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DOI: 10.1055/s-2007-985604
Synthesis of Optically Active δ-Dodecalactone via Chiral Resolution Using CPF
Publikationsverlauf
Publikationsdatum:
23. August 2007 (online)
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Abstract
(R)-6-Heptyltetrahydropyran-2-one and its S-enantiomer were synthesized via chiral resolution of (±)-1-undecen-4-ol by (R)-3a-allyl-3,3a,4,5-tetrahydro-2H-cyclopenta[b]furan (CPF). The R-enantiomer has sophisticated strong, fruity flavor, while the flavor of the S-enantiomer is soft and sweet, similar to apricot.
Key words
chiral resolution - acetals - flavor - alkenyl ethers
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1a
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References and Notes
The synthetic route shown in Scheme [1] was also applicable to all the lactones 1 (n = 3-6).
7The ΔR f value between the isopropyl esters 5a and 5b was as large as those between the corresponding methyl or ethyl esters. Thus, the high efficiency of chiral resolution of 3 is not due to the isopropyl ester moiety. Incidentally, the chemical yield of 3 from lactone 2 (85%) was much higher than the chemical yields of the corresponding methyl or ethyl esters (<8%), probably because reversible reaction from 3 to 2 is much slower than those from the corre-sponding methyl or ethyl esters to 2. This is the reason for the choice of the isopropyl ester.
9TLC equipment was obtained from Merck (1.05715.0009, Silica gel 60F254).
10Although preparations of ca. 30 kg of (R)- and (S)-2 were also carried out in similar manner, it was not a simple batch procedure. Thus, the procedure for a ca. 1-kg scale is described. After isolation and purification, optical rotations of the two enantiomers were measured under new conditions. (R)-2: [α]D 40 +46.9° (c = 1.00, heptane); (S)-2: [α]D 40 -46.4° (c = 1.00, heptane).
13
8a: a colorless oil; [α]D
20 -36.0° (c = 2.765, CHCl3). FTIR: 3074, 2927, 1639, 1434 cm-1. 1H NMR (400 MHz, CDCl3): δ = 5.76-5.91 (m, 2 H), 5.00-5.07 (m, 4 H), 3.75-3.84 (m, 3 H), 2.16-2.28 (m, 3 H), 2.04-2.09 (m, 2 H), 1.93 (ddd, J = 5.2, 6.8, 12.0 Hz, 1 H), 1.68 (dt, J = 7.6, 12.0 Hz, 1 H), 1.48-1.62 (m, 8 H), 1.24-1.31 (m, 9 H), 0.88 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 136.9 (CH), 135.7 (CH), 117.6 (CH2), 116.5 (C), 73.2 (CH), 65.9 (CH2), 54.6 (C), 40.6 (CH2), 39.8 (CH2), 38.4 (CH2), 36.5 (CH2), 35.6 (CH2), 35.3 (CH2), 31.9 (CH2), 29.9 (CH2), 29.4 (CH2), 25.1 (CH2), 22.8 (CH2), 21.6 (CH2), 14.2 (CH3). EI-MS: m/z = 321 [M + 1]+. HRMS (EI): m/z calcd for C21H36O2: 320.2715; found: 320.2714.
8b: a colorless oil; [α]D
20 -6.7° (c = 4.17, CHCl3). FTIR: 3074, 2932, 1639, 1434 cm-1. 1H NMR (400 MHz, CDCl3): δ = 5.78-5.90 (m, 2 H), 4.98-5.06 (m, 4 H), 3.71-3.80 (m, 3 H), 2.32 (t, J = 6.0 Hz, 2 H), 2.25 (dd, J = 6.4, 13.6 Hz, 1 H), 2.03-2.10 (m, 2 H), 1.92 (dt, J = 6.0, 12.4 Hz, 1 H), 1.66 (dt, J = 7.6, 12.0 Hz, 1 H), 1.38-1.63 (m, 8 H), 1.24-1.31 (m, 9 H), 0.88 (t, J = 6.4 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 136.9 (CH), 135.6 (CH), 117.8 (CH2), 116.5 (C), 73.4 (CH), 65.7 (CH2), 54.6 (C), 40.6 (CH2), 40.5 (CH2), 38.4 (CH2), 36.7 (CH2), 35.1 (CH2), 34.8 (CH2), 31.9 (CH2), 29.8 (CH2), 29.4 (CH2), 25.6 (CH2), 22.7 (CH2), 21.6 (CH2), 14.2 (Me). EI-MS: m/z = 321 [M + 1]+. HRMS (EI): m/z calcd for C21H36O2: 320.2715; found: 320.2691.
(
S
)-9: [α]D
20 -10.8° (c = 1.56, CHCl3). FTIR: 3076, 2928, 2857, 1640, 1460 cm-
1. 1H NMR (400 MHz, CDCl3): δ = 5.77-5.87 (m, 1 H), 5.00-5.05 (m, 2 H), 3.65-3.71 (m, 1 H), 2.18-2.23 (m, 2 H), 1.29-1.41 (m, 15 H), 0.89 (s, 9 H), 0.05 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 135.5 (CH), 116.5 (CH2), 72.1 (CH), 42.0 (CH2), 36.9 (CH2), 31.9 (CH2), 29.8 (CH2), 29.4 (CH2), 26.0 (CH2), 25.4 (CH2), 22.7 (CH2), 18.3 (C), 14.2 (Me), -4.2 (Me), -4.4 (Me). EI-MS: m/z = 285 [M + 1]+. HRMS (EI): m/z calcd for C17H36OSi: 284.2535; found: 284.2543.
(
R
)-9: [α]D
20 +10.1° (c = 1.64, CHCl3). FTIR: 3076, 2930, 1642, 1462 cm-
1. 1H NMR (400 MHz, CDCl3): δ = 5.77-5.87 (m, 1 H), 5.00-5.05 (m, 2 H), 3.65-3.71 (m, 1 H), 2.18-2.23 (m, 2 H), 1.29-1.41 (m, 15 H), 0.89 (s, 9 H), 0.05 (s, 6 H). 13C NMR (100 MHz, CDCl3): δ = 135.5 (CH), 116.5 (CH2), 72.1 (CH), 42.0 (CH2), 36.9 (CH2), 31.9 (CH2), 29.8 (CH2), 29.4 (CH2), 26.0 (CH2), 25.4 (CH2), 22.7 (CH2), 18.3 (C), 14.2 (Me), -4.2 (Me), -4.4 (Me). EI-MS: m/z = 283 [M - 1]+. HRMS (EI): m/z calcd for C17H36OSi: 284.2535; found: 284.2529.
(
S
)-10: colorless oil; [α]D
20 +2.4° (c = 1.56, CHCl3). FTIR: 3054, 2928, 2856, 2719, 1727, 1470 cm-
1. 1H NMR (400 MHz, CDCl3): δ = 9.82 (s, 1 H), 4.15-4.20 (m, 1 H), 2.51-2.52 (m, 2 H), 1.51-1.53 (m, 2 H), 1.20-1.37 (m, 10 H), 0.88 (s, 12 H), 0.08 (s, 3 H), 0.06 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 202.3 (CH), 68.3 (CH), 50.9 (CH2), 37.9 (CH2), 31.8 (CH2), 29.6 (CH2), 29.3 (CH2), 25.8 (3 × Me), 25.2 (CH2), 22.7 (CH2), 18.1 (C), 14.2 (Me), -4.3 (Me), -4.6 (Me). EI-MS: m/z = 286 [M]+. HRMS (EI): m/z calcd for C16H34O2Si: 286.2328; found: 286.2321.
(
R
)-10: [α]D
20 -2.2° (c = 2.42, CHCl3). FTIR: 3054, 2930, 2720, 1728, 1585, 1470 cm-
1. 1H NMR (400 MHz, CDCl3): δ = 9.82 (s, 1 H), 4.15-4.20 (m, 1 H), 2.51-2.52 (m, 2 H), 1.51-1.53 (m, 2 H), 1.20-1.37 (m, 10 H), 0.88 (s, 12 H), 0.08 (s, 3 H), 0.06 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 202.3 (CH), 68.3 (CH), 50.9 (CH2), 37.9 (CH2), 31.8 (CH2), 29.6 (CH2), 29.3 (CH2), 25.8 (3 × Me), 25.2 (CH2), 22.7 (CH2), 18.1 (C), 14.2 (Me), -4.3 (Me), -4.6 (Me). EI-MS: m/z = 287 [M + 1]+. HRMS (EI): m/z calcd for C16H34O2Si: 286.2328; found: 286.2325.
It is well known that compounds bearing a hydroxyl group at an asymmetric allylic or benzylic position can be separated more efficiently than saturated aliphatic alcohols when using most of the other chiral resolving agents. CPF has a similar tendency as described above. However, our investigations have shown that the separation efficiency of CPF is much greater than that of other agents. Chiral resolution of both 3 and 7 was successful and efficient, and we know no other reason for this high efficiency.