossref Google Scholar
16 Jauch J. Angew. Chem. Int. Ed. 2000, 39: 2764 ; Angew. Chem. 2000, 112, 2874

Google Scholar

15

Experimental Details: (4 E )-1-(2-Furyl)hepta-4,6-dien-1-ol (3). To a cooled (0 °C) solution of furan (2.7 mL, 37 mmol) and 4,4-bipyridyl (10 mg) in THF (30 mL) was added
n-BuLi (8 mL, 2.6 M in hexanes, 21.0 mmol). After stirring at 0 °C for 3 h, the dark-red solution was cooled to -70 °C before the aldehyde 2 (4.1 g, 37.0 mmol), dissolved in THF (20 mL) was added dropwise. The reaction mixture was stirred at -60 °C for 4 h and then poured onto a mixture of Et₂O and aq sat. NH₄Cl. After separation of the phases, the aqueous phase was extracted with Et₂O (3 × 30 mL). The combined organic layers were dried with MgSO₄, filtered and concentrated in vacuo. Flash chromatography (CH₂Cl₂/EtOAc, 8:1) gave the furfuryl alcohol 3 (4.2 g, 75%) as a colorless oil. TLC (CH₂Cl₂/EtOAc, 8:1): R_f = 0.47; ¹H NMR (250 MHz, CDCl₃): δ = 1.93 (dd, J = 7.2, 14.3 Hz, 2 H, H-3), 2.12-2.20 (m, 2 H, H-2), 2.26 (s, 1 H, OH), 4.86 (t, J = 6.7 Hz, 1 H, H-1), 4.96 (d, J = 10.1 Hz, 1 H, H-7cis), 5.09 (d, J = 16.5 Hz, 1 H, H-7trans), 5.68 (dt, J = 7.2, 15.5 Hz, 1 H, H-4), 6.06 (dd, J = 10.4, 15.5 Hz, 1 H, H-5), 6.21 (d, J = 3.4 Hz, 1 H, furan H-3), 6.28-6.34 (m, 2 H, H-6, furan H-4), 7.35 (d, J = 1.5 Hz, 1 H, furan H-5); ¹³C NMR (63 MHz, CDCl₃): δ = 28.42 (C-3), 34.77 (C-2), 67.02 (C-1), 105.86 (furan C-4), 110.07 (furan C-3), 115.15 (C-7), 131.63 (C-5), 133.86 (C-4), 137.02 (C-6), 141.87 (furan C-5), 156.52 (furan C-2); MS (70 eV, EI): m/z (%) = 178(17) [M]⁺, 159(100) [M - H₂O]⁺, 97(100) [M - C₆H₉]⁺, 81(26) [C₆H₉]⁺, 66(20) [C₄H₃O]⁺; HRMS (EI): calcd for C₁₁H₁₄O₂: 178.09563. Found: 178.09938.
(1 S ,4a R ,7 R ,8a R )-7-Hydroxy-8-oxo-1,2,4a,5,6,7,8,8a-octahydronaphthalene-1-carbaldehyde (6). To a solution of the furfuryl alcohol 4 (760 mg, 4.3 mol) and vanadylacetyl acetonate (40 mg, 0.15 mmol) in CH₂Cl₂ (20 mL) was added dropwise at -30 °C tert-butylhydroperoxide (1 mL, 5.5 mmol), dissolved in CH₂Cl₂ (5 mL). The resulting dark-red solution was stirred at 0 °C overnight. The mixture was poured onto H₂O, the organic layer was separated and the aqueous phase extracted with CH₂Cl₂ (3 × 20 mL). The combined organic layers were dried with MgSO₄, filtered, and concentrated in vacuo. In order to remove the catalyst, the residue was filtered through a short column of flash silica gel using CH₂Cl₂ as eluent. After concentration of the organic filtrate, the residue was dissolved in toluene (30 mL), a trace of hydroquinone was added, and the mixture refluxed for 48 h. Thereafter, the toluene was removed in vacuo and the residue purified by flash chromatography (CH₂Cl₂/EtOAc, 8:1) to provide the decalin 6 (389 mg, 47%) as colorless crystals of mp 105 °C. TLC (CH₂Cl₂/EtOAc, 8:1): R_f = 0.25; IR(film): 3444, 2872, 1714, 1260, 1094
cm^-1; ¹H NMR (250 MHz, CDCl₃): δ = 1.53 (ddd, J = 3.5, 12.8, 13.5 Hz, 1 H, H-8ax), 1.89 (dq, J = 3.1, 14.2 Hz, 1 H, H-5ax), 2.05 (tt, J = 4.0, 14.2 Hz, 1 H, H-5eq), 2.19-2.25 (m, 1 H, H-6eq), 2.35-2.38 (m, 1 H, H-4a), 2.39-2.43 (m, 1 H, H-2ax), 2.53-2.59 (m, 1 H, H-2eq), 3.00-3.02 (m, 1 H, H-8a), 3.31-3.34 (m, 1 H, H-1), 3.52 (s, 1 H, OH), 4.08 (ddd, J = 1.3, 12.2, 12.4 Hz, 1 H, H-7), 5.42 (dd, J = 1.7, 10.2 Hz, 1 H, H-4), 5.81 (dq, J = 3.1, 14.2 Hz, 1 H, H-3), 9.81 (s, 1 H, CHO); ¹³C NMR (63 MHz, CDCl₃): δ = 22.51 (C-2), 27.66 (C-5), 31.14 (C-6), 33.38 (C-8a), 45.64 (C-4a), 47.10 (C-1), 75.48 (C-7), 128.29 (C-3), 129.69 (C-4), 203.16 (CHO), 209.36 (C-8); MS (70 eV, EI): m/z (%) = 194(3) [M]⁺, 176(33) [M + H - OH]⁺, 167(27) [M + H - CO]⁺, 149(39) [M - OH - CO]⁺.
(4 E ,6 E )-1-(2-Furyl)-8-[(2-methoxyethoxy)methoxy]-3,3-dimethylocta-4,6-dien-1-ol (9). As described for compound 3, furan (4.4 mL, 60.0 mmol), 4,4-bipyridyl (10 mg) in THF (50 mL), n-BuLi (22 mL, 2.6 M in hexanes, 57.0 mmol), and crude aldehyde 8 (about 20 mmol) [prepared from alcohol 7 by Dess-Martin oxidation], dissolved in THF (10 mL) were converted to alcohol 9 (4.5 g, 71%), slightly yellow oil. TLC (petroleum ether/EtOAc, 7:3): R_f = 0.27; ¹H NMR (250 MHz, CDCl₃): δ = 1.02 (s, 3 H, CH₃), 1.07 (s, 3 H, CH₃), 1.89 (d, J = 6.1 Hz, 2 H, H-2), 2.04 (s, 1 H, OH), 3.37 (s, 3 H, OCH₃), 3.52-3.70 (m, 4 H, OCH₂CH₂O), 4.07 (d, J = 6.4 Hz, 2 H, H-8), 4.70 (s, 2 H, H-1, OCH₂O), 5.60-5.72 (m, 2 H, H-4, H-7), 5.98 (dd, J = 10.1, 15.6 Hz, 1 H, H-5), 6.16 (d, J = 3.2 Hz, 1 H, furan H-3), 6.23 (dd, J = 10.1, 15.0 Hz, 1 H, H-6), 6.27 (dd, J = 1.4, 3.2 Hz, 1 H, furan H-4), 7.32 (d, J = 1.4 Hz, 1 H, furan H-5); ¹³C NMR (63 MHz, CDCl₃): δ [ppm] = 1.02 (CH₃), 28.05 (CH₃), 35.62 (C-3), 48.14 (C-2), 58.92 (OCH₃), 65.52 (C-1), 66.75 (C-8), 67.61 (OCH₂CH₂OMe), 71.74 (CH₂OMe), 94.54 (OCH₂O), 105.55 (furan C-3), 110.12 (furan C-4), 126.07 (C-5), 127.10 (C-7), 133.41 (C-3), 141.63 (C-6), 144.30 (furan C-5), 157.17 (furan C-2); MS (FD): m/z (%) = 324.3(100) [M]⁺, 219.1(34) [M - OMEM]⁺.
(1 S ,2 S ,4a R ,7 R ,8a R )-7-hydroxy-2-{[(2-methoxyethoxy)methoxy]methyl}-5,5-dimethyl-8-oxo-1,2,4a,5,6,7,8,8a-octahydronaphthalene-1-carbaldehyde (12). As described for compound 6, furfuryl alcohol 9 (970 mg, 3.0 mol) was rearranged using vanadylacetyl acetonate (27 mg, 0.10 mmol) in CH₂Cl₂ (10 mL) and tert-butylhydroperoxide (0.8 mL, 3.3 mmol), dissolved in CH₂Cl₂ (5 mL). The crude hydroxypyranone 10 was thermolyzed in toluene (30 mL), containing hydroquinone (about 5 mg) to provide decalin 12 (529 mg, 52%) as colorless oil. TLC (CH₂Cl₂/EtOAc, 2:1): R_f = 0.25; ¹H NMR (250 MHz, CDCl₃) δ = 1.05 (s, 3 H, (CH₃), 1.34 (s, 3 H, (CH₃), 1.54 (dd, J = 12.2, 12.5 Hz, 1 H, H-6ax), 1.98 (ddd, J = 2.7, 7.2, 12.5 Hz, 1 H, H-6eq), 2.19-2.21 (m, 1 H, H-2), 2.75-2.81 (m, 1 H, H-4a), 3.33-3.38 (m, 4 H, H-8a, OCH₃), 3.54-3.57 (m, 2 H, CH₂OMEM), 3.62-3.65 (m, 3 H, CH₂OMEM, OCH₂CH₂O), 3.69-3.73 (m, 2 H, OCH₂CH₂O), 4.23 (dd, J = 7.2, 12.2 Hz, 1 H, H-7), 4.77 (d, J = 2.2 Hz, 2 H, OCH₂O), 5.65 (dt, J = 2.4, 10.3 Hz, 1 H, H-3), 5.71 (dt, J = 2.6, 10.3 Hz, 1 H, H-4), 9.64 (s, 1 H, CHO); ¹³C NMR (63 MHz, CDCl₃) δ = 26.85 (CH₃), 27.46 (CH₃), 33.04 (C-4a), 42.03 (C-1), 43.45 (C-6), 45.43 (C-2), 46.83 (C-8a), 58.96 (OCH₃), 66.93 (OCH₂CH₂OMe), 70.59 (CH₂OMEM), 71.74 (CH₂OMe), 71.92 (C-7), 95.62 (OCH₂O), 126.51 (C-4), 129.17 (C-3), 202.65 (CHO), 210.12 (C-8).
Hemiacetal 11: TLC (CH₂Cl₂/EtOAc, 2:1): R_f = 0.37; ¹H NMR (250 MHz, CDCl₃): δ = 1.08 (s, 3 H, CH₃), 1.12 (s, 3 H, CH₃), 1.89-1.91 (m, 1 H, H-6), 2.03 (d, J = 15.8 Hz, 1 H, H-6ax), 2.45-2.47 (m, 1 H, H-2), 2.50 (d, J = 15.8 Hz, 1 H, H-6eq), 2.69-2.72 (m, 1 H, H-1), 3.36 (m, 4 H, H-1, OCH₃), 3.53-3.55 (m, 2 H, OCH₂CH₂O), 3.64-3.77 (m, 4 H, CH₂OMEM, OCH₂CH₂O), 4.34 (d, J = 7.3 Hz, 1 H, H-7), 4.72 (s, 2 H, OCH₂O), 5.07 (d, J = 3.5 Hz, 1 H, OCHOH), 5.81 (d, J = 9.4 Hz, 1 H, H-3), 5.99 (d, J = 9.4 Hz, 1 H, H-4); ¹³C NMR (63 MHz, CDCl₃): δ = 28.16 (CH₃), 28.72 (CH₃), 29.73 (C-5), 35.74 (C-2), 41.40 (C-4a), 44.35 (C-8a), 47.57 (C-6), 49.73 (C-1), 58.99 (OCH₃), 66.83 (OCH₂CH₂OMe), 68.91 (CH₂OMEM), 71.80 (CH₂OMe), 78.71 (C-7), 95.55 (OCH₂O), 101.15 (OCHOH), 130.29 (C-3), 131.23 (C-4), 208.58 (C-8); IR(film): 2958, 2932, 2877, 1720, 1115, 1044 cm^-1; MS (FD): m/z (%) = 340.4(100) [M]⁺, 232.2(84) [M - OH]⁺, 235.0(16) [M - OMEM]⁺.
(3 E ,5 E )-1-(2-Furyl)-7-[(2-methoxyethoxy)methoxy]-2,2-dimethylhepta-3,5-dien-1-ol (15). As described for compound 3, furan (1.1 mL, 15.0 mmol), 4,4-bipyridyl (10 mg) in THF (30 mL), n-BuLi (6.0 mL, 2.6 M in hexanes, 15.0 mmol), and crude aldehyde 14 (about 4.6 mmol) [prepared from alcohol 13 by Dess-Martin oxidation], dissolved in THF (5 mL) were converted to alcohol 15 (0.91 g, 63%), slightly yellow oil. TLC (petroleum ether/EtOAc, 1:1): R_f = 0.53; ¹H NMR (250 MHz, CDCl₃): δ = 1.01 (s, 3 H, CH₃), 1.07 (s, 3 H, CH₃), 2.09 (d, J = 4.6 Hz, 1 H, OH), 3.37 (s, 3 H, OCH₃), 3.52-3.70 (m, 4 H, OCH₂CH₂O), 4.09 (d, J = 6.4 Hz, 2 H, H-7), 4.39 (d, J = 4.6 Hz, 1 H, H-1), 4.71 (s, 2 H, OCH₂O), 5.64-5.80 (m, 2 H, H-3, H-6), 6.08 (dd, J = 10.2, 15.3 Hz, 1 H, H-4), 6.19 (d, J = 3.4 Hz, 1 H, furan H-3), 6.23 (dd, J = 10.2, 15.1 Hz, 1 H, H-5), 6.30 (dd, J = 1.5, 3.4 Hz, 1 H, furan H-4), 7.33 (d, J = 1.5 Hz, 1 H, furan H-5); ¹³C NMR (63 MHz, CDCl₃): δ = 22.77 (CH₃), 24.09 (CH₃), 41.68 (C-2), 58.92 (OCH₃), 67.58 (OCH₂CH₂OMe), 71.77 (CH₂OMe), 94.61 (OCH₂O), 109.39 (furan C-3), 110.00 (furan C-4), 127.81 (C-4), 128.47 (C-6), 133.24 (C-3), 140.51 (C-5), 141.45 (furan C-5), 154.79 (furan C-2); MS (FD): m/z (%) = 310.2(6) [M]⁺, 213.2(100) [M - C₅H₅O₂]⁺.
(2 R ,3a R ,4 S ,5 S ,7a R )-2-hydroxy-5-{[(2-methoxy-ethoxy)methoxy]methyl}-1,1-dimethyl-3-oxo-2,3,3a,4,5,7a-hexahydro-1 H -indene-4-carbaldehyde (18). As described for compound 6, furfuryl alcohol 15 (870 mg, 2.8 mol) was rearranged using vanadylacetyl acetonate (40 mg, 0.15 mmol) in CH₂Cl₂ (20 mL) and tert-butylhydroperoxide (0.8 mL, 3.3 mmol), dissolved in CH₂Cl₂ (5 mL). The crude hydroxypyranone 16 was thermolyzed in toluene (30 mL), containing hydroquinone (about 5 mg) to provide decalin 18 (475 mg, 52%) as colorless oil. TLC (CH₂Cl₂/EtOAc, 2:1): R_f = 0.33; ¹H NMR (250 MHz, CDCl₃): δ = 0.58 (s, 3 H, CH₃), 1.28 (s, 3 H, CH₃), 2.28 (ddd, J = 2.5, 9.1, 11.8 Hz, 1 H, H-4), 2.50-2.56 (m, 1 H, H-5), 2.69 (ddd, J = 3.0, 10.5 Hz, 1 H, H-7a), 2.81 (s, 1 H, OH), 3.10 (ddd, J = 1.6, 10.5, 11.8 Hz, 1 H, H-3a), 3.35 (s, 3 H, OCH₃), 3.42 (dd, J = 7.8, 9.6 Hz, 1 H, CH₂OMEM), 3.50-3.53 (m, 2 H, OCH₂CH₂O), 3.61 (dd, J = 5.3, 9.6 Hz, 1 H, CH₂OMEM), 3.62-3.64 (m, 2 H, OCH₂CH₂O), 4.10 (d, J = 1.6 Hz, 1 H, H-2), 4.64 (s, 2 H, OCH₂O),5.70 (ddd, J = 2.1, 10.1 Hz, 1 H, H-7), 5.80 (ddd, J = 3.0, 10.1 Hz, 1 H, H-6), 10.09 (d, J = 2.5 Hz, 1 H, CHO); ¹³C NMR (63 MHz, CDCl₃): δ = 17.18 (CH₃), 25.64 (CH₃), 37.59 (C-5), 40.82 (C-7a), 42.14 (C-3a), 48.21 (C-4), 58.94 (OCH₃), 67.01 (OCH₂CH₂OMe), 70.00 (CH₂OMEM), 71.64 (OCH₂CH₂OMe), 83.89 (C-2), 95.36 (OCH₂O),124.27 (C-6), 128.56 (C-7), 203.87 (CHO), 216.19 (C-3); IR(film): 2930, 2876, 1747, 1721, 1115, 1042 cm^-1; MS (FD): m/z (%) = 326.3(100) [M]⁺.