An Approach to Benzannelated [5,6]-Spiroketals

Abstract

Heating a variety of 2-hydroxybenzyl acetates bearing a range functional groups on the 4- or 5-position of the aromatic ring at 100 ˚C in neat γ-methylene-γ-butyrolactone (1.0 M) for 20 hours gives a series of benzannelated [5,6]-spiroketals in 75-89% yield.

Diels-Alder reactions - spiro compounds - heterocycles - natural products - ortho-quinone methide

References and Notes

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10

General Procedure: 2-Hydroxybenzyl acetate (8a; 40 mg, 0.24 mmol) in γ-methylene-γ-butyrolactone (0.24 mL,
1.0 M) was heated at 100 ˚C for 20 h. The cooled reaction mixture was purified by flash column chromatography (SiO₂, 25% → 30% EtOAc in PE) to give 9a as a white solid (36 mg, 84%); mp 107-108 ºC (lit.^¹² 106 ºC); R _f 0.26 (EtOAc-PE, 3:7). IR: 2961, 2920, 1776 (C=O), 1582, 1489, 1447, 1251, 1220, 1170, 1093, 1055 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.07-7.17 (m, 2 H, 2 × ArCH), 6.93 (dt, J = 7.4, 1.1 Hz, 1 H, ArCH), 6.81 (dd, J = 8.1, 1.1 Hz, 1 H, ArCH), 3.06-3.18 (m, 1 H, 1 H of CH₂), 2.91-3.04 (m, 1 H, 1 H of CH₂), 2.79 (ddd, J = 16.5, 6.0, 2.5 Hz, 1 H, 1 H of CH₂), 2.64 (ddd, J = 17.6, 9.5, 2.5 Hz, 1 H, 1 H of CH₂), 2.52 (ddd, J = 13.1, 9.5, 2.5 Hz, 1 H, 1 H of CH₂), 2.19-2.35 (m, 2 H, 2 × 1 H of CH₂), 2.06-2.16 (m, 1 H, 1 H of CH₂). ^¹³C NMR (100 MHz, CDCl₃): δ = 175.5 (C=O), 151.4 (ArCO), 129.0 (ArCH), 127.5 (ArCH), 121.6 (ArCH), 120.9 (ArC), 116.7 (ArCH), 106.2 (OCO), 33.8 (CH₂), 30.1 (CH₂), 28.2 (CH₂), 21.4 (CH₂). HRMS (EI): m/z [M + Na]⁺ calcd for C₁₂H₁₂O₃Na: 227.0684; found: 227.0690.

11 These were generally prepared in good yield by selective primary acetylation of the corresponding 2-hydroxybenzyl alcohols using Ac₂O (1.05 equiv) in the presence of catalytic BF₃˙OEt₂ (5 mol%), see: Weinert EE. Frankenfield KN. Rokita SE. Chem. Res. Toxicol.  2005,  18:  1364 

12 Mixich Z. Monatsh. Chem.  1965,  96:  220