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DOI: 10.1055/s-2003-41487
Concise Synthesis of Optically Pure syn-1,3-Diols by Stereoselective Desymmetrization of a Divinylcarbinol
Publication History
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
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References
Compound 16 has been previously prepared, see ref. [7a]
10Except for compound 24, all new compounds gave satisfactory 1H NMR and IR spectra as well as correct combustion analyses.
16This was concluded from the integral ratio of the peaks attributed to 3-H [δmajor = 3.02 (dd; 19/ent-19), δminor = 3.08(dd)].
18In addition, we retrieved inseparable mixtures of mono- with bis-epoxides.
19This 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.
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.
(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.