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Synlett 2003(12): 1813-1816  
DOI: 10.1055/s-2003-41487
LETTER
© Georg Thieme Verlag Stuttgart · New York

Concise Synthesis of Optically Pure syn-1,3-Diols by Stereoselective Desymmetrization of a Divinylcarbinol

Thilo Berkenbusch*a, Reinhard Brückner*b
a Bayer AG, BCH-FCH-RD-LP2, Building G 8, 51368 Leverkusen, Germany
b Institut für Organische Chemie und Biochemie, Albert-Ludwigs-Universität, 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 23 June 2003
Publication Date:
19 September 2003 (online)

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Abstract

Divinylcarbinols 17 and 18, CS-symmetrical and cis-configured, were desymmetrized by Sharpless’ asymmetric epoxidation. This furnished anti-configured monoepoxy alcohols 19 (85% ee) and 20 (94% ee), respectively, or their mirror images (ent-19, 84% ee; ent-20, 95% ee). 20 (ent-20) was reduced by Red-Al® regio- and chemoselectively, providing syn-1,3-diols ent-21 (21) at low and ent-22 (22) at higher temperature (94-95% ee). They should allow the obtention of more elaborated syn-1,3-diols.

Key words

acetonides - desymmetrization - 1,3-diols - epoxyalcohols - Sharpless asymmetric epoxidation

9

Compound 16 has been previously prepared, see ref. [7a]

10

Except for compound 24, all new compounds gave satisfactory 1H NMR and IR spectra as well as correct combustion analyses.

16

This was concluded from the integral ratio of the peaks attributed to 3-H [δmajor = 3.02 (dd; 19/ent-19), δminor = 3.08(dd)].

18

In addition, we retrieved inseparable mixtures of mono- with bis-epoxides.

19

This was concluded from the integral ratio of the peaks attributed to 3-H [δmajor = 3.00 (dd; 20/ent-20), δminor = 3.06(dd)].

20

cis-(2R,3S,4S)-2,3-Epoxy-1,7-bis-[4-methoxybenzyl)oxy]-5-hepten-4-ol(20): [α]D 25 = -30.9 (c = 0.58 in CHCl3);
- 94.4% ee by HPLC.
1H NMR (500.0 MHz, CDCl3): δ = 2.80 (d, J OH,4 = 2.3 Hz, OH), 3.00 (dd, J 3,4 = 7.5 Hz, J 3,2 = 4.3 Hz, 3-H), 3.25 (mc, probably incompletely resolved ddd: J 2,1-H(A) = J 2,1-H(B) =
ca. 5.7 Hz, J 2,3 = 4.3 Hz, 2-H), AB signal (δA = 3.63, δB = 3.79, J AB = 11.1 Hz, in addition split by J A,2 = 6.2 Hz, J B,2 = 5.4 Hz, 1-H2), B part superimposed by 3.80 (s, 2 × OCH3), AB signal (δA = 4.05, δB = 4.11, J AB = 12.9 Hz, in addition split by J A,6 = 5.7 Hz, 4 J A,5-H = 1.4 Hz, J B,6 = 6.7 Hz, 4 J B,5-H = 1.5 Hz, 7-H2), 4.25 (br dd, J 4,3 = J 4,5 = 7.5 Hz, 4-H), 4.42
(s, 1′′-H2)*, AB signal (δA = 4.46, δB = 4.54, J AB = 11.4 Hz,
1′-H2), 5.70 (dddd, J cis = 11.3 Hz, J 5,4 = 7.6 Hz, 4 J 5,7-H(A) = 4 J 5,7-H(B) = 1.5 Hz, 5-H), 5.82 (br ddd, J cis = 11.4 Hz,
J 6,7-H(A) = J 6,7-H(B) = 6.0 Hz, 6-H), AA′BB′ signal centered at δ = 6.88 and δ = 7.26 (2 × C6H4).
13C NMR (125.8 MHz, CDCl3): δ = 54.73 (C-2), 55.26 (2 × OCH3), 58.12 (C-3), 65.80 (C-7), 66.34 (C-4), 68.00 (C-1), 72.02 (C-1′′), 73.20 (C-1′), 113.83, 113.96, 129.46, and 129.60 (2 × 2 × C ortho , 2 × 2 × C meta ), 129.32, 130.03, 159.28, and 159.51 (2 × C para , 2 × C ipso ), 130.29 (C-6), 131.71 (C-5).
IR(film): 3400, 3000, 2935, 2910, 2860, 2835, 1610, 1585, 1515, 1460, 1300, 1250, 1175, 1075, 1035, 850, 820 cm-1.
Anal. Calcd for C23H28O6 (400.5): C, 68.98; H, 7.05. Found C, 68.99; H, 7.20.

22

cis-(2S,4R)-1,7-Bis-[(4-methoxybenzyl)oxy]-5-heptene-2,4-diol (ent-21): [α]D 25 = 14.8 (c = 0.78 in CHCl3).
1H NMR (500.0 MHz, CDCl3): δ = AB signal (δA = 1.55,
δB = 1.71, J AB = 14.2 Hz, in addition split by J A,4 = 4.4 Hz, J A,2 = 2.7 Hz, J B,2 = 9.9 Hz, J B,4 = 8.8 Hz, 3-H2), 3.07 (br s, 2 × OH), AB signal (δA = 3.35, δB = 3.40, J AB = 9.5 Hz, in addition split by J A,2 = 7.1 Hz, J B,2 = 4.1 Hz, 1-H2), 3.795 and 3.804 (2 × s, 2 × OCH3), 3.96 (mc, 2-H), AB signal (δA = 4.06, δB = 4.09, J AB = 12.4 Hz, in addition split by J A,6 = 6.1 Hz, 4 J A,5-H = 1.3 Hz, J B,6 = 6.4 Hz, J B,5-H = 1.3 Hz, 7-H2), AB signal (δA = 4.43, δB = 4.46, J AB = 11.2 Hz, 1′-H2), B part partly superimposed by 4.47 (s, 1′′-H2), 4.67 (ddd with incompletely resolved allylic couplings, J 4,5 = J 4,3-H(B) = 8.4 Hz, J 4,3-H(A) = 4.2 Hz, 4-H), 5.60 (dddd, J cis = 11.4 Hz, J 5,4 = 8.0 Hz, 4 J 5,7-H(A) = 4 J 5,7-H(B) = 1.3 Hz, 5-H), 5.68 (dddd, J cis = 11.2 Hz, J 6,7-H(A) = J 6,7-H(B) = 6.2 Hz, 4 J 6,4 = 0.9 Hz, 6-H), AA′BB′ signal centered at δ = 6.87 and δ = 7.25 (2 × C6H4).
13C NMR (125.7 MHz, CDCl3): δ = 39.74 (C-3), 55.26 (2 × OCH3), 65.54, 67.63, 70.20, 72.19, 73.06 and 74.00 (C-1, C-2, C-4, C-7, C-1′, C-1′′), 113.85, 127.69, 129.40, 129.50, 129.93, 129.97, 135.72, 159.32, and 159.33 (9 resonances for 10 non-equivalent nuclei: C-5, C-6, 2 × C6H4).
IR(film): 3400, 3000, 2920, 2855, 1615, 1585, 1515, 1465, 1455, 1445, 1420, 1360, 1300, 1245, 1175, 1075, 1030, 820 cm-1.
Anal. Calcd for C23H30O6 (402.5): C, 68.64; H, 7.51. Found: C, 68.34; H, 7.24.

24

(2R,4R)-1-[(4-Methoxybenzyl)oxy]-6-heptene-2,4-diol (22): [α]D 25 = -1.9 (c = 0.81 in CHCl3).
1H NMR (500.0 MHz, CDCl3): δ = AB signal (δA = 1.53,
δB = 1.62, J AB = 14.4 Hz, in addition split by J A,2 = J A,4 = 9.8 Hz, J B,2 = J B,4 = 2.7 Hz, 3-H2), 2.25 (dddd, J 5,6 = 7.3 Hz, J 5,4 = 6.2 Hz, 4 J 5,7-H(E) = 4 J 5,7-H(Z) = 1.1 Hz, 5-H2), 2.91-3.28 (m, 2 × OH), AB signal (δA = 3.35, δB = 3.43, J AB = 9.4 Hz, in addition split by J A,2 = 7.1 Hz, J B,2 = 3.9 Hz, 1-H2), 3.81 (s, OCH3), 3.92 (dtd with transition to higher order splitting, J 4,3-H(A) = 9.8 Hz, J 4,5 = 6.1 Hz, J 4,3-H(B) = 2.5 Hz, 4-H), 4.04 (dddd, J 2,3-H(A) = 10.4 Hz, J 2,1-H(A) = 6.6 Hz, J 2,1-H(B) = 3.8 Hz, J 2,3-H(B) = 3.1 Hz, 2-H), 4.48 (s, 1′-H2), 5.09-5.14 (m, 7-H E , 7-H Z ), 5.82 (mc, 6-H), AA′BB′ signal centered at δ = 6.88 and δ = 7.25 (C6H4).
13C NMR (125.7 MHz, CDCl3): δ = 38.71 and 42.21 (C-3, C-5), 55.26 (OCH3), 71.02, 71.16, 73.05, and 73.99 (C-1, C-2, C-4, C-1′), 113.86 and 129.41 (2 × C ortho , 2 × C meta ), 117.86, 129.89, 134.51, and 159.35 (C-6, C-7, C para , C ipso ).
IR(film): 3400, 3075, 2915, 2860, 1640, 1615, 1585, 1515, 1460, 1440, 1365, 1300, 1250, 1175, 1100, 1035, 990, 920, 820 cm-1.
Anal. Calcd for C15H22O4 (266.3): C, 67.64; H, 8.33. Found: C, 67.54; H, 8.39.