Tetrahydrofuran Ring Construction through Tandem Iodocyclizations: Synthesis of Hagen’s Gland Lactones, a Pheromone of Idea leuconoe, an Oxylipid, and Related Compounds

Dedicated to Professor Richard R. Schmidt on the occasion of his 90^th birthday

Abstract

A simple and efficient common route was developed for the syntheses of tetrahydrofuran-ring-containing natural products such as Hagen’s gland lactones and their epimers, a pheromone of the butterfly Idea leuconoe, an oxylipid, and some valuable synthons. Brown’s allylation, cross-metathesis, iodocyclization, and a tandem aminoxylation/allylation were employed as key steps in the syntheses.

Key words

tetrahydrofurans - iodocyclization - Hagen’s gland lactone - oxylipids - pheromones - cross-metathesis

Publication History

Received: 30 January 2025

Accepted after revision: 03 March 2025

Accepted Manuscript online:
03 March 2025

Article published online:
10 April 2025

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• 20 (3aR,5R,6aR)-5-Butyltetrahydrofuro[3,2-b]furan-2(3H)-one (1) NaHCO₃ (135 mg, 1.61 mmol, 3.0 equiv) and I₂ (204 mg, 1.61 mmol, 3.0 equiv) were sequentially added to a solution of 13a (100 mg, 0.54 mmol) in MeCN (10 mL) at 0 °C, and the mixture was stirred for 6 h then cooled to rt. The reaction was quenched with aq Na₂S₂O₃, and the aqueous layer was extracted with EtOAc (2 × 5 mL). The combined organic layers were washed with H₂O and brine, dried (Na₂SO₄), and concentrated. The residue was purified by column chromatography [silica gel, PE–EtOAc (85:15)] to give a colorless oil; yield: 82.1 mg (83%). [Further elution (PE–EtOAc, 84:16) gave the epimer 3; yield: 6.9 mg (7%)]; [α]_D ²⁵ +49.5 (c 1.0, CHCl₃) [Lit.^5g +50.9 (c 1.0, CHCl₃)]. IR (neat): 2930, 2864, 1781, 1459, 1345, 1180, 1065 cm^–1. ¹H NMR (200 MHz, CDCl₃): δ = 5.13 (t, J = 4.7 Hz, 1 H), 4.84–4.79 (m, 1 H), 4.07 (dt, J = 6.3, 10.8 Hz, 1 H), 2.77 (dd, J = 6.6, 18.8 Hz, 1 H), 2.65 (d, J = 18.6 Hz, 1 H), 2.38 (dd, J = 4.6, 13.7 Hz, 1 H), 1.71–1.65 (m, 1 H), 1.57–1.43 (m, 2 H), 1.43–1.29 (m, 4 H), 0.90 (t, J = 7.0 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 176.1, 84.9, 78.2, 77.3, 38.8, 36.6, 34.3, 28.1, 22.6, 13.9. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₀H₁₆NaO₃: 207.0992; found: 207.0994.