Stereoselective Synthesis of (–)-Heliannuol E by α-Selective ­Propargyl Substitution

Abstract

This paper describes a stereoselective synthesis of (–)-heliannuol E through intramolecular cyclization of a phenol mesylate. The introduction of the aromatic group was achieved by α-selective propargyl substitution of a propargylic phosphate.

Key words

heliannuol E - propargyl substitution - stereoselectivity - asymmetric synthesis - intramolecular cyclization

Publication History

Received: 10 September 2021

Accepted after revision: 28 September 2021

Article published online:
19 October 2021

• References and Notes

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• 11 The reaction of 35 with TBSCl resulted only in production of compound 36, and the disilyl ether was not formed. The regioisomer was not formed because of steric hindrance.
• 12 (–)-Heliannuol E (5) K₂CO₃ (73.9 mg, 0.535 mmol) was added to an ice-cold solution of olefin 36 (58.3 mg, 0.127 mmol) in MeOH (10 mL). The mixture was stirred at 0 °C for 1 h, then heated and stirred at 45 °C for 15 h. The mixture was then diluted with 3 N aq HCl to pH 5–6 and extracted with Et₂O (×3). The combined extracts were dried (MgSO₄) and concentrated. The residue was purified by recycling HPLC [LC-Forte/R equipped with YMC-Pack SIL-60, hexane–EtOAc (4:1), 25 mL/min] to give a colorless oil; yield: 22.7 mg (67%); R_f = 0.33 (hexane–EtOAc, 3:1); [α]_D ²⁶ –69 (c 0.33, CHCl₃) [Lit.³ –68.6 (c 0.1, CHCl₃)]. IR (neat): 3379, 1635, 1196 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.24 (s, 3 H), 1.30 (s, 3 H), 1.82–1.97 (m, 2 H), 2.20 (s, 3 H), 2.33–2.38 (br s, 1 H), 3.43–3.52 (m, 1 H), 3.74 (dd, J = 10.4, 3.6 Hz, 1 H), 4.35 (s, 1 H), 4.91 (dd, J = 16.8, 1.6 Hz, 1 H), 5.11 (dd, J = 10.4, 1.6 Hz, 1 H), 6.08 (ddd, J = 16.8, 10.4, 6.4 Hz, 1 H), 6.49 (s, 1 H), 6.66 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 15.8, 24.3, 26.0, 27.6, 38.0, 72.1, 77.6, 115.9, 116.0, 118.6, 120.7, 124.2, 142.2, 147.5, 148.3. HRMS (FD): m/z [M]⁺ calcd for C₁₅H₂₀O₃: 248.14124; found: 248.14106.