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Synlett 2014; 25(6): 817-820
DOI: 10.1055/s-0033-1340739
letter
© Georg Thieme Verlag Stuttgart · New York

Prins Cyclization Using Magnesium Halides: Mild Access to 4-Halogenated Polysubstituted Tetrahydropyrans with a Special Feature

Mario Walter
Chemisches Institut, Otto-von-Guericke-Universität, Universitätsplatz 2, 39104 Magdeburg, Germany   Fax: +49(391)6712223   eMail: dieter.schinzer@ovgu.de
,
Dieter Schinzer*
Chemisches Institut, Otto-von-Guericke-Universität, Universitätsplatz 2, 39104 Magdeburg, Germany   Fax: +49(391)6712223   eMail: dieter.schinzer@ovgu.de
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Publikationsverlauf

Received: 20. Dezember 2013

Accepted after revision: 13. Januar 2014

Publikationsdatum:
13. Februar 2014 (online)

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Abstract

Different 4-halo-substituted polyfunctionalized tetra­hydropyrans were easily synthesized by segment-coupling Prins cyclization utilizing magnesium halides. The moderate Lewis acidity allows transformation of substrates bearing acid-labile functional groups. A solvent dependency of the stereochemistry at the C4 carbon was observed.

Key words

Prins cyclization - magnesium halides - halogenated tetrahydropyrans - solvent-dependent stereochemistry - polysubstituted tetrahydropyrans
 

  • References and Notes

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  • 16 General Procedure for Prins Cyclization of 8 Magnesium halide (2 equiv) was added to a solution of acetoxy ether 8 in the respective solvent (mixture; 5–10 mL/mmol of 8) at given temperatures. Reaction mixture was stirred for 1–2 h and quenched with sat. NaHCO3 solution and extracted three times with CH2Cl2. The combined organic extracts were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (pentane–Et2O, 7:1). Spectroscopical Data for (2R,3S,4R,6R)-2-(2-Benzyloxyethyl)-4-bromo-6-[(4R,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl]-3-methyltetrahydropyran (7a) Yield 82%; colorless oil; [a]D +43 (c 2.00, CHCl3). 1H NMR (600 MHz, CDCl3): δ = 7.27–7.37 (5 H, m, C6H5), 5.83 (1 H, ddd, J = 16.8, 10.0, 6.5 Hz, CH=CH2), 5.34 (1 H, dd, J = 17.1, 1.5 Hz, CH=CH 2), 5.14 (1 H, d, J = 10.5 Hz, CH=CH 2), 4.64 (1 H, dd, J = 6.3, 6.3 Hz, CHCH=CH2), 4.44–4.51 (2 H, m, CH2Ph), 4.42 (1 H, dt, J = 12.8, 4.3 Hz, H-4), 3.97 (1 H, dd, J = 8.4, 6.3 Hz, 6-CH), 3.39–3.52 (1 H, m, H-2), 3.48–3.52 (2 H, m, CH2CH 2OBn), 3.36 (1 H, td, J = 9.8, 2.4 Hz, H-6), 2.20 (1 H, dt, J = 10.2, 2.8 Hz, H-5), 1.92–1.99 (2 H, m, H-5 and H-3), 1.78–1.85 (1 H, m, CH 2CH2OBn), 1.60–1.66 (1 H, m, CH 2CH2OBn), 1.45 [3 H, s, C(CH3)2], 1.36 [3 H, s, C(CH3)2], 1.07 (3 H, d, J = 6.9 Hz, 3-CH3). 13C NMR (100 MHz, CDCl3): δ = 138.2 (Car,q), 133.6 (CH=CH2), 128.4 (Car), 127.6 (Car), 117.4 (CH=CH2), 108.7 [C(CH3)2], 79.2 (6-CH), 78.6 (CHCH=CH2), 76.6 (C-2), 76.3 (C6), 73.0 (CH2Ph), 66.9 (CH2 CH2OBn), 54.0 (C-4), 39.7 (C-3), 34.6 (C-5), 33.9 (CH2CH2OBn), 27.7 [C(CH3)2], 25.3 [C(CH3)2], 7.6 (3-CH3). MS: m/z (%) = 424 (70), 422 (70), 301 (50), 231 (75), 141 (55), 137 (70), 127 (100). HRMS: m/z calcd for C22H31BrO4: 438.1403 [M]+; found: 438.1404.