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Synlett 2005(19): 2905-2910  
DOI: 10.1055/s-2005-921915
LETTER
© Georg Thieme Verlag Stuttgart · New York

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;
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Publication History

Received 27 September 2005
Publication Date:
04 November 2005 (online)

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Abstract

Asymmetric dihydroxylation of α,β-unsaturated ketones provided α,β-dihydroxyketones with up to 100% ee. The Cα-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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Compounds αS,βR-10a-g, αR,βS-10a-g, 11a-g, αR,βS-12c, 13, 15, 17, 18, syn-21, and anti-21 provided correct 1H NMR spectra and combustion analyses. Compounds αS,βR-12a-g except c were too volatile for combustion analysis and intermediates 14, 16, and 19 deemed not worth it; these compounds were characterized by 1H NMR and low-resolution mass spectra only.

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(3 S ,4 R )-3,4-Dihydroxy-2-octanone (α S ,β R -10a).
At 0 °C, trans-3-octen-2-one (1.20 g, 1.38 mL, 9.51 mmol) was added to a stirred mixture of K2OsO2(OH)4 (35.0 mg, 0.095 mmol, 1.0 mol%), (DHQD)2PHAL (370.0 mg, 0.475 mmol, 5.0 mol%), NaHCO3 (2.40 g, 28.5 mmol, 3.0 equiv), K2CO3 (3.95 g, 28.5 mmol, 3.0 equiv), MeSO2NH2 (903 mg, 9.51 mmol, 1 equiv), and K3Fe(CN)6 (9.39 g, 28.5 mmol, 3.0 equiv) in t-BuOH (25 mL) and H2O (25 mL). After stirring for 60 h sat. aq Na2SO3 (120 mL) was added. The mixture was warmed to r.t. and extracted with EtOAc (3 × 70 mL). The combined organic extracts were washed with brine (60 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 5 cm × 20 cm, cyclohexane-EtOAc 1:2, 60 mL fractions) provided the title compound (fractions 5-8, 1.39 g, 89%) as a colorless oil. The ee was ³99% according to chiral GC {CP-Chirasil-Dex CB 25 m × 0.25 mm catalog number CP7502; from 60 °C/10 min at 5 °C/min to 170 °C/20 min; 80 kPa, t R (major enantiomer) = 26.46 min; no compound eluted around t R = 25.71 min [which was the independently measured value of t R (minor enantiomer)]}. 1H NMR (500 MHz, TMS internal standard in CDCl3): δ = 0.93 (t, J 8,7 = 7.1 Hz, 8-H3), 1.34-1.42 (m, 7-H2, 6-H1), 1.44-1.50 (m, 6-H2), 1.66 (mc, presumably interpretable as ddd, J 5,4 = J 5,6-H ( 1) = J 5,6-H ( 2) = 6.9 Hz, 5-H2), superimposed partly by 1.73 (br s, 4-OH), 2.28 (s, 1-H3), 3.70 (br s, 3-OH), 3.95 (td, J 4,5 = 6.9 Hz, J 4,3 = 1.4 Hz, 4-H), 4.08 (d, J 3,4 = 1.5 Hz, 3-H). [α]D 20 +94.6 (c 0.45, CHCl3). IR (CDCl3): 3575, 3465, 2960, 2935, 2875, 2860, 1715, 1465, 1460, 1385, 1360, 1235, 1130, 1090, 935, 910, 885 cm-1. Anal. Calcd for C8H16O3 (160.2): C, 59.97; H, 10.07. Found: C, 59.68; H, 10.09.

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Confer ref. 18a for a different rationalization.

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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 (δA = 1.69, δB = 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 × mc, 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 Cquat]: 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.