α-Halogenation as a Strategy to Functionalize Cyclohexa-2,4-dienones

Abstract

A facile pyridine-mediated α-halogenation approach to functionalize cyclohexa-2,4-dienones is developed. A range of reactions, including organometallic coupling protocols, have been applied on these newly obtained halogenated cyclohexa-2,4-dienones, and the results are presented herein.

Key words

cyclohexa-2,4-dienones - α-halogenation - nucleophilic chlorination - Michael addition - dearomatization - palladium hydride - conjugate reduction

• References and Notes


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• 9 General Procedure for α-Halogenation Reaction To a stirred solution of MOB 1 (100 mg, 0.54 mmol) and pyridine (0.81 mmol for α-iodination and α-bromination; 1.89 mmol for α-chlorination) in CH₂Cl₂ (4 mL) at r.t. was added iodine (0.81 mmol) or bromine (0.81 mmol as a solution in 1 mL CH₂Cl₂ or neat Br₂ in the case of naphthoquinone monoketals 7 and 8) or NCS (1.89 mmol). The resulting mixture was allowed to stir at r.t. or at reflux as indicated in the Schemes, for 15 min to 16 h before quenching with sat. Na₂S₂O₃. The layers were separated, and the organic layer was washed with brine, dried over Na₂SO₄ and concentrated in vacuo to give a residue, which was purified by column chromatography (EtOAc in hexanes, 0–15%) to afford α-iododienone 1a (96%), α-bromodienone 1b (95%), or α-chlorodienone 1c (93%). α-Iododienone 1a ¹H NMR (400 MHz, CDCl₃): δ = 7.68 (d, J = 7.6 Hz, 1 H), 5.27 (d, J = 7.6 Hz, 1 H), 3.81 (s, 3 H), 3.31 (s, 6 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 188.9 (C), 164.9 (C), 151.1 (CH), 98.1 (CH), 94.4 (C), 90.5 (C), 56.5 (CH₃), 51.8 (2 × CH₃) ppm. α-Bromodienone 1b ¹H NMR (400 MHz, CDCl₃): δ = 7.39 (d, J = 8.0 Hz, 1 H), 5.31 (d, J = 8.0 Hz, 1 H), 3.81 (s, 3 H), 3.32 (s, 6 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 187.6 (C), 163.8 (C), 143.8 (CH), 113.7 (C), 96.3 (CH), 95.3 (CH), 56.4 (CH₃), 51.7 (2 × CH₃) ppm. α-Chlorodienone 1c ¹H NMR (400 MHz, CDCl₃): δ = 7.14 (d, J = 7.6 Hz, 1 H), 5.33 (d, J = 7.6 Hz, 1 H), 3.80 (s, 3 H), 3.31 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 187.5 ( C), 162.9 (C), 139.8 (CH ), 123.2( C), 95.4 (C), 95.2 (CH ), 56.3 (CH₃ ), 51.6 (2 × CH₃).
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