Enantioselective Formal Total Synthesis of Damsin

Abstract

Enantioselective formal total synthesis of damsin, which was isolated from Compositae Ambrosia maritima L., is described. The highly enantio- and diastereoselective catalytic Mukaiyama–Michael reaction and subsequent highly stereoselective epimerization shorten the synthetic steps. It is also reported that the enolate, which was formed by the reaction of β-keto sulfone with lithium naphthalenide, reacted with methyl cyanoformate to form a quaternary stereogenic center in high yield with high stereoselectivity. This finding extends the synthetic chemistry starting from β-keto sulfones.

Key words

asymmetric catalysis - enantioselective - Mukaiyama–­Michael reaction - stereoselective - total synthesis - damsin - pseudoguaianolides

Publikationsverlauf

Eingereicht: 20. Dezember 2022

Angenommen nach Revision: 20. Januar 2023

Accepted Manuscript online:
20. Januar 2023

Artikel online veröffentlicht:
15. Februar 2023

• References and Notes

• 1 Shady H.-A, Soine TO. J. Am. Pharm. Assoc. 1953; 42: 387
• 2a Suchy M, Herout V, Sorm F. Collect. Czech. Commun. 1963; 28: 2257
• 2b Doskotch RW, Hufford CD. J. Pharm. Sci. 1969; 58: 186
• 3a Fischer NH, Olivier EG, Fischer HD. Fortschr. Chem. Org. Naturst. 1979; 38: 47
• 3b Seaman FC. Bot. Rev. 1982; 48: 121
• 4a Doskotch RW, Hufford CD. J. Pharm. Sci. 1969; 58: 186
• 4b Lee K, Huang E, Plantadosl C, Pagano JS, Geissman TA. Cancer Res. 1971; 31: 1649
• 4c Villagomez R, Collado JA, Muñoz E, Almanza G, Sterner O. J. Biomed. Sci. Eng. 2014; 7: 833
• 4d Svensson D, Lozano M, Almanza GR, Nilsson B.-O, Sterner O, Villagomez R. Phytomedicine 2018; 50: 118
• 5a Kretchmer R, Thompson WJ. J. Am. Chem. Soc. 1976; 98: 3379
• 5b De Clercq P, Vandewalle M. J. Org. Chem. 1977; 42: 3447
• 5c Greico PA, Ohfune Y, Majetich G. J. Am. Chem. Soc. 1977; 99: 7393
• 5d Quallich GJ, Schlessinger RH. J. Am. Chem. Soc. 1979; 101: 7627
• 5e Money T, Wong MK. C. Tetrahedron 1996; 52: 6307

For a review, see:
• 5f Barbero M, Prandi C. Nat. Prod. Commun. 2018; 13: 241
• 6 Sugiyama R, Nakada M. Synlett 2023; 34 in press, DOI:
• 7 In a small scale, used ligand could be removed by extraction using 1 M HCl.
• 8 Takeda H, Watanabe H, Nakada M. Tetrahedron 2006; 62: 8054
• 9 Uwamori M, Osada R, Sugiyama R, Nagatani K, Nakada M. J. Am. Chem. Soc. 2020; 142: 5556
• 10 Compound 13 – Procedure To a stirred solution of naphthalene (837 mg, 6.53 mmol) in THF (21.8 mL) was added Li (45.9 mg, 6.61 mmol) at room temperature. After 6 h, the resulting mixture was added to 12 (318 mg, 1.09 mmol) in THF (5.44 mL) at –78 ℃. After stirring the mixture at the same temperature for 10 min, NCCO₂Me (0.432 mL, 5.44 mmol) was added to the mixture at the same temperature. The mixture was stirred at –78 ℃ for 70 min and then quenched with saturated aqueous NaHCO₃ solution (10 mL). The aqueous layer was extracted with ethyl acetate (3 × 20 mL). The combined organic layer was washed with brine (30 mL), dried over Na₂SO₄, filtered, and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography (hexane/ethyl acetate = 20/1) to afford 13 (206 mg, 90%) as a colorless oil: R_f = 0.64 (hexane/ethyl acetate = 2/1). ¹H NMR (500 MHz, CDCl₃): δ = 5.66 (ddd, J = 16.0, 10.0, 7.5 Hz, 1 H), 5.03 (d, J = 16.0 Hz, 1 H),4.99 (d, J = 10.0 Hz, 1 H), 3.72 (s, 3 H), 2.58 (ddd, J = 11.0, 11.0, 6.5 Hz, 1 H), 2.46–2.30 (m, 2 H), 2.19–2.08 (m, 2 H), 1.47 (dddd, J = 12.5, 12.5, 12.5, 8.5 Hz, 1 H), 1.23 (s, 3 H), 0.92 (d, J = 6.5 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 216.0, 173.7, 142.0, 114.3, 59.4, 52.6, 50.1, 40.0, 37.6, 25.5, 18.9, 12.9. HRMS (ESI): m/z [M+Na⁺] calcd for C₁₂H₁₈NaO₃: 233.1154; found: 233.1149; [α]_D ²¹ +77 (c 0.12, CH₂Cl₂).
• 11 Noyori R, Murata S, Suzuki M. Tetrahedron 1981; 37: 3899
• 12 Blanchette MA, Choy W, Davis JT, Essenfeld AP, Masamune S, Roush WR, Sakai T. Tetrahedron Lett. 1984; 25: 2183
• 13 ¹H NMR of the mixture indicated that the mixture contained α,β- and β,γ-unsaturated butenolide in a ratio of 1.5:1.
• 14 Money’s enantioselective formal total synthesis required 36 steps from (–)-camphor to reach damsin.