Download PDF
Synlett 2005(1): 91-94  
DOI: 10.1055/s-2004-836056
LETTER
© Georg Thieme Verlag Stuttgart · New York

Zr(Ot-Bu)4-Catalyzed Tishchenko Reduction of β-Hydroxy Ketones

Christoph Schneider*, Katharina Klapa, Markus Hansch
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Fax: +49(341)9736599; e-Mail: schneider@chemie.uni-leipzig.de;
Further Information

Publication History

Received 13 October 2004
Publication Date:
02 December 2004 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

Zr(OtBu)4 was found to catalyze the Tishchenko reduction of β-hydroxy ketones giving rise to differentiated 1,3-anti-diol monoesters in high yields and excellent stereoselectivity.

Key words

catalysis - diastereoselectivity - 1,3-diols - Tishchenko reduction - zirconium

18

Representative Experimental Procedure. Synthesis of Product 7b: To a stirred solution of 3-hydroxy-4-methyl-1-phenyl-1-pentanone (1, 192 mg, 1.00 mmol) and isobutyraldehyde (2, 137 µL, 1.50 mmol) in dry toluene (5 mL) was added Zr(Ot-Bu)4 (20 µL, 0.050 mmol) at -30 °C. The resulting solution was stirred for 30 min at -30 °C before addition of 0.5 M aq HCl solution (4 mL). The layers were separated and the aqueous layer was extracted with Et2O (3 × 15 mL). The combined organic layers were dried over MgSO4, filtered and the solvent was removed under reduced pressure. Flash chromatography (silica gel, Et2O-pentane 1:4) of the crude product yielded 7b as a colorless oil (238 mg, 90%).

19

Representative Spectroscopic Data: Compound 7b: 1H NMR (200 MHz, CDCl3): δ = 0.93 [d, J = 7.0 Hz, 3 H, CH(CH 3)2], 0.94 [d, J = 7.0 Hz, 3 H, CH(CH 3)2], 1.23 [d, J = 7.0 Hz, 6 H, CH(CH 3)2], 1.98-1.75 [m, 3 H, CH2, CH(CH3)2], 2.65 [sept, J = 7.0 Hz, 1 H, CH(CH3)2], 3.30 (br s, 1 H, OH), 4.54 (dd, J = 7.5, 5.5 Hz, 1 H, CHOH), 5.05 (dt, J = 8.0, 5.5 Hz, 1 H, CHOCOR), 7.40-7.25 (m, 5 H, ArH). 13C NMR (50 MHz, CDCl3): δ = 17.50, 18.72, 19.18, 19.23, 32.16, 34.39, 42.14, 69.82, 75.36, 125.5, 127.3, 128.4, 144.0, 178.5. IR (film): 3489, 3063, 3029, 2968, 2877, 1731, 1470, 1389, 1269, 1201, 1162, 1052, 758, 701 cm-1. MS (200 eV, DCI/NH3): m/z (%) = 810 (1) [3 M + NH4 +], 546 (20) [2 M + NH4 +], 282 (50) [M + NH4 +], 247 (100) [M+ - OH]. Anal. Calcd (%) for C16H24O3 (264.36): C, 72.69; H, 9.15. Found: C, 72.68; H, 8.92.
Compound 7f: 1H NMR (200 MHz, CDCl3): δ = 0.89 [s, 9 H, C(CH3)3], 0.93 [d, J = 7.0 Hz, 6 H, CH(CH 3)2], 1.20 [d, J = 7.0 Hz, 6 H, CH(CH 3)2], 1.47 (ddd, J = 14.0, 10.5, 2.0 Hz, 1 H, CHH), 1.65 (ddd, J = 14.0, 10.5, 2.0 Hz, 1 H, CHH), 1.95-1.75 [m, 1 H, CH(CH3)2], 2.50 (br s, 1 H, OH), 2.61 [sept, J = 7.0 Hz, 1 H, CH(CH3)2], 3.00 (dd, J = 10.5, 2.0 Hz, 1 H, CHOH), 4.95 (ddd, J = 10.5, 5.0, 2.0 Hz, 1 H, CHOCOR). 13C NMR (50 MHz, CDCl3): δ = 17.63, 18.97, 19.20, 19.26, 25.94, 32.37, 33.96, 34.41, 34.42, 74.73, 75.81, 178.40. IR (film): 3518, 2967, 2876, 1714, 1389, 1267, 1204, 1163, 1070, 1011 cm-1. MS (200 eV, DCI/NH3): m/z (%) = 279 (2) [M + NH3 + NH4 +], 262 (100) [M + NH4 +], 245 (5) [M + H+]. Anal. Calcd (%) for C14H28O3 (244.37): C, 68.81; H, 11.55. Found: C, 69.08; H, 11.29.