Synlett 2017; 28(20): 2823-2828
DOI: 10.1055/s-0036-1589057
letter
© Georg Thieme Verlag Stuttgart · New York

Hydrogen-Bond-Promoted Friedel–Crafts Reaction of Secondary Propargylic Fluorides: Preparation of 1-Alkyl-1-aryl-2-alkynes

Jean-Denys Hamel, Meggan Beaudoin, Mélissa Cloutier, Jean-François Paquin*
Further Information

Publication History

Received: 20 April 2017

Accepted after revision: 29 May 2017

Publication Date:
06 July 2017 (eFirst)

Dedicated to Prof. Victor Snieckus on the occasion of his 80th birthday

Abstract

We report that aromatic propargylation is achievable with secondary propargylic fluorides, thus affording 1-alkyl-1-aryl-2-alkynes. In the present case, hydrogen bonding is responsible for the activation of the C–F bond. A large excess of arene nucleophile is shown to be necessary to achieve good yields.

Supporting Information

 
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  • 27 Compound 21 principally led to side reactions even under reaction conditions where HFIP was omitted, affording 2 in 29% NMR yield (o/p = 1:7.7). It should also be mentioned that 21 was also subject to rapid decomposition during column chromatography or during evaporation postpurification.
  • 28 Representative Procedure for the Friedel–Crafts Reaction of Propargylic Fluorides – Synthesis of 1-Methyl-4-(1-phenylhex-1-yn-3-yl)benzene (2) A solution of TFA (8.7 μL, 0.114 mmol) in CH2Cl2 (13 mL) was prepared. 3-(Fluorohex-1-ynyl)benzene (1, 40 mg, 0.227 mmol) was then charged in a vial and dissolved in this TFA/CH2Cl2 solution (1.3 mL, resulting in 5 mol% of TFA). Toluene (0.60 mL, 5.68 mmol) was added, followed by HFIP (0.13 mL). The resulting solution was stirred at r.t. for 18 h. The reaction was quenched with sat. NaHCO3 and stirred until no more gas evolved. It was then extracted with CH2Cl2 (3×). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The desired product (41.5 mg, 74%, o/p = 1:9.2) was isolated as a colorless oil by flash chromatography using hexanes. IR (ATR, ZnSe): ν = 2957, 2925, 2871, 1686, 1599, 1450, 1281, 812, 754, 689 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.57 (d, 0.11 H, minor, J = 7.7 Hz) 7.44–7.42 (m, 2 H), 7.31–7.24 (m, 4.89 H), 7.14 (d, 2 H, J = 7.8 Hz), 4.04 (dd, 0.11 H, minor, J = 9.1, 5.1 Hz), 3.81 (dd, 0.89 H, major, J = 8.4, 6.1 Hz), 2.39 (s, 0.32 H), 2.34 (s, 2.68 H), 1.85–1.72 (m, 2 H), 1.59–1.44 (m, 2 H), 0.99–0.93 (m, 3 H). 13C NMR (126 MHz, CDCl3): δ = 139.5, 136.3, 131.8, 130.6 (minor), 129.3, 128.3, 127.8, 127.7 (minor), 127.5, 126.7 (minor), 126.4 (minor), 124.0, 92.1, 83.1, 41.0, 39.4 (minor), 38.0, 34.7 (minor), 29.9 (minor), 21.2, 21.1 (minor), 20.8, 19.4 (minor), 14.0; ESI-HRMS: m/z calcd for C19H21[M + H]+: 249.1638; found: 249.1634