Toward a New Palmerolide Assembly Strategy: Synthesis of C16–C24

Abstract

Asymmetric synthesis of C16–C24 of palmerolide A is described, featuring convergent Negishi coupling, Singaram propargylation, and successful tactical maneuvering to address an unexpected allylic substitution reaction.

Key words

palmerolide - stereoselective synthesis - coupling - natural products - asymmetric catalysis

• References and Notes

• 1 Current address: Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA

Total syntheses:
• 2a Jiang X, Liu B, Lebreton S, De Brabander JK. J. Am. Chem. Soc. 2007; 129: 6386
• 2b Nicolaou KC, Guduru R, Sun Y.-P, Banerji B, Chen DY.-K. Angew. Chem. Int. Ed. 2007; 46: 5896
• 2c Penner M, Rauniyar V, Kaspar LT, Hall DG. J. Am. Chem. Soc. 2009; 131: 14216

Formal syntheses:
• 3a Jaegel J, Maier ME. Synthesis 2009; 2881
• 3b Gowrisankar P, Pujari SA, Kaliappan KP. Chem. Eur. J. 2010; 16: 5858
• 3c Prasad KR, Pawar AB. Org. Lett. 2011; 13: 4252
• 3d Pujari SA, Gowrisankar P, Kaliappan KP. Chem. Asian J. 2011; 6: 3137

Synthetic approaches:
• 4a Kaliappan KP, Gowrisankar P. Synlett 2007; 1537
• 4b Chandrasekhar S, Vijeender K, Chandrashekar G, Reddy CR. Tetrahedron: Asymmetry 2007; 18: 2473
• 4c Jaegel J, Schmauder A, Binanzer M, Maier ME. Tetrahedron 2007; 63: 13006
• 4d Cantagrel G, Meyer C, Cossy J. Synlett 2007; 2983
• 4e Lebar MD, Baker BJ. Tetrahedron 2010; 66: 1557
• 4f Jones DM, Dudley GB. Synlett 2010; 223
• 4g Prasad KR, Pawar AB. Synlett 2010; 1093
• 5 In addition to the geographical barriers to harvesting in Antarctica, the Antarctic Treaty prohibits exploitation of South Pole resources for commercial gain. Information available through the Antarctic Treaty Secretariat: http://www.ats.aq
• 6a Diyabalange T, Amsler CD, McClintock JB, Baker BJ. J. Am. Chem. Soc. 2006; 128: 5630
• 6b Lebar MD, Baker BJ. Tetrahedron Lett. 2007; 48: 8009
• 6c Riesenfeld CS, Murray AE, Baker BJ. J. Nat. Prod. 2008; 71: 1812
• 7 Noguez JH, Diyabalanage TK. K, Miyata Y, Xie X.-S, Valeriote FA, Amsler CD, McClintock JB, Baker BJ. Bioorg. Med. Chem. 2011; 19: 6608
• 8a Nicolaou KC, Sun Y.-P, Guduru R, Banerji B, Chen DY.-K. J. Am. Chem. Soc. 2008; 130: 3633
• 8b Nicolaou KC, Leung GY. C, Dethe DH, Guduru R, Sun Y.-P, Lim CS, Chen DY.-K. J. Am. Chem. Soc. 2008; 130: 10019
• 8c Ravu VR, Leung GY. C, Lim CS, Ng SY, Sum RJ, Chen DY.-K. Eur. J. Org. Chem. 2011; 463
• 9a Kinghorn AD, Chin Y.-W, Swanson SM. Curr. Opin. Drug Discov. Devel. 2009; 12: 189
• 9b Dalby SM, Paterson I. Curr. Opin. Drug Discov. Devel. 2010; 13: 777
• 10a Kamijo S, Dudley GB. J. Am. Chem. Soc. 2005; 127: 5028
• 10b Kamijo S, Dudley GB. Org. Lett. 2006; 8: 175
• 10c Jones DM, Kamijo S, Dudley GB. Synlett 2006; 936
• 10d Kamijo S, Dudley GB. J. Am. Chem. Soc. 2006; 128: 6499
• 10e Kamijo S, Dudley GB. Tetrahedron Lett. 2006; 47: 5629
• 10f Tummatorn J, Dudley GB. J. Am. Chem. Soc. 2008; 130: 5050
• 10g Jones DM, Lisboa MP, Kamijo S, Dudley GB. J. Org. Chem. 2010; 75: 3260
• 10h Jones DM, Dudley GB. Tetrahedron 2010; 66: 4860
• 10i Tummatorn J, Dudley GB. Org. Lett. 2011; 13: 158
• 10j Tummatorn J, Dudley GB. Org. Lett. 2011; 13: 1572
• 10k Lisboa MP, Hoang TT, Dudley GB. Org. Synth. 2011; 88: 353
• 11 King AO, Okukado N, Negishi EI. J. Chem. Soc., Chem. Commun. 1977; 683
• 12 Cheon C.-G, Kim W.-S, Smith AB. III. Org. Lett. 2005; 7: 3569
• 13 Sun B, Xu X. Tetrahedron Lett. 2005; 46: 8431
• 14 Eliel EL, Wilen SH, Mander LN. Stereochemistry of Organic Compounds. John Wiley and Sons; New York, NY: 1994
• 15a Hirayama LC, Dunham KK, Singaram B. Tetrahedron Lett. 2006; 47: 5173
• 15b For previous application in synthesis, see: Francais A, Leyva A, Etxebarria-J G, Ley SV. Org. Lett. 2010; 12: 340
• 16a Van Horn DE, Negishi E. J. Am. Chem. Soc. 1978; 100: 2252
• 16b Wipf P, Lim S. Angew. Chem., Int. Ed. Engl. 1993; 32: 1068
• 17a Kallan NC, Halcomb RL. Org. Lett. 2000; 2: 2687
• 17b Romero-Ortega M, Colby DA, Olivo HF. Tetrahedron Lett. 2002; 43: 6439
• 17c Quéron E, Lett R. Tetrahedron Lett. 2004; 45: 4527
• 18 Procedure and Data for C16–C24 Fragment 2 To a solution of vinyl iodide 14 (20 mg, 0.062 mmol) in CH₂Cl₂ (3 mL) was added imidazole (8 mg, 0.12 mmol) and TBSCl (11 mg, 0.074 mmol) at r.t. The reaction mixture was stirred overnight and quenched with NH₄Cl. The solution was extracted with CH₂Cl₂ (3×) and the solvent evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel (EtOAc–hexanes = 5:95) to yield vinyl iodide 2 as a colorless oil (23 mg, 85%). [α]_D ²⁵ 15.9 (c 5.32, CH₂Cl₂). IR (thin film): 3467 (br), 2954, 2928, 2856, 1462, 1379, 1252, 1050, 832, 773, 666 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 6.00 (d, J = 7.3 Hz, 1 H), 5.32–5.36 (m, 1 H), 4.19 (d, J = 6.2 Hz, 2 H), 3.62–3.68 (m, 1 H), 2.28–2.40 (m, 2 H), 2.12–2.20 (m, 1 H), 1.86 (d, J = 0.9 Hz, 3 H), 1.68–1.78 (m, 2 H), 1.60 (s, 3 H), 1.47 (d, J = 4.1 Hz, 2 H), 0.89 (s, 9 H), 0.84 (d, J = 6.8 Hz, 3 H), 0.06 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 145.3, 135.1, 126.6, 71.3, 60.1, 44.7, 43.5, 35.5, 25.9, 24.0, 18.4, 16.1, 13.3, –5.1. ESI-HRMS: m/z calcd for C₁₈H₃₅O₂ISiNa [M + Na⁺]: 461.1348; found: 461.1343