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Synlett 2010(10): 1536-1538  
DOI: 10.1055/s-0029-1219931
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Ch. Raji Reddy*, B. Srikanth
Organic Division - I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax: +91(40)27160512; e-Mail: rajireddy@iict.res.in;
Further Information

Publication History

Received 6 March 2010
Publication Date:
10 May 2010 (online)

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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.

Key words

tetrahydropyran - dactylolide - zampanolide - hydroxy­ynone - alkyne

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13

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): νmax = 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): νmax = 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): νmax = 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): νmax = 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.