Synlett 2007(15): 2430-2432  
DOI: 10.1055/s-2007-985579
LETTER
© Georg Thieme Verlag Stuttgart · New York

Application of the Nitroaldol (Henry) Reaction for a Two-Step Sequence in the Synthesis of Polyfunctionalized Dihydropyran Derivatives

Roberto Ballini*, Serena Gabrielli, Alessandro Palmieri
Dipartimento di Scienze Chimiche, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy
Fax: +39(0737)402297; e-Mail: Roberto.ballini@unicam.it;
Further Information

Publication History

Received 17 April 2007
Publication Date:
13 August 2007 (online)

Abstract

Nitroaldol (Henry) reaction of a variety of nitroalkanes, under neat t-BuOK catalysis, allows a one-pot synthesis of polyfunctionalized tetrahydropyranols which, with CeCl3·7H2O/NaI system, dehydrate to dihydropyran derivatives. Thus, the dihydro­pyrans can be obtained in only two steps from nitroalkanes.

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General Procedure for the Preparation of Dihydropyrans 5: To a stirred solution of aldehyde 1 (0.186 g, 1.0 mmol) and nitroalkane 2 (1.0 mmol), cooled at 0 °C, t-BuOK (33.6 mg, 0.3 mmol) was added. After 5 min the mixture was stirred at r.t. for 6-9 h (TLC), then treated with 0.5 N HCl (5 mL) and extracted with Et2O (3 × 10 mL). The combined layers were dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. To the obtained crude compound 4, dissolved in MeCN (10 mL), cerium(III) chloride heptahydrate (1.5 mmol) and NaI (1.5 mmol) were added and the obtained solution was refluxed for 6-8 h (TLC). The reaction mixture was then treated with 0.5 N HCl (5 mL) and the organic phase was extracted with Et2O (3 × 10 mL). The organic layer was dried (Na2SO4), filtered, evaporated and purified by flash chromatography (hexane-EtOAc, 9:1), yielding the pure dihydropyranols 5.

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Selected Analytical Data for Compounds 5′a,h,k and 5′′a,h,k: Compound 5a′: waxy solid. IR: 1702, 1638, 1562 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.97 (t, J = 7.3 Hz, 3 H), 1.24 (t, J = 7.2 Hz, 3 H), 1.50-1.61 (m, 1 H), 1.74-1.85 (m, 1 H), 1.88-2.01 (m, 2 H), 2.14 (s, 3 H), 2.20-2.31 (m, 1 H), 2.35-2.44 (m, 1 H), 4.12 (q, J = 7.3 Hz, 2 H), 4.25 (dt, J = 2.6, 9.0 Hz, 1 H), 4.42-4.50 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ = 10.2, 14.6, 20.1, 20.7, 23.0, 23.1, 60.1, 76.0, 92.3, 101.9, 163.3, 168.1. EIMS (70 eV): m/z = 257, 240, 212, 149, 139, 121, 97, 55, 43 (100), 29. Anal. Calcd for C12H19NO5 (257.28): C, 56.02; H, 7.44; N, 5.44. Found: C, 56.56; H, 7.68; N, 5.12.
Compound 5a′′: yellow oil. IR: 1706, 1633, 1557 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.99 (t, J = 7.3 Hz, 3 H), 1.25 (t, J = 7.2 Hz, 3 H), 1.55-1.67 (m, 1 H), 1.87-1.95 (m, 1 H), 1.96-2.14 (m, 2 H), 2.17-2.30 (m, 1 H), 2.20 (s, 3 H), 2.40-2.51 (m, 1 H), 4.09-4.17 (m, 3 H), 4.46-4.53 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ = 10.5, 14.6, 20.1, 20.9, 23.4, 23.5, 60.1, 75.6, 91.5, 102.4, 163.4, 168.2. EIMS (70 eV): m/z = 257, 240, 212, 149, 139, 121, 97, 55, 43 (100), 29. Anal. Calcd for C12H19NO5 (257.28): C, 56.02; H, 7.44; N, 5.44. Found: C, 56.41; H, 7.71; N, 5.24.
Compound 5h′: waxy solid. IR: 1740, 1703, 1635, 1551 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.25 (t, J = 7.3 Hz, 3 H), 1.28-1.45 (m, 2 H), 1.50-1.77 (m, 4 H), 1.91-2.03 (m, 2 H), 2.15 (s, 3 H), 2.20-2.35 (m, 3 H), 2.37-2.46 (m, 1 H), 3.64 (s, 3 H), 4.14 (q, J = 7.3 Hz, 2 H), 4.21-4.27 (m, 1 H), 4.51-4.58 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ = 14.6, 20.1, 20.7, 23.1, 24.3, 25.2, 29.3, 33.7, 51.9, 60.1, 76.0, 90.7, 102.0, 163.3, 168.1, 173.7. EIMS: m/z = 343, 312, 298, 251, 167, 139, 97, 55, 43 (100), 29. Anal. Calcd for C16H25NO7 (343.37): C, 55.97; H, 7.34; N, 4.08. Found: C, 56.25; H, 7.55; N, 3.91.
Compound 5h′′: yellow oil. IR: 1737, 1706, 1633, 1557 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.25 (t, J = 7.3 Hz, 3 H), 1.30-1.43 (m, 2 H), 1.53-1.75 (m, 4 H), 1.85-1.99 (m, 2 H), 2.19 (s, 3 H), 2.20-2.35 (m, 3 H), 2.40-2.52 (m, 1 H), 3.64 (s, 3 H), 4.08-4.18 (m, 3 H), 4.52-4.58 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ = 14.6, 20.1, 20.9, 23.4, 24.4, 25.5, 29.6, 33.7, 51.8, 60.1, 75.7, 89.9, 102.4, 163.3, 168.1, 173.8. EIMS: m/z = 343, 312, 298, 251, 167, 139, 97, 55, 43 (100), 29. Anal. Calcd for C16H25NO7 (343.37): C, 55.97; H, 7.34; N, 4.08. Found: C, 56.27; H, 7.51; N, 3.87.
Compound 5k′: yellow oil. IR: 1719, 1641, 1556 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.25 (t, J = 7.3 Hz, 3 H), 1.59-1.69 (m, 1 H), 1.98-2.11 (m, 1 H), 2.12-2.35 (m, 9 H), 2.41-2.62 (m, 3 H), 4.15 (q, J = 7.3 Hz, 2 H), 4.27 (dt, J = 2.6, 9.8 Hz, 1 H), 4.56-4.64 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ = 14.6, 20.1, 20.6, 23.1, 23.4, 30.3, 38.7, 60.2, 76.0, 89.9, 102.1, 163.2, 168.1, 206.2. EIMS: m/z = 299, 254, 163, 97, 55, 43 (100), 29. Anal. Calcd for C14H21NO6 (299.32): C, 56.18; H, 7.07; N, 4.68. Found: C, 55.88; H, 6.89; N, 4.79.
Compound 5k′′: yellow oil. IR: 1715, 1631, 1557 cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.24 (t, J = 7.3 Hz, 3 H), 1.56-1.67 (m, 1 H), 1.88-1.95 (m, 1 H), 2.10-2.33 (m, 3 H), 2.13 (s, 3 H), 2.17 (s, 3 H), 2.41-2.63 (m, 3 H), 4.12 (q, J = 7.3 Hz, 2 H), 4.16-4.21 (m, 1 H), 4.56-4.62 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ = 14.6, 20.1, 21.0, 23.2, 23.4, 30.2, 39.1, 60.1, 75.9, 88.9, 102.4, 163.4, 168.1, 206.6. EIMS: m/z = 299, 254, 163, 97, 55, 43 (100), 29. Anal. Calcd for C14H21NO6 (299.32): C, 56.18; H, 7.07; N, 4.68. Found: C, 56.45; H, 7.32; N, 4.28.