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Synlett 2003(6): 0837-0840
DOI: 10.1055/s-2003-38741
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

First Catalytic, Enantioselective Aldol-Tishchenko Reactions with Ketone Aldols as Enol Equivalents

Christoph Schneider*, Markus Hansch
Institut für Organische Chemie der Georg-August-Universität Göttingen, Tammannstr. 2, 37077 Göttingen, Germany
Fax: +49(551)399660; e-Mail: cschnei1@gwdg.de;
Further Information

Publication History

Received 19 February 2003
Publication Date:
17 April 2003 (online)

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Abstract

Chiral zirconiumTADDOLates were found to catalyze the aldol-Tishchenko reaction of diacetone alcohol (1a) and two other ketone aldol adducts 1b and 1c with a range of aldehydes giving rise to differentiated 1,3-anti-diol monoesters in good yields, complete diastereocontrol and moderate enantioselectivities.

Key words

aldol reaction - asymmetric catalysis - ketone aldols - Tishchenko reduction - zirconium

    References

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  • 18e

    The absolute configuration of all other products was assigned in analogy to these experiments
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17

All new products were fully characterized by 1H and 13C NMR, IR, MS and elemental analysis. Representative spectroscopic data: 3a: [α]D 20 = +8.9° (c = 1.0, CHCl3, 47% ee); IR (film): 3452, 2969, 2936, 2878, 1731, 1272, 1202, 1163, 1072 cm-1; 1H (200 MHz, CDCl3): δ = 0.94 (d, J = 7.0 Hz, 6 H, i-Pr), 1.19 (d, J = 7.0 Hz, 3 H, CH3) 1.22 (d, J = 7.0 Hz, 6 H, i-Pr), 1.56 (m, 2 H, CH2), 1.81 [m, 1 H, CH(CH3)2], 2.61 [sept, J = 7.0 Hz, 1 H, CH(CH3)2], 3.02 (br s, 1 H, OH), 3.58 (m, 1 H, CHOH), 4.88 (m, 1 H, CHOCOR); 13C (50 MHz, CDCl3): δ = 17.61, 18.87, 19.14, 19.23, 22.91, 32.16, 34.39, 41.61, 63.25, 75.49, 178.6; MS (200 eV, DCI/NH3): m/z = 422(1) [2M + NH4 +], 237(3) [M + NH3 + NH4 +], 220(100) [M + NH4 +], 202(8) [M + H+]; Calculated for C11H22O3 (202.29): C 65.31, H 10.96; Found C 65.22, H 11.02; 10b: [α]D 20 = +11.5 (c = 0.85, CHCl3, 57% ee); IR (film): 3518, 2967, 2876, 1714, 1389, 1267, 1204, 1163, 1070, 1011 cm-1; 1H (200 MHz, CDCl3): δ = 0.89 (s, 9 H, t-Bu), 0.93 (d, J = 7.0 Hz, 6 H, i-Pr), 1.20 (d, J = 7.0 Hz, 6 H, i-Pr), 1.28-1.72 (m, 2 H, CH2), 1.75-1.95 [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 Hz, 5.0 Hz, 2.0 Hz, 1 H, CHOCOR); 13C (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, 178.4; MS (200 eV, DCI/NH3): m/z = 279 (1) [M + NH3 + NH4 +], 262 (100) [M + NH4 +]. Calculated for C14H28O3 (244.37): C 68.81, H 11.55; Found: C 69.08, 11.29.

19

The following Zr-BINOLate complexes were tested in the reaction of 1a and 2a under otherwise identical reaction conditions: Zr(t-BuO)4/(R)-BINOL: 31% yield (28% ee); Zr(t-BuO)4/(R)-6,6′-Br2-BINOL: 35% yield (25% ee); Zr(t-BuO)4/(R)-3,3′-Br2-BINOL: 62% yield (0% ee); Zr(t-BuO)4/(R)-3,3′-Ph2-BINOL: 89% yield (28% ee).

20

Prepared by the l-proline-catalyzed aldol addition of acetone and isobutyraldehyde according to ref. [4]