A Novel Strategy for the Convergent Synthesis of 1,3,5,…-Polyols: Enone Formation, Asymmetric Dihydroxylation, Reductive Cleavage, Hydride Addition

Karsten Körber; Philippe Risch; Reinhard Brückner

doi:10.1055/s-2005-921915

LETTER

A Novel Strategy for the Convergent Synthesis of 1,3,5,…-Polyols: Enone Formation, Asymmetric Dihydroxylation, Reductive Cleavage, Hydride Addition

Karsten Körber, Philippe Risch, Reinhard Brückner*
Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany
Fax: +49(761)2036100; e-Mail: reinhard.brueckner@organik.chemie.uni-freiburg.de;

Abstract

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Abstract

Asymmetric dihydroxylation of α,β-unsaturated ketones provided α,β-dihydroxyketones with up to 100% ee. The C^α-O bond of these intermediates or their bis-TMS ethers, acetonides, phenylborates or orthoformiates was cleaved with SmI₂, affording β-hydroxyketones. The latter can be reduced to furnish syn- or anti-configured 1,3-diols of any desired configuration.

Key words

defunctionalization - 1,3-diol - Horner-Wadsworth-Emmons olefination - β-hydroxy ketones - samarium iodide - α,β-unsaturated ketones

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References

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(3 S ,4 R )-3,4-Dihydroxy-2-octanone (α S ,β R -10a).
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<A NAME="RG29405ST-18B">18b</A> Similarly an O^α-SiMe₂ t-Bu bond was cleaved off a ketone by: Abad A. Agulló C. Arnó M. Cuñat AC. García MT. Zaragozá RJ. J. Org. Chem. 1996, 61: 5916

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<A NAME="RG29405ST-23">23</A> Molander GH. Hahn G. J. Org. Chem. 1986, 51: 2596

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(4 R )-4-Hydroxy-2-octanone ( 11a).
At -78 °C a solution of SmI₂ (0.1 M in THF, 42 mL, 4.2 mmol, 2.1 equiv) was added dropwise to a stirred solution of acetonide αS,βR-12a (0.40 g, 2.0 mmol) in THF (12 mL) and MeOH (6 mL). After 15 min the reaction mixture was gradually warmed to r.t. (within 30 min) and aq HCl (1 M, 4.2 mL) was added. After evaporating volatile material in vacuo the residue was diluted with H₂O (10 mL) and extracted with t-BuOMe (3 × 15 mL). The combined organic extracts were washed with sat. aq NaHCO₃ (10 mL) and brine (8 mL) and dried over MgSO₄. Removal of the solvent in vacuo and purification of the residue by flash chromatography on silica gel [11] (column filling 1.5 cm × 15 cm, cyclohexane-EtOAc 4:1, 4 mL fractions) afforded the title compound (fractions 20-39, 0.186 g, 65%) as a colorless oil. ¹H NMR (400 MHz, MHz, TMS internal standard in CDCl₃): δ = 0.91 (t, J _8,7 = 7.1 Hz, 8-H₃), 1.29-1.54 (m, 5-H₂, 6-H₂, 7-H₂), 2.18 (s, 1-H₃), AB signal (δ_A = 2.53, δ_B = 2.62, J _AB = 17.7 Hz, A part in addition split by J _A,4 = 9.0 Hz, B part in addition split by J _B,4 = 2.9 Hz, 3-H₂), 2.94 (br s, 4-OH), 4.03 (m_c, 4-H). [α]_D ²⁰ -31.50 (c 0.20, CHCl₃). IR (CDCl₃): δ = 3565, 2960, 2935, 2875, 2860, 1705, 1470, 1460, 1415, 1385, 1365, 1315, 1275, 1165, 1060 cm^-1. Anal. Calcd for C₈H₁₆O₂ (144.2): C, 66.63; H, 11.18. Found: C, 66.74; H, 10.97.

<A NAME="RG29405ST-28B">28b</A> Enantiomer S-11a was prepared by an organocatalytic aldol addition (86% ee, 12% yield). See: Tang Z. Jiang F. Yu L.-T. Cui X. Gong L.-Z. Mi A.-Q. Jiang Y.-Z. Wu Y.-D. J. Am. Chem. Soc. 2003, 125: 5262

Borinylated β-hydroxyketone and NaBH₄:

<A NAME="RG29405ST-29A">29a</A> Narasaka K. Pai F.-C. Chem. Lett. 1980, 1415

<A NAME="RG29405ST-29B">29b</A> Narasaka K. Pai F.-C. Tetrahedron 1984, 40: 2233

<A NAME="RG29405ST-29C">29c</A> Chen K.-M. Hardtmann GE. Prasad K. Repic O. Shapiro MJ. Tetrahedron Lett. 1987, 28: 155

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<A NAME="RG29405ST-30">30</A> BCl₃-complexed β-hydroxyketone and tetraalkylammonium boronate: Sarko CS. Collibee SE. Knorr AR. DiMare M. J. Org. Chem. 1996, 61: 868

<A NAME="RG29405ST-31">31</A> Reduction with DIBAL-H: Kiyooka S. Kuroda H. Shimasaki Y. Tetrahedron Lett. 1986, 27: 3009

<A NAME="RG29405ST-32">32</A> Reduction with catecholborane: Evans DA. Hoveyda AH. J. Org. Chem. 1990, 55: 5190

<A NAME="RG29405ST-33A">33a</A> Reduction with Zn(BH₄)₂: Kashihara H. Suemune H. Fujimoto K. Sakai K. Chem. Pharm. Bull. 1989, 37: 2610 ; in Et₂O

<A NAME="RG29405ST-33B">33b</A> Dakin LA. Panek JS. Org. Lett. 2003, 5: 3995 ; in CH₂Cl₂

Reduction with tetraalkylammonium triacetoxyboro-hydride:

<A NAME="RG29405ST-34A">34a</A> Evans DA. Chapman KT. Tetrahedron Lett. 1986, 27: 5939

<A NAME="RG29405ST-34B">34b</A> Evans DA. Chapman KT. Carreira EM. J. Am. Chem. Soc. 1988, 110: 3560

<A NAME="RG29405ST-34C">34c</A> See also with sodium triacetoxyborohydride: Roeyeke Y. Keller M. Kluge H. Grabley S. Hammann P. Tetrahedron 1991, 47: 3335

Intramolecular hydrosilylation:

<A NAME="RG29405ST-35A">35a</A> Anwar S. Davis AP. J. Chem. Soc., Chem. Commun. 1986, 831

<A NAME="RG29405ST-35B">35b</A> Anwar S. Davis AP. Tetrahedron 1988, 44: 3761

<A NAME="RG29405ST-36A">36a</A> Reduction with SmI₂ and an aldehyde: Evans DA. Hoveyda AH. J. Am. Chem. Soc. 1990, 112: 6447

Related Tishchenko reductions:

<A NAME="RG29405ST-36B">36b</A> Schneider C. Klapa K. Hansch M. Synlett 2005, 91 and literature cited therein

<A NAME="RG29405ST-37">37</A> LiClO₄-complexed β-hydroxyketone and amine-complexed BH₃: Narayana C. Reddy MR. Hair M. Kabalka GW. Tetrahedron Lett. 1997, 38: 7705

<A NAME="RG29405ST-38A">38a</A> Reduction with SmI₂: Keck GE. Wager CA. Sell T. Wager TT. J. Org. Chem. 1999, 64: 2172

<A NAME="RG29405ST-38B">38b</A> The diastereoselectivity of this reduction is sensitive to solvent variation: Chopade PR. Davis TA. Prasad E. Flowers RA. Org. Lett. 2004, 6: 2685

<A NAME="RG29405ST-39">39</A> LiI-complexed β-hydroxyketone and LiAlH(Ot-Bu)₃: Ball M. Baron A. Bradshaw B. Omori H. MacCormick S. Thomas EJ. Tetrahedron Lett. 2004, 45: 8737

Methyl (6 R )-7-[(4 R )-2,2-Dimethyl-1,3-dioxolan-4-yl]-6-hydroxy-4-oxoheptanoate ( 24).
A suspension of 1,2-diiodoethane (2.062 g, 7.316 mmol, 3.0 equiv) and Sm powder 40 mesh (1.155 g, 7.316 mmol, 3.15 equiv) in THF (70 mL) was stirred at r.t. for 2 h. A deep-blue solution of SmI₂ was obtained. At -78 °C acetonide 25 (805 mg, 2.44 mmol) in THF-MeOH 2:1 (30 mL) was added within 10 min. After another 10 min, the mixture was warmed to r.t. and the reaction quenched 20 min later by the addition of aq HCl (1 M, 7.4 mL). The aqueous phase was separated and extracted with t-BuOMe (3 × 25 mL). The combined organic phases were washed successively with sat. aq NaHCO₃ (15 mL) and brine (12 mL) and dried over MgSO₄. Removal of the solvent in vacuo and purification of the residue by flash chromatography on silica gel [11] (column filling 3 cm × 20 cm, eluent = cyclohexane-EtOAc, 40:60) provided the title compound (fractions 8-24, 601 mg, 90%). ¹H NMR (500 MHz, CDCl₃): δ = 1.36 and 1.41 [2 × s, 2′-(CH₃)₂], AB signal (δ_A = 1.69, δ_B = 1.73, J _AB = 13.1 Hz, in addition split by J _7-H ₍ _A),6 = 7.3 Hz,* J _7-H ₍ _A),4 _′ = 4.1 Hz,*
J _7-H ₍ _B),4 _′ = 8.3 Hz,** J _7-H ₍ _B),6 = 4.9 Hz,** 7-H₂), presumably extreme AB signal where the 8 off-center signals are too small to be identified (so that J _AB cannot be extracted) so that the best description is: 2.61 (dd, J _3-H ₍ _1),2-H ₍ ₁₎ = 6.6 Hz, J _3-H ₍ _1),2-H ₍ ₂₎ = 3.8 Hz), 2.62 (dd, J _3-H ₍ _2),2-H ₍ ₂₎ = 6.6 Hz,***
J _3-H ₍ _2),2-H ₍ ₁₎ = 2.7 Hz,*** 3-H₂), 2.68 and 2.76 (2 × m_c, 2-H₂, 5-H₂), 3.26 (d, J _OH,6 = 3.5 Hz, 6-OH), 3.57 (dd, J _gem = J ₅ _′ _-H ₍ _1),4 _′ = 7.8 Hz, 5′-H¹), 3.68 (s, 1-OCH₃), 4.09 (dd, J _gem = 7.9 Hz, J ₅ _′ _-H ₍ _2), ₄ _′ = 6.1 Hz, 5′-H²), 4.25-4.33 (m, 6-H, 4′-H); *, **, *** coupling constants exchangeable. ¹³C NMR [75 MHz, CDCl₃; APT spectrum, peak orientation ‘up’ (‘+’) for CH₃ and CH and ‘down’ (‘-’) for CH₂ and C_quat]: δ = ‘+’ 25.67 and ‘+’ 26.91 [2′-(CH₃)₂], ‘-’ 27.55 (C-2), ‘-’ 37.80 (C-3), ‘-’ 39.94 (C-7), ‘-’ 49.66 (C-5), ‘+’ 51.88 (1-OCH₃), ‘+’ 65.46 (C-6), ‘-’ 69.64 (C-5’), ‘+’ 73.37 (C-4’), ‘-’ 108.75 (C-2’), ‘-’ 173.21 (C-1), ‘-’ 209.34 (C-4). [α]_D ²⁰
-22.6 (c 1.92, CHCl₃). IR (film): 3490, 3015, 2985, 2945, 1735, 1715, 1435, 1415, 1370, 1215, 1165, 1060, 990, 870, 855 cm^-1. Anal. Calcd for C₁₃H₂₂O₆ (274.3): C, 56.92; H, 8.08. Found: C, 57.12; H, 7.99.