Mechanistic Investigation of a Novel Medium-Sized Ring Rearrangement

Abstract

The dominant mechanism operating in a recently disclosed ring contraction is revealed for the first time. New insight and supporting evidence into a classic ring-contraction strategy within a rigidified larger ring system are provided.

Key words

Favorskii rearrangement - mechanism - medium-sized ring - ¹⁸O labelling - rearrangement - ring contraction - semi-benzylic

• References and Notes

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• 14 Typical Procedure To a solution of 1 (10 mg, 0.03 mmol) in anhydrous MeOH (1.0 mL) was added NaOMe (3 mg, 0.06 mmol). The reaction mixture was stirred at r.t. for 16 h then evaporated in vacuo, re-dissolved in CH₂Cl₂ (4.0 mL) and extracted with NaHCO_3(aq.) (2 × 2.0 mL). The organic phase was dried (MgSO₄), filtered and concentrated in vacuo to give a solid that was purified by flash column chromatography (SiO₂; EtOAc/hexane = 3:7) to afford the title compound as a yellow powder (8 mg, 75%); mp 148–149 °C (see Supporting Information^S3 149–150 °C). ¹H NMR (400 MHz, CDCl₃): δ = 8.18 (dd, ³J = 8.5 Hz, ⁴J = 1.0 Hz, 1 H), 7.88 (dd, ³J = 8.0 Hz, ⁴J = 1.5 Hz, 1 H), 7.63–7.52 (m, 2 H), 7.49–7.42 (m, 1 H), 7.36–7.31 (m, 1 H), 7.30–7.23 (m, 2 H), 4.20 (t, ³J = 8.0 Hz, 2 H), 4.04 (s, 3 H), 3.55–3.47 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.0, 166.8, 158.3, 147.6, 139.2, 132.3, 131.2, 130.7, 128.9, 128.6, 127.0, 126.9, 124.9, 124.8, 123.4, 122.9, 120.9, 52.3, 51.9, 50.3, 26.9. IR (KBr): ν_max = 2945 (m), 1725 (s, C=O), 1717 (s, C=O), 1617 (m), 1597 (m), 1483 (m), 1228 (w), 754 (w) cm^–1. LRMS (ESI⁺): m/z (%) = 363 [M + H]⁺. HRMS (ESI⁺): m/z calcd for C₂₁H₁₉N₂O₄ [M + H]⁺: 363.1345; found: 363.1341.
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