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.

Key words

tetrahydropyran - dactylolide - zampanolide - hydroxy­ynone - alkyne

References and Notes

• 1 Tanaka J. Higa T. Tetrahedron Lett.  1996,  37:  5535 
• 2 Cutignano A. Bruno I. Bifulco G. Casapullo A. Debitus C. Gomez-Paloma L. Riccio R. Eur. J. Org. Chem.  2001,  775 
• 3 Field JJ. Singh AJ. Kanakkaanthara A. Halafihi T. Northcote PT. Miller JH. J. Med. Chem.  2009,  52:  7328 
• 4 Ding F. Jennings MP. J. Org. Chem.  2008,  73:  5965 
• 5 Smith AB. Safonov IG. Corbett RM. J. Am. Chem. Soc.  2001,  123:  12426 
• 6a Smith AB. Safonov IG. Corbett RM. J. Am. Chem. Soc.  2002,  124:  11102 
• 6b Smith AB. Safonov IG. Org. Lett.  2002,  4:  635 
• 6c Hoye TR. Hu M. J. Am. Chem. Soc.  2003,  125:  9576 
• 6d Ding F. Jennings MP. Org. Lett.  2005,  7:  2321 
• 6e Sanchez CC. Keck GE. Org. Lett.  2005,  7:  3053 
• 6f Aubele DL. Wan S. Floreancig PE. Angew. Chem. Int. Ed.  2005,  44:  3485 
• 6g Louis I. Hungerford NL. Humphries EJ. McLeod MD. Org. Lett.  2006,  8:  1117 
• 6h Uenishi J. Iwamoto T. Tanaka J. Org. Lett.  2009,  11:  3262 
• 6i Sharif E. O’Doherty GA. Chemtracts  2009,  22:  67 
• 7a Loh T. Yang J. Feng L. Zhou Y. Tetrahedron Lett.  2002,  43:  7193 
• 7b Troast DM. Yuan J. Porco JA. Adv. Synth. Catal.  2008,  1701 
• 7c Smitha AB. Fox RJ. Razler TM. Acc. Chem. Res.  2008,  41:  675 
• 8a Reddy CR. Rao NN. Tetrahedron Lett.  2009,  50:  2478 
• 8b Reddy CR. Dharmapuri G. Rao NN. Org. Lett.  2009,  11:  5730 
• 8c Reddy CR. Rao NN. Srikanth B. Eur. J. Org. Chem.  2010,  345 
• 9 Shioiri T. McFarlane N. Hamada Y. Heterocycles  1998,  47:  73 
• 10a Wang C. Forsyth CJ. Org. Lett.  2006,  8:  2997 
• 10b Nicolaou KC. Cole KP. Frederick MO. Aversa RJ. Denton RM. Angew. Chem. Int. Ed.  2007,  46:  8875 
• 10c Nicolaou KC. Frederick MO. Burtoloso ACB. Denton RM. Rivas F. Cole KP. Aversa RJ. Gibe R. Umezawa T. Suzuki T. J. Am. Chem. Soc.  2008,  130:  7466 
• 11 Griggs ND. Phillips AJ. Org. Lett.  2008,  10:  4955 
• 12 Yoshinari T. Ohmori K. Schrems MG. Pfaltz A. Suzuki K. Angew. Chem. Int. Ed.  2010,  49:  881 

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): 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.