Synthesis of the Tetrahydropyran Subunit (C8-C20 Fragment) of (-)-Dactylolide and (-)-Zampanolide

Abstract

The asymmetric synthesis of the tetrahydropyran containing C8-C20 fragment, a common key subunit of both (-)-dactyl­olide and (-)-zampanolide, is described. The salient feature of this synthesis is the extension of carbon chains using alkynols followed by the use of an alkyne system to generate the desired functionalities, in particular formation of the embedded pyran via an intramolecular oxa-Michael addition of a β-hydroxyynone.

tetrahydropyran - dactylolide - zampanolide - hydroxy­ynone - alkyne

References and Notes

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Spectral Data for Representative Compounds
( S )-8-(Benzyloxy)-1-( tert -butyldiphenylsilyloxy)-2-hydroxyoct-5-yn-4-one (8)
[α]_D ^³¹ -8.5 (c 1.0, CHCl₃). IR (KBr): ν_max = 3442, 2929, 2215, 1670, 1426, 1110, 822, 703 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.65-7.59 (m, 4 H), 7.43-7.21 (m, 11 H), 4.53 (s, 2 H), 4.25-4.16 (m, 1 H), 3.60 (t, J = 2.9 Hz, 2 H), 3.60 (td, J = 10.9, 5.1 Hz, 2 H), 2.74-2.71 (m, 2 H), 2.65 (t, J = 6.5 Hz, 2 H), 2.03 (br s, 1 H), 1.06 (s, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 186.0, 137.6, 135.4, 132.9, 129.8, 128.4, 127.7, 127.6, 91.6, 81.4, 73.0, 68.0, 67.0, 66.8, 48.7, 26.8, 20.4, 19.1. ESI-HRMS: m/z calcd for C₃₁H₃₆NaO₄Si: 523.2306 [M + Na]⁺; found: 523.2295.
(2 S ,6 S )-2-[2-(Benzyloxy)ethyl]-6-[( tert -butyldiphenyl-silyloxy)methyl]dihydro-2 H -pyran-4 (3 H )-one (10) [α]_D ^²7 -10 (c 1.0, CHCl₃). IR (KBr): ν_max = 2928, 2858, 1640, 1463, 1426, 1363, 1111, 701 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 7.64 (td, J = 7.5, 1.3 Hz, 4 H), 7.44-7.17 (m, 11 H), 4.46 (AB, J = 12.2 Hz 1 H), 4.41 (AB, J = 12.2 Hz, 1 H), 3.83-3.49 (m, 6 H), 2.35 (dd, J = 14.1, 4.5 Hz, 3 H), 2.20 (ddd, J = 14.1, 11.5, 4.5 Hz, 1 H), 1.95-1.73 (m, 2 H), 1.02 (s, 9 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 207.3, 135.6, 135.5, 133.3, 133.2, 129.6, 128.3, 127.6, 127.5, 77.0, 73.9, 73.0, 66.3, 66.0, 47.7, 44.0, 36.4, 26.7, 19.2. ESI-HRMS: m/z calcd for C₃₁H₃₈NaO₄Si: 525.2437 [M + Na]⁺; found: 525.2443.
( E )-6-[(2 S ,6 S )-6-Allyl-4-methylenetetrahydro-2 H -pyran-2-yl]-5-methylhex-5-en-2-yn-1-ol (16) [α]_D ^²8 -15.3 (c 0.5, CHCl₃). IR (KBr): ν_max = 3458, 2932, 2853, 2325, 1647, 1427, 1219, 1015, 893, 771 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 5.91-5.74 (m, 1 H), 5.48 (dq, J = 7.1, 1.1 Hz, 1 H), 5.12-5.08 (m, 1 H), 5.08-5.01 (m, 1 H), 4.71 (t, J = 1.5 Hz, 2 H), 4.26 (s, 2 H), 4.00 (ddd, J = 10.9, 7.9, 2.8 Hz, 1 H), 3.41-3.30 (m, 1 H), 2.93 (s, 2 H), 2.45-2.32 (m, 1 H), 2.29-2.12 (m, 3 H), 2.06 (t, J = 12.8 Hz, 1 H), 1.93 (t, J = 12.8 Hz, 1 H), 1.58 (br s, 1 H), 1.75 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 143.8, 134.0, 133.3, 126.4, 116.5, 108.3, 82.6, 80.4, 76.1, 75.1, 50.9, 40.2, 39.4, 29.2, 28.3, 16.4. ESI-HRMS: m/z calcd for C₁₆H₂₂NaO₂: 269.1512 [M + Na]⁺; found: 269.151.
[(2 R ,3 R )-3-{( E )-3-[(2 S ,6 S )-6-Allyl-4-methylene-tetrahydro-2 H -pyran-2-yl]-2-methylallyl}oxiran-2-yl]-methanol (5)
[α]_D ^²7 -15.5 (c 1.0, CH₂Cl₂). IR (KBr): ν_max = 3425, 3074, 2980, 2937, 2896, 1649, 1433 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 5.92-5.70 (m, 1 H), 5.34 (dq, J = 7.7, 1.0 Hz, 1 H), 5.14-5.10 (m, 1 H), 5.09-5.02 (m, 1 H), 4.74 (t, J = 1.5 Hz, 2 H), 4.04 (ddd, J = 10.8, 7.7, 2.6 Hz, 1 H), 3.98-3.88 (m, 1 H), 3.71-3.60 (m, 1 H), 3.43-3.32 (m, 1 H), 3.07 (ddd, J = 5.6, 5.6, 2.2 Hz, 1 H), 2.97-2.93 (m, 1 H), 2.41 (dd, J = 14.1, 6.2 Hz, 1 H), 2.33 (dd, J = 14.5, 6.0 Hz, 1 H), 2.28-2.14 (m, 4 H), 2.05 (t, J = 12.6 Hz, 1 H), 1.93 (t, J = 12.6 Hz, 1 H), 1.76 (d, J = 1.1 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 144.2, 135.0, 134.4, 128.0, 116.9, 108.7, 77.7, 75.4, 61.4, 58.2, 54.5, 41.5, 40.7, 40.6, 39.8, 17.3. ESI-HRMS: m/z calcd for C₁₆H₂₄NaO₃: 287.1618 [M + Na]⁺; found: 287.1626.