Grignard-Triggered Fragmentation of Vinylogous Acyl Triflates: Synthesis of (Z)-6-Heneicosen-11-one, the Douglas Fir Tussock Moth Sex Pheromone

Abstract

Grignard reagents react with vinylogous acyl triflates in toluene via an addition-fragmentation sequence to afford alkynyl ketones. A streamlined synthesis of (Z)-6-heneicosen-11-one, the sex pheromone of the Douglas fir tussock moth, illustrates the ­utility of this method.

synthesis - fragmentation - Douglas fir tussock moth

References and Notes

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There are more than thirty previous syntheses of 1. Selected examples and leading references:

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<A NAME="RS12405ST-7">7</A> Acyl triflate 4 (R = Tf) was prepared from 2-pentyl-1,3-cyclohexanedione using triflic anhydride and pyridine by analogy to our published procedure, see. ref. 1. ¹H NMR (300 MHz, CDCl₃): δ = 2.75 (t, J = 6.2 Hz, 2 H), 2.47 (t, J = 6.8 Hz, 2 H), 2.32 (t, J = 7.6 Hz, 2 H), 2.07 (app quint, J = 6.5 Hz, 2 H), 1.22-1.42 (m, 6 H), 0.88 (t, J = 6.8 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 197.3, 161.7, 132.3, 36.9, 31.7, 28.64, 28.65, 28.0, 23.7, 22.2, 20.6, 13.8. HRMS (CI⁺): m/z calcd for C₁₂H₁₈O₄SF₃: 315.0878; found: 315.0893

<A NAME="RS12405ST-8">8</A>

Synthesis of Alkynyl Ketone ( 5) To a stirred solution of vinylogous acyl triflate 4 [7] (100 mg, 0.32 mmol) in toluene (3 mL) at -78 °C was added n-decyl-magnesium bromide (0.31 mL, 0.93 M in Et₂O, 0.29 mmol). The reaction mixture was warmed to r.t. over 1 h, heated at 60 °C for 1.5 h, cooled to r.t., quenched with half-sat. NH₄Cl solution (10 mL), and extracted with Et₂O. The combined organic phases were washed with H₂O, dried (MgSO₄), concentrated, and purified on silica gel (elution with 1% EtOAc-hexanes) to afford alkynyl ketone 5 as an oil that solidified on standing; yield 70 mg (80%). ¹H NMR (300 MHz, CDCl₃): δ = 2.52 (t, J = 7.3 Hz, 2 H), 2.40 (t, J = 7.5 Hz, 2 H), 2.08-2.23 (m, 4 H), 1.74 (app quint, J = 7.0 Hz, 2 H), 1.43-1.64 (m, 4 H), 1.19-1.38 (m, 18 H), 0.83-0.95 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 210.9, 81.1, 79.1, 43.0, 41.3, 31.9, 31.1, 29.6, 29.5, 29.4, 29.3, 28.8, 23.9, 23.0, 22.6, 22.2, 18.7, 18.2, 14.1, 13.1. HRMS (CI⁺): m/z calcd for C₂₁H₃₉O: 307.3001; found: 307.2999.

<A NAME="RS12405ST-9">9</A>

The Pd/BaSO₄ and pyridine must be mixed before adding alkyne 5 for best results.

<A NAME="RS12405ST-10">10</A>

¹H NMR (500 MHz, CDCl₃): δ = 5.37-5.41 (m, 2 H), 2.35-2.41 (m, 4 H), 1.94-2.06 (m, 4 H), 1.63 (app quint, J =7.4 Hz, 2 H), 1.21-1.37 (m, 22 H), 0.85-0.90 (m, 6 H). HRMS (CI⁺): m/z calcd for C₂₁H₄₁O: 309.3157; found: 309.3158.

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